Publications by Type: Journal Article

An underwater geomorphological survey along the coasts of six Cycladic islands (Sifnos, Antiparos, Paros, Naxos, Iraklia and Keros) revealed widespread evidence of a recent 30–40 cm submergence, part of which may have seismic origin. Comparison with information reported from earthquakes having affected the area suggests that at least part of the recent submergence might be an effect of the 1956 Amorgos earthquake. Modelling of the co-seismic and short-term post-seismic effects of the earthquake revealed that part of the observed subsidence may be explained in some of the islands by a fast post-seismic relaxation of a low-viscosity layer underlying the seismogenic zone. However far-field observations are underestimated by our model, and may be affected by a wider deformation field induced by the largest aftershock of the Amorgos sequence, or by other earthquakes.

VFTS 682, a very massive and very hot Wolf-Rayet (WR) star recently discovered in the Large Magellanic Cloud near the famous star cluster R136, might be providing us with a glimpse of a missing link in our understanding of Long Gamma-Ray Bursts (LGRBs), including dark GRBs. It is likely its properties result from chemically homogeneous evolution (CHE), believed to be a key process for a massive star to become a GRB. It is also heavily obscured by dust extinction, which could make it a dark GRB upon explosion. Using Spitzer data we investigate the properties of interstellar dust in the vicinity of R136, and argue that its high obscuration is not unusual for its environment and that it could indeed be a slow runaway (``walkaway'') from R136. Unfortunately, based on its current mass loss rate, VFTS 682 is unlikely to become a GRB, because it will lose too much angular momentum at its death. If it were to become a GRB, it probably would also not be dark, either escaping or destroying its surrounding dusty region. Nevertheless, it is a very interesting star, deserving further studies, and being one of only three presently identified WR stars (two others in the Small Magellanic Cloud) that seems to be undergoing CHE.

Kidney impairment (KI) at the time of initial diagnosis is common in myeloma. The improvement of kidney function and the reversal of KI are of utmost importance. Recent advances have made it possible to reverse acute kidney damage due to myeloma in most patients, at least if treatment is immediately implemented. Immediate antimyeloma therapy and appropriate hydration are the most commonly used treatment modalities for the management of acute KI related to myeloma. Mechanical approaches can only temporarily reduce the free light-chain load, and without effective chemotherapy they are probably not able to significantly improve kidney function. However, the role of mechanical approaches together with effective chemotherapy is still being explored. Thalidomide, lenalidomide, and bortezomib have improved the survival of myeloma patients, but they have also improved the outcome of patients presenting with KI. Thalidomide is safe to use on patients with KI without dose adjustments. Lenalidomide needs dose modification, but it can improve kidney function in many patients. Bortezomib seems to be the agent of choice for most patients presenting with KI without dose modifications. This review focuses on the management of patients presenting with "myeloma kidney" using modern chemotherapy approaches, especially novel agents. © 2012 National Kidney Foundation, Inc.

The study attempts to develop an outpatient service quality scale by investigating the key dimensions which assess parental satisfaction and provides a recommendation on an improved health service delivery system. The survey was conducted in an Ear-Nose-Throat outpatient clinic of a Greek public pediatric hospital. A total of 127 parents in outpatient waiting areas were chosen; 74.8% of the sampled parents were under 40, and 78% were mothers. A factor analysis was performed; while a Fischer's exact test and multinomial logistic regression analysis was conducted. All Cronbach's α exceeded 0.70 and all factor loadings exceeded 0.50. Twenty-three items were retained through the scale development process and seven factors were formed that appear to be statistically valid and clinically meaningful: access and convenience, doctor's attention, customization, reliability, assurance, satisfaction and loyalty. Findings were discussed in relation to parents' overall satisfaction and intention of reusing and recommending outpatient clinic. Satisfaction was found to be positively affected by access and convenience and doctors' attention. Staff attitude and the telephone procedure of scheduling the child's examination found positively correlated to the likelihood of recommending services to friends and relatives. Time and communication in the waiting room influenced parents' satisfaction. Overall, results reveal the measures that need to be taken in order to improve outpatient service quality. © 2011 Elsevier Ltd.

Study Objective: The purpose of this study was the recording of physical activity and sedentary habits of adolescents with polycystic ovarian syndrome (PCOS). Methods: We performed a structured interview to assess the level of physical activity and sedentary habits of girls with PCOS. We used a group of healthy adolescents as controls. All girls had their age, height, weight, hip and waist circumference measured and their BMI calculated. Results: 81 girls (35 with PCOS and 46 controls) participated in the study. Girls with PCOS engaged in physical activities less than controls. Even when they did, the frequency and intensity of exercise was less. Also, girls with PCOS were less likely to be aware of the positive effects of exercise on their health. Girls in both groups were sedentary in excess of the 4 hours per day limit, which has been linked with obesity. Conclusion: Healthy teenagers were involved in a sporting activity more often and more frequently than the PCOS group. Athletic and sedentary habits of adolescents with PCOS may interact with other factors leading to obesity. © 2012 North American Society for Pediatric and Adolescent Gynecology.

It is well known that low-dose metronomic chemotherapy has antiangiogenic activity. The aim of the present trial was to investigate the antiangiogenic properties of weekly docetaxel in patients with metastatic breast cancer. In total, 157 metastatic breast cancer patients received 35 mg/m 2 docetaxel weekly as a recommended treatment. Blood samples were collected before the start of chemotherapy (baseline) and during treatment. Nitric oxide (NO) and vascular endothelial growth factor A (VEGF-A) plasma levels were measured at baseline and during treatment, while VEGF-A, endothelial nitric oxide synthase (eNOS) and thrombospondin-1 (THBS-1) peripheral blood mRNA levels were measured at baseline, in 127 patients and 39 female healthy controls. In general, the treatment was well-tolerated. Sixty-one patients (38%) achieved an objective response (4% complete and 34% partial response), while 52 (33%) had stable disease and 27 (17%) progressed. At a median follow-up of 33.5 months (range 2.8-45.0), 118 patients (74%) demonstrated disease progression and 94 (59%) had died. Median progression-free survival (PFS) was 8.8 months and median overall survival (OS) was 27.7 months. Median baseline level of plasma NO was significantly lower in patients than in healthy controls (p=0.010), while none of the plasma markers significantly changed upon docetaxel treatment. In addition, the median relative quantification value for THBS-1 mRNA was significantly higher (p<0.001) in patients as compared to healthy controls. NO plasma levels were positively associated with the number of organs involved (p=0.008). In multivariate analysis, low eNOS mRNA levels showed adverse prognostic significance for OS and high THBS-1 mRNA levels were found to be associated with shorter OS and PFS, independently from established clinical prognostic factors. Although an antiangiogenic activity of weekly docetaxel was not demonstrated in the present study, some interesting observations regarding the prognostic role of a number of blood angiogenic markers could be made.

We present an overview of recent advances within the field of slow- and stopped-light in metamaterial and plasmonic waveguides. We start by elucidating the mechanisms by which these configurations can enable complete stopping of light. Decoherence mechanisms may destroy the zero-group-velocity condition for real-frequency/complex-wavevector modes, but we show that metamaterial and nanoplasmonic waveguides also support complex-frequency/real-wavevector modes that uphold the light-stopping condition. A further point of focus is how, by using gain, dissipative losses can be overcome in the slow- and stopped-light regimes. To this end, on the basis of full-wave finite-difference time-domain (FDTD) simulations and analytic transfer-matrix calculations, we show that the incorporation of thin layers made of an active medium, placed adjacently to the core layer of a negative-refractive-index waveguide, can fully remove dissipative losses in a slow- or stopped-light regime where the effective index of the guided lightwave remains negative. © 2012 Elsevier B.V. All rights reserved.

BACKGROUND AND AIMS: Caregivers of patients with schizophrenia experience increased levels of psychological distress. This study investigated the impact of caring for patients with chronic schizophrenia on the mental health status of the caregivers and described the relationship between various socio-demographic and clinical characteristics and caregiving psychological distress.\n\nMETHODS: The study was carried out at the Psychiatric Hospital of Athens. The Symptom Check List Revised (SCL-90-R) was administered to 87 caregivers of chronic schizophrenia patients and 90 healthy controls. The Positive and Negative Syndrome Scale (PANSS) was administered to schizophrenia patients in order to assess illness severity.\n\nRESULTS: The group of caregivers scored higher on the majority of symptom dimensions of the SCL-90-R than the control group. Clinical features of schizophrenia, i.e. duration of illness and PANSS positive and negative symptoms significantly predicted caregiving psychological distress. Caregivers' and patients' socio-demographic characteristics were not associated with caregivers' distress, with the exception of caregivers' sex: female caregivers experienced significantly higher levels of psychological distress than males.\n\nCONCLUSIONS: The study suggests that clinical features of schizophrenia influence distress levels in caregivers of patients with chronic schizophrenia. The stronger predictors of distress appear to be female caregiver's gender, duration of illness as well as positive and negative symptomatology.

ABSTRACT: The FAST project (Food Allergy Specific Immunotherapy) aims at the development of safe and effective treatment of food allergies, targeting prevalent, persistent and severe allergy to fish and peach. Classical allergen-specific immunotherapy (SIT), using subcutaneous injections with aqueous food extracts may be effective but has proven to be accompanied by too many anaphylactic side-effects. FAST aims to develop a safe alternative by replacing food extracts with hypoallergenic recombinant major allergens as the active ingredients of SIT. Both severe fish and peach allergy are caused by a single major allergen, parvalbumin (Cyp c 1) and lipid transfer protein (Pru p 3), respectively. Two approaches are being evaluated for achieving hypoallergenicity, i.e. site-directed mutagenesis and chemical modification. The most promising hypoallergens will be produced under GMP conditions. After pre-clinical testing (toxicology testing and efficacy in mouse models), SCIT with alum-absorbed hypoallergens will be evaluated in phase I/IIa and IIb randomized double-blind placebo-controlled (DBPC) clinical trials, with the DBPC food challenge as primary read-out. To understand the underlying immune mechanisms in depth serological and cellular immune analyses will be performed, allowing identification of novel biomarkers for monitoring treatment efficacy. FAST aims at improving the quality of life of food allergic patients by providing a safe and effective treatment that will significantly lower their threshold for fish or peach intake, thereby decreasing their anxiety and dependence on rescue medication.

BACKGROUND: Accumulating evidence suggests the potential superiority of office aortic blood pressure (BP) over brachial in the management of arterial hypertension. The noninvasive aortic 24-h ambulatory brachial BP monitoring (ABPM) is potentially the optimal method for assessing BP profile. The objective of the present study was to investigate the feasibility and reproducibility to perform noninvasively 24-h aortic ABPM with a novel validated brachial cuff-based automatic oscillometric device (Mobilo-O-Graph) which records brachial BP and waveforms and assesses aortic BP via mathematical transformation. METHODS: Thirty consecutive subjects (mean age: 53.6 ± 11.6 years, 17 men) had a test-retest ABPM with at least 1-week interval. No modification of vasoactive drug treatment during the interval was allowed while similar 24-h activity during both recording days was recommended. RESULTS: The average number of valid readings for brachial vs. aortic BP were 69.9 ± 10.4 vs. 58.0 ± 13.3 in the initial 24-h assessment (P < 0.001) and 68.3 ± 10.8 vs. 56.4 ± 13.6 in the repeat assessment (P < 0.001). No differences in average 24 h aortic BP values were observed between the two assessments (systolic blood pressure (SBP) 115.9 ± 7.7 vs. 115.1 ± 6.0 mm Hg, respectively, P = 0.48, and diastolic 79.7 ± 7.4 vs. 79.2 ± 8.7, P = 0.54). Reproducibility indices of aortic pressure including, intraclass coefficient of variation (SBP: 0.80 (95% confidence interval 0.58-0.90); diastolic: 0.92 (0.83-0.96)) and s.d. of differences (SBP/diastolic: 6.0/4.5 mm Hg) indicated acceptable reproducibility. The Bland-Altman plots indicated no evidence of systemic bias. CONCLUSIONS: In conclusion, these data suggest that noninvasive 24-h ABPM is feasible and provides reproducible values. Future studies should validate the prognostic ability of 24-h aortic hemodynamics.

In this work, artificial neural networks (ANNs) were developed and applied in order to forecast the discomfort levels due to the combination of high temperature and air humidity, during the hot season of the year, in eight different regions within the Greater Athens area (GAA), Greece. For the selection of the best type and architecture of ANNs-forecasting models, the multiple criteria analysis (MCA) technique was applied. Three different types of ANNs were developed and tested with the MCA method. Concretely, the multilayer perceptron, the generalized feed forward networks (GFFN), and the time-lag recurrent networks were developed and tested. Results showed that the best ANNs type performance was achieved by using the GFFN model for the prediction of discomfort levels due to high temperature and air humidity within GAA. For the evaluation of the constructed ANNs, appropriate statistical indices were used. The analysis proved that the forecasting ability of the developed ANNs models is very satisfactory at a significant statistical level of p < 0. 01. © 2012 Springer-Verlag.

The number of options available to drug discovery scientists to enhance the solubility of poorly soluble compounds by conventional formulation approaches is limited. In most cases, drug formulation is oriented toward the creation of a supersaturated solution upon contact with aqueous environment, often combined with solubilizing agents and precipitation inhibitors. The most popular formulations for achieving this target are the lipid-based formulations called self-emulsifying and self-microemulsifying drug delivery systems, SEDDS and SMEDDS, respectively. They offer enhanced absorption and hence enhanced oral bioavailability of lipophilic drugs, presenting the drug in solubilized form in vivo, avoiding dissolution, which can be the rate limiting step in drug absorption for sparingly soluble drugs. The production of high energy or rapid dissolving solid state formulations using drug particle engineering to enhance drug solubility and bioavailability is also applied. These formulations include solid dispersions, nanoparticles, co-ground mixtures etc. Furthermore, the development of prodrugs is also a useful strategy to improve the physicochemical, biopharmaceutical or pharmacokinetic properties of pharmacologically potent compounds, and thereby increase the developability and usefulness of a potential drug. Up to now, most medications were made for adults and children's requirements were not taken into account. Since the recent adoption of Paediatric Regulations in the U.S. and E.U., there is a greater demand for age-appropriate medicines for children. The challenges in paediatric formulation development are mostly associated with the difficulty in defining design requirements for the intended dosage form that is most appropriate for the target patient population, due to the diversity of the paediatric population (range of ages, physical size and capabilities) that varies significantly from birth to age 12 yrs old along with the dosage flexibility. The last years there has been an effort to develop solid paediatric formulations that deliver the appropriate dose in a ``user friendly{''} way and to find alternative drug delivery vehicles, such as mini-tablets, dairy products, and new taste masking techniques in order to improve drug acceptability. In addition, alternative routes of administration have been proposed such as inhalation and nasal administration.

TiO 2 nanotubular (NT) membranes with bundle shape morphology were prepared by rapid breakdown anodization (RBA) in fluorine free aqueous electrolytes. The self-assembled nanotube-like materials were detached from the metal foil by immersion in methanolic Br 2 solution and the free-standing membranes were successfully transferred on top of transparent conductive electrodes modified by freshly prepared nanoparticulate (NP) titania films. The composite electrodes, after post-annealing at 450°C, were crystallized under the anatase polymorphism and, then, effectively sensitized by the standard N719 dye (confirmed by micro-Raman spectroscopy under Resonance conditions). The resulting photoelectrodes were incorporated in dye-sensitized solar cells (DSCs) enabling front-side illumination (FSI). The fabricated DSCs attained overall photovoltaic conversion efficiencies of the order of 4.6% under 1 sun (AM 1.5) illumination. The relatively high performance was mainly attributed to the successful packing of the two (NT and NP) layers creating a low resistance interface as well as to the favourable electron transport/recombination dynamics that govern these solar cells. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Gaia-ESO Public Spectroscopic Survey has begun and will obtain high quality spectroscopy of some 100000 Milky Way stars, in the field and in open clusters, down to magnitude 19, systematically covering all the major components of the Milky Way. This survey will provide the first homogeneous overview of the distributions of kinematics and chemical element abundances in the Galaxy. The motivation, organisation and implementation of the Gaia-ESO Survey are described, emphasising the complementarity with the ESA Gaia mission. Spectra from the very first observing run of the survey are presented.

Human rhinoviruses are single stranded positive sense RNA viruses that are presented in more than 50% of acute upper respiratory tract infections. Despite extensive studies on the genetic diversity of the virus, little is known about the forces driving it. In order to explain this diversity, many research groups have focused on protein sequence requirements for viable, functional and transmissible virus but have missed out an important aspect of viral evolution such as the genomic ontology of the virus. This study presents for the first time the genomic signature of 111 fully sequenced HRV strains from all three groups HRV-A, HRV-B and HRV-C. We observed an HRV genome tendency to eliminate CpG and UpA dinucleotides, coupling with over-representation of UpG and CpA. We propose a specific mechanism which describes how rapid changes in the HRV genomic sequence can take place under the strict control of conservation of the polypeptide backbone. Moreover, the distribution of the observed under- and over-represented dinucleotides along the HRV genome is presented. Distance matrice tables based on CpG and UpA odds ratios were constructed and viewed as heatmaps and distance trees. None of the suppressions can be attributed to codon usage or in RNA secondary structure requirements. Since viral recognition is dependent on RNA motifs rich in CpG and UpA, it is possible that the overall described genome evolution mechanism acts in order to protect the virus from host recognition.

This paper identifies and analyses the geopolitical impact that the Syrian crisis has on Lebanon. This impact is manifested in two forms: a subsystemic one (within the Syria-Lebanon subsystem) and a systemic one (exerted from the system of the wider Middle East). The first refers to the direct repercussions that the increasing instability of the Syrian part has on the Lebanese part of the subsystem. More specifically, the impact that have some factors of the Syrian crisis –namely, increasing sectarianism and Islamic radicalism- on the internal political and religious power relations of Lebanon. The second form of impact refers to the indirect yet critical repercussions that the instability at the centre of the Middle Eastern system has on Lebanon. As a state of proxy actors through which the regional powers project power and as an integral part of the Syria-Lebanon subsystem, Lebanon is the primary point on which the systemic pressure is applied. As a result of this systemic impact, the internal political-religious power relations of Lebanon become a micro-level representation of the regional power relations of the wider Middle Eastern system.

A systematic study, by means of full electrodynamic calculations, of the optical activity of layer-by-layer chiral crystals of finite silver nanorods is presented. The nature of the eigenmodes of the electromagnetic field and the formation of partial gaps for a specific circular polarization in these crystals are analyzed by reference to the hybrid plasmon modes of the structural basis of twisted nanorods. It is shown that collective plasmon modes of the helical assembly give rise to giant optical activity effects, which persist for any angle of incidence and polarization direction. The effects, which are robust against the twisting angle and become more pronounced with increasing particle concentration, can be tuned within a broad range of frequencies in the infrared and visible spectrum by appropriately choosing the rod length. Potential applications of these structures for polarization control in subwavelength optical components are anticipated.

A systematic study, by means of full electrodynamic calculations, of the optical activity of layer-by-layer chiral crystals of finite silver nanorods is presented. The nature of the eigenmodes of the electromagnetic field and the formation of partial gaps for a specific circular polarization in these crystals are analyzed by reference to the hybrid plasmon modes of the structural basis of twisted nanorods. It is shown that collective plasmon modes of the helical assembly give rise to giant optical activity effects, which persist for any angle of incidence and polarization direction. The effects, which are robust against the twisting angle and become more pronounced with increasing particle concentration, can be tuned within a broad range of frequencies in the infrared and visible spectrum by appropriately choosing the rod length. Potential applications of these structures for polarization control in subwavelength optical components are anticipated.

There is emerging evidence that oral mucositis/stomatitis is a common adverse effect of sunitininb antiangiogenic therapy in patients with metastatic renal cell carcinoma (mRCC). In addition, a case of sunitinib-related jaw osteonecrosis was recently described. We report on 2 patients with mRCC treated with sunitinib. The first patient, a 19-year-old woman, treated with cisplatin and sunitinib, presented with oral pain, malodor, spontaneous and continuous gingival bleeding, and painful necrotic ulcerations clinically resembling necrotizing ulcerative gingivitis (NUG). Suntinib-related stomatitis and bleeding were considered cumulative to NUG symptoms. The second patient, a 64-year-old woman, treated with sunitinib only, complained of mandibular pain. Sunitinib-related jaw osteonecrosis was diagnosed. Gingival bleeding and soft tissue necrosis, as well as jaw osteonecrosis may develop as adverse events of sunitinib use. Antiangiogenic therapies are increasingly used in the treatment of cancers. The presented cases are aimed to alert health care professionals on adverse oral events. © 2012 Elsevier Inc. All rights reserved.

The recent rise in global sea level is causing the disappearance of an important geomorphological sea-level indicator, the tidal notch.Tidal notches have often been used in carbonate coasts for Quaternary and late Holocene sea-level reconstructions and estimation of tectonic movements, especially in uplifting areas. In this paper, we review the rates of tidal notch development, and examine the recent gradual depletion of this feature, during at least the last century, and its relation to the increasing rates of sea-level rise. Some examples of tidal notch development are provided with fossil submerged notches from Greece. Although tidal notches are no longer forming in the present-day mid-littoral zone, underwater marks on carbonate cliffs may still provide evidence of submerged tidal notches corresponding to former sea-level positions, or of recent vertical shoreline displacements of seismic origin.

Glycosaminoglycans are natural heteropolysaccharides that are present in every mammalian tissue. They are composed of repeating disaccharide units that consist of either sulfated or non-sulfated monosaccharides. Their molecular size and the sulfation type vary depending on the tissue, and their state either as part of proteoglycan or as free chains. In this regard, glycosaminoglycans play important roles in physiological and pathological conditions. During recent years, cell biology studies have revealed that glycosaminoglycans are among the key macromolecules that affect cell properties and functions, acting directly on cell receptors or via interactions with growth factors. The accumulated knowledge regarding the altered structure of glycosaminoglycans in several diseases indicates their importance as biomarkers for disease diagnosis and progression, as well as pharmacological targets. This review summarizes how the fine structural characteristics of glycosaminoglycans, and enzymes involved in their biosynthesis and degradation, are involved in cell signaling, cell function and cancer progression. Prospects for glycosaminoglycan-based therapeutic targeting in cancer are also discussed.

Placement of peripherally inserted central catheters (PICCs), definitely offers a clear advantage over any other method regarding central venous catheterization. Its ultrasonographic orientation enhances significantly its accuracy, safety and efficacy, making this method extremely comfortable for the patient who can continue his or her therapy even in an outpatient basis. We present the first reported case of a PICCS insertion in Greece, which has been performed by a university-degree nurse. The aim of this review of literature was to present the evolution in nursing practice in Greece. A PICC was inserted in a 77-year-old male patient suffering from a recent chemical pneumonia with a history of Alzheimer's disease. A description of all the technical details of this insertion is reported, focusing on the pros and cons of the method and a thorough review of the history and advances in central venous catheterization throughout the years is also presented. PICCs provide long-term intravenous access and facilitate the delivery of extended antibiotic therapy, chemotherapy and total parenteral nutrition. We strongly believe that PICCs are the safest and most effective method of peripherally inserted central venous catheterization. Larger series are necessary to prove the above hypothesis, and they are under construction by our team.

We report on the optical properties of a layer-by-layer structure of silver nanorods, with their axes aligned perpendicular to the z direction and mutually twisted through an angle of 60° from layer to layer, by means of rigorous full electrodynamic calculations using the layer-multiple-scattering method, properly extended to describe axis-symmetric particles with arbitrary orientation. We analyze the complex photonic band structure of this crystal in conjunction with relevant polarization-resolved transmission spectra of finite slabs of it and explain the nature of the different eigenmodes of the electromagnetic field in the light of group theory. Our results reveal the existence of sizable polarization gaps and demonstrate the occurrence of strong optical activity and circular dichroism, combined with reduced dissipative losses, which make the proposed architecture potentially useful for practical applications as ultrathin circular polarizers and polarization rotators.

Abstract Despite the initial enthusiasm following the discovery of the association of BRCA germline mutations with hereditary breast and/or ovarian cancer, in many families affected by the syndrome no pathogenic mutations were detected in the two genes, although exhaustively searched. Many other genes have also been implicated due to their role in the same pathway of DNA repair where the BRCA1/2 genes are involved: homologous recombination (HR). Among them, PALB2 clearly emerges as the third breast cancer susceptibility gene. Its mutations have been detected in most populations investigated so far, albeit rarely: in 1%-4% of families negative for BRCA mutations, with either partial or complete penetrance. In some populations, PALB2 recurrent mutations have been identified and the estimated hazard risks are comparable to those of BRCA mutations. Since new effective targeted therapeutic options are becoming available ("synthetic lethality" with novel PARP inhibitors, etc.) that are applicable to all those patients with a defect in HR pathway, it is imperative to detect all these candidate patients. Data obtained from laboratory tests in the tumor (simple immunohistochemistry, gene expression analysis, etc.) can assist in the recognition of a specific pattern (BRCA1ness, HRless) so that even patients that look "sporadic" could benefit from these targeted therapies. Therefore, a genetic analysis algorithm is proposed, although with the advent of Next Generation Sequencing it is predicted that in the future most germline genetic alterations and also somatic or epigenetic events in the tumor of these genes will be detected

In order to examine the genetic variation of clinical and food isolates of Listeria monocytogenes in Greece, a total of 61 L. monocytogenes non-duplicate isolates, recovered from clinical specimens (n=19) and food (n=42), were serotyped and genotyped using two different Random Amplification of Polymorphic DNA (RAPD) protocols and Multiple Locus Variable Number Tandem Repeat Analysis (MLVA). Serotype group 4b, 4d, 4e prevailed (39.4%), among both clinical and food isolates, followed by serotype group 1/2a, 3a (23.0%), which nevertheless was detected only among food isolates. The most discriminatory typing protocol was MLVA, which grouped four isolates into two pairs, while the remaining isolates produced unique fingerprints. Similar results were obtained when taking into account the combination of the two RAPD protocols (Simpson index 0.999); six isolates were grouped into three pairs, two of which were the pairs that were identified also by MLVA. Single use of each RAPD protocol resulted in inferior discrimination (Simpson index 0.978 and 0.997, respectively). In conclusion, the two molecular procedures, MLVA, and the combined RAPD protocols, produced similar results, showing that L. monocytogenes isolates from clinical and food specimens were highly heterogenous and that clustering was very uncommon.

Objective: Apart from the effects of a dysfunctional thyroid gland on the cardiovascular system, thyroid function within the reference range may have an impact on the vasculature. The present study aimed to evaluate the association between thyroid function and markers of arterial structure and function in euthyroid postmenopausal women. Methods: The present cross-sectional study recruited 106 healthy postmenopausal women with a mean age of 55.0 years and thyroid-stimulating hormone (TSH) levels within the laboratory reference range (0.4-4.5 μIU/ml). Anthropometric and biochemical measures as well as blood pressure were determined in each individual. Vascular structure and function were assessed by intima-media thickness, pulse wave velocity (PWV), augmentation index and flow-mediated dilation, respectively. We evaluated the associations between arterial markers and serum TSH, free triiodothyronine, free thyroxin, as well as serum thyroid peroxidase and thyroglobulin autoantibodies. Results: Mean levels of PWV increased linearly across increasing TSH quartiles (P value = 0.014). Individuals with serum TSH greater than 2.5 μIU/ml had significantly higher values of PWV when compared with individuals with TSH levels below 2.5 μIU/ml (9.68 ± 1.97 vs. 8.54 ± 1.83 m/s; P = 0.030). In multivariate analysis, age, insulin resistance and TSH above 2.5 μIU/ml were the only significant predictors of PWV (TSH, β-coefficient = 0.222; P = 0.014). No associations were found between the remaining markers and levels of thyroid hormones, whereas thyroid antibodies were not associated with any of the arterial markers. Conclusion: Women with TSH levels in the upper reference range have increased arterial stiffness compared to women with lower TSH. The upper limit of normal TSH in postmenopausal women may need re-evaluation with respect to the effects on the vasculature. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

PURPOSE: This study evaluated the level of histamine in the interaction between the environment and the visual system during lifespan development, exploring potential sex differences. METHODS: Male and female Wistar rats, reared in standard laboratory or enriched-environment cages from birth to prepuberty or adulthood, were sacrificed during the critical period for visual development at postnatal day (P) 25 (P25) or in adulthood at P90. Additionally, animals born in standard conditions were exposed to an enriched environment at P90 and sacrificed at P150. The optic chiasm and the visual cortex were dissected out and tissue histamine was quantified fluorophotometrically. Statistical analyses were performed by ANOVA. RESULTS: Histamine levels in the optic chiasm were higher in male than in female rats at all ages. Comparable sex differences in the visual cortex were observed only during prepuberty. Basal histamine content in the optic chiasm was higher in prepuberty and decreased in adulthood in a sex-independent manner. Exposure to an enriched environment decreased optic chiasm histamine levels in both sexes and resulted in no sex difference in the cortical histamine levels at any age. Increased amine levels were detected in the optic chiasm of female rats exposed to an enriched environment during adulthood. CONCLUSIONS: This study presents first evidence associating central histamine levels with the visual system development and environmental adaptation, thus providing the lead for the investigation of the hitherto elusive role of histamine in the regulation of visual processes. Furthermore, the findings challenge the impact of laboratory animal raising environments in developmental and behavioral studies.

Detailed mapping along the northwestern coastline of Euboea has provided new evidence of colonization by Lithophaga lithophaga (L.) reaching about 3.8 m above the present biological MSL. Such marine biological marks, together with morphological notches, correspond to the occurrence of two sequences of Holocene vertical displacements higher than those reported by previous studies, on the central part of the southern coast and along the northern coast of the island. A well developed emerged notch is found at + 1.7 ± 0.1 m above present mean sea level, whereas the uppermost part of the lithophagid holes suggest a former emerged shoreline at least at + 3.8 ± 0.1 m. Radiocarbon AMS dating of Lithophaga shells found in their burrows, showed that the lower uplifted shoreline corresponds to a tectonic event (probably coseismic) apparently dated at 2200 a BP, while the higher shoreline corresponds to an older relative sea-level transgression, possibly of tectonic origin, apparently dated about 5570 a BP. The apparent radiocarbon age of lithophagid shells can be about 350 to 400 years older than the uplift event that exposed them, due to incorporation of host-rock carbon. Nevertheless, the two new paleoshorelines provide evidence that repeated uplift movements, greater than those reported by previous authors, occurred during the late Holocene, uplifting the western part of the island.

Naxos Island is situated in the Cycladic plateau (middle Aegean Sea) and consists of concaved beach zones separated by small headlands. This study investigates the diachronic palaeo-shoreline shift due to the sea level change and its effect to the palaeo-environmental evolution of the western coastal part of Naxos Island during the Late Holocene. For this purpose, six boreholes were drilled and dated using radiocarbon techniques. The associated geomorphological, sedimentological and paleontological investigation concluded that during Late Holocene, the embayments of Naxos western coastal part were frequently exposed, and their communication with the sea was not perennial. The coastal area was wider with many active lagoons and embayment changing from shallow marine environment to coastal environment frequently alternating to brackish mesohaline one. The former sea-level position in western Naxos island should be between −1.5 m and −2 m during the last 2000 years, which may partly reflect eustatic processes and partly a gradual or coseismic land subsidence.

Neutropenia is a hematologic adverse event characterized by an absolute neutrophil count (ANC) lower than 1500 cells/mL. This reduction may be due to decreased neutrophil production, accelerated use, a shift in compartments of neutrophils, or a combination of these factors. Neutropenia is often associated with infections, which are major causes of morbidity and mortality in patients with cancer. In patients with multiple myeloma, the novel agents thalidomide, lenalidomide, and bortezomib have improved outcome, but chemotherapy-related neutropenia should be carefully considered. Chemotherapy-related high-risk factors for severe neutropenia include regimens with an expected neutropenia rate of > 50%, such as the 3-drug combinations including lenalidomide plus alkylating agents or doxorubicin, whereas low-risk regimens include combinations of the novel agents with dexamethasone alone. Patient characteristics, disease stage, type of current and previous treatment, and ANC < 1000 cells/mL at baseline are additional factors that define the risk of severe neutropenia. Granulocyte-colony stimulating factor (G-CSF) should be used to manage chemotherapy-related neutropenia so that patients may stay on treatment for a longer time and benefit from it. Primary G-CSF prophylaxis should be used when high-risk regimens are administered or when low/intermediate-risk regimens are used and additional risk factors are present. Reactive G-CSF treatment is indicated when patients undergoing low-risk chemotherapy experience grade 3/4 neutropenia. If ANC restores to > 1000 cells/mL, therapy can be resumed with no dose modifications. In case of persistence of severe neutropenia, treatment should be delayed until ANC reaches > 1000 cells/mL, and dose reductions are necessary. © 2012 Elsevier Inc. All rights reserved.

This case control study aims to investigate the role of HSP90 Gln488His (C > G), HSP70-2 P1/P2, HIF-1 alpha C1772T and HSPA8 intronic 1541-1542delGT polymorphisms as potential risk factors and/or prognostic markers for breast cancer. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy cases were recruited. The above mentioned polymorphisms were genotyped; multivariate logistic regression was performed. HSP90 GG (His/His) genotype was associated with elevated breast cancer risk. Similarly, the allele dose-response model pointed to increase in breast cancer risk per G allele. HSP70-2 P1/P2, HSPA8 intronic 1541-1542delGT and HIF-1 alpha polymorphisms were not associated with breast cancer risk, as evidenced by the dose-response allele models. The positive association between HSP90 G allele and breast cancer risk seemed to pertain to both premenopausal and postmenopausal women. With respect to survival analysis, none of the aforementioned polymorphisms was associated with either disease-free survival or overall survival. HSP90α Gln488His polymorphism seems to be a risk factor for breast cancer. On the other hand, our study did not point to excess risk conferred by HSPA8 1541-1542delGT, Hsp70-2 P1/P2 and HIF-1α C1772T.

This case-control study aims to investigate the role of HTERT MNS16A polymorphism as a potential risk factors and/or a prognostic marker for breast cancer. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy controls were recruited. HTERT MNS16A polymorphism was genotyped (L: long allele, S: short allele); multivariate logistic regression was performed. No significant association was noted either at the overall analysis (OR = 1.57, 95 % CI 0.84-2.93 for heterozygous LS carriers; OR = 1.02, 95 % CI 0.54-1.95 for homozygous SS carriers) or at the subanalyses in premenopausal and postmenopausal women. With respect to survival analysis, HTERT MNS16A polymorphism was not associated with either disease-free survival or overall survival. HTERT MNS16A polymorphism does not seem to be a risk factor for breast cancer in the Caucasian Greek population. Further, larger studies from other countries and subjects seem to be needed as this novel polymorphism is being examined in depth.

Purpose: Adolescents are a vulnerable group with regard to sexually transmitted infections, including Human Papilloma Virus (HPV). This is thought to be both because of their more liberal sexual behavior and also the relative immaturity of their genital tract. The aim of the study was to examine trends in HPV infection among sexually active adolescents attending for a sexual health screen. Methods: Sexually active adolescents were offered cervical screening, HPV typing and conventional genital cultures as part of a sexual health prevention protocol. Participating adolescents also completed a sexual health questionnaire. Results: Between January 2008 and July 2011, 149 sexually active girls were examined for reproductive health issues (mean age 17.3 years). 62 (42{%}) tested positive for HPV DNA, 30 were infected by multiple types and 54 had at least one high risk type identified. The most commonly identified HPV DNA was for low risk type 42 (15 cases, 7.8{%}), followed by high risk types 51 (14 cases, 7.3{%}) and 59 (11 cases, 5.7{%}). E6-E7 mRNA expression was detected in 16 girls (11{%}), of which half were for HPV 16. Girls who tested positive for HPV DNA and mRNA had similar age at sexual debut with those that tested negative (15.1 years in all groups) but had on average more sexual partners (4.1 vs1.9 p = 0.007). Only 9 girls in this cohort had been vaccinated against HPV. Approximately half of the girls reported using inadequate or no contraception. Conclusions: HPV infection rate was high in our sample. Furthermore a high percentage was infected with high risk types and a proportion of girls demonstrated mRNA HPV expression. As age at first sexual intercourse drops, vaccination against HPV and sexual education should be instituted in early adolescence, in order to reduce long term reproductive sequelae of unsafe sexual practices. © 2012 Elsevier Inc. All rights reserved.

A large proportion of vaginal and vulvar squamous cell carcinomas (SCCs) and intraepithelial neoplasias (VAIN and VIN) are associated with HPV infection, mainly type 16. The purpose of this study was to identify HPV genotypes, as well as E6/E7 mRNA expression of high-risk HPVs (16, 18, 31, 33, and 45) in 56 histology samples of VAIN, VIN, vaginal, and vulvar SCCs. HPV was identified in 56 of VAIN and 50 of vaginal SCCs, 71.4 of VIN and 50 of vulvar SCCs. E6/E7 mRNA expression was found in one-third of VAIN and in all vaginal SCCs, 42.9 of VIN and 83.3 of vulvar SCCs. Our data indicated that HPV 16 was the commonest genotype identified in VAIN and VIN and the only genotype found in SCCs of the vagina and vulva. These findings may suggest, in accordance with other studies, that mRNA assay might be useful in triaging lesions with increased risk of progression to cancer. Copyright © 2012 Elpida Tsimplaki et al.

A transmission-line model is reformulated and combined with field theory to study the propagation characteristics in coaxial waveguides with wedge-shaped corrugations, either on the outer wall or the inner conductor. Numerical results show that this equivalent-circuit approach is in agreement with conventional full-wave methods presented in the literature. Additionally, this formulation overcomes numerical issues in the calculation of higher order Bessel functions, which usually conscript sophisticated expansion techniques.

Using the crystal structure of the uracil transporter UraA of Escherichia coli, we constructed a 3D model of the Aspergillus nidulans uric acid-xanthine/H(+) symporter UapA, which is a prototype member of the Nucleobase-Ascorbate Transporter (NAT) family. The model consists of 14 transmembrane segments (TMSs) divided into a core and a gate domain, the later being distinctly different from that of UraA. By implementing Molecular Mechanics (MM) simulations and quantitative structure-activity relationship (SAR) approaches, we propose a model for the xanthine-UapA complex where the substrate binding site is formed by the polar side chains of residues E356 (TMS8) and Q408 (TMS10) and the backbones of A407 (TMS10) and F155 (TMS3). In addition, our model shows several polar interactions between TMS1-TMS10, TMS1-TMS3, TMS8-TMS10, which seem critical for UapA transport activity. Using extensive docking calculations we identify a cytoplasm-facing substrate trajectory (D360, A363, G411, T416, R417, V463 and A469) connecting the proposed substrate binding site with the cytoplasm, as well as, a possible outward-facing gate leading towards the substrate major binding site. Most importantly, re-evaluation of the plethora of available and analysis of a number of herein constructed UapA mutations strongly supports the UapA structural model. Furthermore, modeling and docking approaches with mammalian NAT homologues provided a molecular rationale on how specificity in this family of carriers might be determined, and further support the importance of selectivity gates acting independently from the major central substrate binding site.

The aim of this research was to test empirically Elkind’s (1967, 1970, 1978) Piagetian theoretical formulation for the developmental nature of adolescent egocentrism. The contribution of this study is threefold because it includes: 1) Pubertal development (with a distinction between status and timing), which has been systematically ignored by other investigators; 2) a broad age range (11-18 year-old adolescents); and 3) a variety of manifestations and dimensions of egocentrism. The association of the two main forms of adolescent egocentrism—the imaginary audience and the personal fable—with age, gender, pubertal development, and formal operational thought was investigated. Participants were 314 adolescents who completed the Physical Development Scale (Petersen, Crockett, Richards, & Boxer, 1988), a battery of cognitive tasks (Demetriou, Efklides, & Platsidou, 1993), the Imaginary Audience Scale (Elkind & Bowen, 1979), the New Imaginary Audience Scale (Lapsley, Fitzgerald, Rice, & Jackson, 1989), the Personal Fable Scale (Elkind, personal communication, August 10, 1993), and the New Personal Fable Scale (Lapsley et al., 1989). Findings provided partial support for Elkind’s hypothesis. Only the imaginary audience in the form of self-consciousness was associated with grade. Systematic gender differences emerged for several dimensions of imaginary audience and personal fable. For only a few dimensions of imaginary audience and personal fable the expected associations with pubertal and cognitive development, as well as interesting interaction effects, were found. Results are discussed in terms of their implications for Elkind’s theory and for alternative interpretations of imaginary audience and personal fable.

The publication of the International Medical Informatics Association revised version of the existing international recommendations in health informatics / medical informatics education was welcome positively by the educational community. The recommendations help to establish courses and complete programs in the field of Biomedical and Health Informatics (BMHI), to further develop existing educational activities in the various nations and to support international initiatives. The paper focuses on the Master's courses, which are the most widely established programs following the recommendations. The number of citations of the recommendations shows the worldwide acceptance. However, an in-depth review is recommended.

The ASCT2 transport system catalyses a sodium-dependent antiport of glutamine and other neutral amino acids which is involved in amino acid metabolism. A library of 1,2,3-dithiazoles was designed, synthesized and evaluated as inhibitors of the glutamine/amino acid ASCT2 transporter in the model system of proteoliposomes reconstituted with the rat liver transporter. Fifteen of the tested compounds at concentration of 20 μM or below, inhibited more than 50% the glutamine/glutamine antiport catalysed by the reconstituted transporter. These good inhibitors bear a phenyl ring with electron withdrawing substituents. The inhibition was reversed by 1,4-dithioerythritol indicating that the effect was likely owed to the formation of mixed sulfides with the protein's Cys residue(s). A dose–response analysis of the most active compounds gave IC50 values in the range of 3–30 μM. Kinetic inhibition studies indicated a non-competitive inhibition, presumably because of a potential covalent interaction of the dithiazoles with cysteine thiol groups that are not located at the substrate binding site. Indeed, computational studies using a homology structural model of ASCT2 transporter, suggested as possible binding targets, Cys-207 or Cys-210, that belong to the CXXC motif of the protein.

This study evaluated the incidence of colonization and infection related to Central Vascular Catheters (CVC) in a tertiary care Greek hospital, as well as risk factors associated with catheter-related bloodstream infection (CRBSI). A total of 340 CVCs, were studied in relation to patient clinical and epidemiological data, CVC characteristics, and microbiological culture results. Risk factors were assessed. Pulsed field gel electrophoresis was used for the investigation of the clonal relationship of the isolates. The incidence for CRBSI and catheter colonization (CC) was 11.47 and 19.49 per 1,000 catheter days, respectively. Risk factors independently associated with CRBSI were use of corticosteroids, diabetes mellitus, solid organ neoplasm, long duration of catheterization, and changing the CVC dressing at intervals of 48 hours or more. Risk factors for CC were diabetes mellitus, hospitalization in ICU, and prolonged hospitalization. The predominant microorganisms isolated from CRBSI episodes were coagulase-negative staphylococci. All patients with CVC require constant infection surveillance and appropriate care by trained medical staff. Use of CVC for the shortest time possible, good hand hygiene and change of CVC dressing at intervals of less than 48 hours are infection prevention practices that need to be followed.

Schnitzler syndrome is a rare plasma cell disorder the pathogenesis of which is still not fully understood. We evaluated the circulating levels of four major angiogenic cytokines (VEGF, angiogenin, angiopoietin-1 and angiopoietin-2) and six bone remodeling markers (sRANKL, osteoprotegerin, dickkopf-1, CTX, osteocalcin and bone-specific alkaline phosphatase-bALP) in 13 patients with Schnitzler syndrome. At diagnosis, patients had elevated angiogenic cytokines. The mean VEGF levels were almost 3.5-fold higher in Schnitzler syndrome compared to controls, while 10 of 13 patients had higher VEGF than the upper control value. Successful treatment led to a significant reduction in VEGF. Patients with Schnitzler syndrome had increased bone formation (high bALP, osteocalcin and osteoprotegerin) which was not balanced by an increase in bone resorption (normal CTX and sRANKL). These data support a role for VEGF as a new minor criterion in the diagnosis and follow up of Schnitzler syndrome, while the uncoupling of bone remodeling in favor of bone formation justifies the presence of bone densification. ©2012 Ferrata Storti Foundation.

Multiple myeloma (MM) comprises 1% of all malignancies and 13% of hematological malignancies in the Caucasian population. Yearly incidence is 4/100,000 in the US and is higher in blacks and males [1]. The pathogenesis of the disease is relatively unknown; several chromosomal abnormalities have been related to the development of the disease, but none is characteristic of MM. Cyclin-D1 is a protein encoded by the CCND1 (bcl-1) gene on chromosome 11q13, and is an important regulator of G1 to S phase progression.

Indirubin derivatives gained interest in recent years for their anticancer and antimetastatic properties. The objective of the present study was to evaluate and compare the anticancer properties of the two novel bromo-substituted derivatives 6-bromoindirubin-3’-oxime (6BIO) and 7-bromoindirubin-3’-oxime (7BIO) in five different breast cancer cell lines. Cell viability assays identified that 6BIO and 7BIO are most effective in preventing the proliferation of the MDA-MB-231-TXSA breast cancer cell line from a total of five breast cancer cell lined examined. In addition it was found that the two compounds induce apoptosis via different mechanisms. 6BIO induces caspase-dependent programmed cell death through the intrinsic (mitochondrial) caspase-9 pathway. 7BIO up-regulates p21 and promotes G2/M cell cycle arrest which is subsequently followed by the activation of two different apoptotic pathways: (a) a pathway that involves the upregulation of DR4/DR5 and activation of caspase-8 and (b) a caspase independent pathway. In conclusion, this study provides important insights regarding the molecular pathways leading to cell cycle arrest and apoptosis by two indirubin derivatives that can find clinical applications in targeted cancer therapeutics. © 2012 Elsevier Inc.

Inflammatory masses or cysts occurring in the pelvis, thigh, and gluteal regions, often mimicking infection, occasionally arise after total hip arthroplasty procedures. Inflammatory pseudotumors comprise a subgroup of these lesions. Pseudotumors have been associated with pain, rashes, instability, neuropathy, and premature loosening of prosthetic components, often leading to early and difficult revision surgery. The association between such pseudotumors and metal-on-metal bearings has led to questions regarding the performance of these bearings in hip arthroplasty. We present a case of pseudotumor requiring revision surgery, which occurred uniquely around a metal-on-highly cross-linked polyethylene bearing.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

Context. EE Cep is an unusual long-period (5.6 yr) eclipsing binary discovered during the mid-twentieth century. It undergoes almost-grey eclipses that vary in terms of both depth and duration at different epochs. The system consists of a Be type star and a dark dusty disk around an invisible companion. EE Cep together with the widely studied ɛ Aur are the only two known cases of long-period eclipsing binaries with a dark, dusty disk component responsible for periodic obscurations. Aims: Two observational campaigns were carried out during the eclipses of EE Cep in 2003 and 2008/9 to verify whether the eclipsing body in the system is indeed a dark disk and to understand the observed changes in the depths and durations of the eclipses. Methods: Multicolour photometric data and spectroscopic observations performed at both low and high resolutions were collected with several dozen instruments located in Europe and North America. We numerically modelled the variations in brightness and colour during the eclipses. We tested models with different disk structure, taking into consideration the inhomogeneous surface brightness of the Be star. We considered the possibility of disk precession. Results: The complete set of observational data collected during the last three eclipses are made available to the astronomical community. The 2003 and 2008/9 eclipses of EE Cep were very shallow. The latter is the shallowest among all observed. The very high quality photometric data illustrate in detail the colour evolution during the eclipses for the first time. Two blue maxima in the colour indices were detected during these two eclipses, one before and one after the photometric minimum. The first (stronger) blue maximum is simultaneous with a "bump" that is very clear in all the UBV(RI)C light curves. A temporary increase in the I-band brightness at the orbital phase ~0.2 was observed after each of the last three eclipses. Variations in the spectral line profiles seem to be recurrent during each cycle. The Na i lines always show at least three absorption components during the eclipse minimum and strong absorption is superimposed on the Hα emission. Conclusions: These observations confirm that the eclipsing object in EE Cep system is indeed a dark, dusty disk around a low luminosity object. The primary appears to be a rapidly rotating Be star that is strongly darkened at the equator and brightened at the poles. Some of the conclusions of this work require verification in future studies: (i) a complex, possibly multi-ring structure of the disk in EE Cep; (ii) our explanation of the "bump" observed during the last two eclipses in terms of the different times of obscuration of the hot polar regions of the Be star by the disk; and (iii) our suggested period of the disk precession (~11-12 Porb) and predicted depth of about 2 m for the forthcoming eclipse in 2014. Appendix A is available in electronic form at http://www.aanda.orgTables B.1-B.36 are only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/544/A53

Background: The International Staging System (ISS) is the most widely used staging system for patients with multiple myeloma (MM). However, serum β2-microglobulin increases in renal impairment (RI) and there have been concerns that ISS-3 stage may include 'up-staged' MM patients in whom elevated β2-microglobulin reflects the degree of renal dysfunction rather than tumor load. Patients and methods: In order to assess the impact of RI on the prognostic value of ISS, we analyzed 1516 patients with symptomatic MM and the degree of RI was classified according to the Kidney Disease Outcomes Quality Initiative-Chronic Kidney Disease (CKD) criteria. Results: Forty-eight percent patients had stages 3-5 CKD while 29% of patients had ISS-1, 38% had ISS-2 and 33% ISS-3. The frequency and severity of RI were more common in ISS-3 patients. RI was associated with inferior survival in univariate but not in multivariate analysis. When analyzed separately, ISS-1 and ISS-2 patients with RI had inferior survival in univariate but not in multivariate analysis. In ISS-3 MM patients, RI had no prognostic impact either in univariate or multivariate analysis. Results were similar, when we analyzed only patients with Bence-Jones >200 mg/day. Conclusions: ISS remains unaffected by the degree of RI, even in patients with ISS-3, which includes most patients with renal dysfunction. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Background: Ankle sprain is an extremely common injury in soccer players. Despite extensive research, the intrinsic cause of this injury under noncontact conditions remains unclear. Purpose: To identify intrinsic risk factors for noncontact ankle sprains in professional soccer players. Study Design: Cohort study; Level of evidence, 2. Methods: One hundred professional soccer players were assessed in the preseason for potential risk factors of noncontact ankle. sprains. The assessment included (A) ankle joint asymmetries (right-left) in isokinetic muscle strength, flexibility, proprioception. and stability; (B) somatometric asymmetries; (C) previous injuries; and (D) lateral dominance traits. Noncontact ankle sprains were prospectively recorded and diagnosed for a full competition period (10 months). Results: Seventeen of the players sustained at least 1 noncontact ankle sprain. Logistic regression revealed that players with (A) eccentric isokinetic ankle flexion strength asymmetries (odds ratio [OR] = 8.88; 95% confidence interval [CI], 1.95-40.36, P = .005), (B) increased body mass index (OR = 8.16; 95% CI, 1.42-46.63, P = .018), and (C) increased body weight (OR = 5.72; 95% CI, 1.37-23.95, P = .017 ) each had a significantly higher risk of a noncontact ankle sprain. A trend for younger players(OR = 0.28; 95% CI, 0.061-1.24, P = .092) and for players with ankle laxity asymmetries (OR = 3.38; 95% CI, 0.82-14.00, P = .093) to be at greater risk for ankle sprain was also apparent to the limit of statistical significance (.05<P<.10). Conclusion: Functional strength asymmetries of the ankle flexors and increased body mass index and body weight raise the propensity for ankle sprains in professional soccer players. Age and asymmetries in ankle laxity are potential factors worth revisiting, as there was an indication for younger players and players with ankle instability to be at higher risk for ankle injury. Proper preseason evaluation may improve prevention strategies for this type of injury in soccer.

Intuition dictates that figurative language and especially metaphorical expressions should convey sentiment. It is the aim of this work to validate this intuition by showing that figurative language (metaphors) appearing in a sentence drive the polarity of that sentence. Towards this target, the current article proposes an approach for sentiment analysis of sentences where figurative language plays a dominant role. This approach applies Word Sense Disambiguation aiming to assign polarity to word senses rather than tokens. Sentence polarity is determined using the individual polarities for metaphorical senses as well as other contextual information. Experimental evaluation shows that the proposed method achieves high scores in comparison with other state-of-the-art approaches tested on the same corpora. Finally, experimental results provide supportive evidence that this method is also well suited for corpora consisting of literal and figurative language sentences.

We have studied the phase diagram of a Ba-1 xKxFe2As2 (T-c = 36.9 K) single crystal superconductor by employing ac-susceptibility measurements, both as a function of temperature for constant external magnetic field and of magnetic dc-field for constant temperature for angles Theta = (sic)(H, c-axis) = 0 degrees, 30 degrees, 45 degrees, 60 degrees, 75 degrees and 90 degrees, between the c-axis and the magnetic field. The irreversibility lines (H-irr(T, H)) are estimated from the onset of non-zero values of the amplitude of the third harmonic susceptibility. H-irr-lines for all the studied angles can be reproduced from the equation H-irr = H-0(Theta)(1 - T/T-c)(n), with n approximate to 4/3. From the angular dependence of H-0(Theta) parameter we estimated the anisotropy of the irreversibility lines. In the temperature interval [35, T-c] the anisotropy parameter was estimated gamma = H-irr(ab)/H-irr(c) = 2.2 +/- 0.1. The measurements of the real part of the fundamental (first harmonic) ac-susceptibility chi'(T) for constant temperature as a function of dc-magnetic field revealed, for high values of the ac-field amplitude, a second peak in the critical current. The second peak line is located far from H-irr-line and exists up to T-c. Although the particular sample has high critical densities, contrary to the predictions of the Bean's model, the maximum of the imaginary part of the fundamental ac-susceptibility chi '' exhibits lower values. This behavior could be explained by assuming a reversible motion of the flux lines around the pinning centers for low values of the ac-magnetic field amplitude. (C) 2012 Elsevier B. V. All rights reserved.

Tissue kallikrein (KLK1) and kallikrein-related peptidases (KLK2-15) comprise a family of 15 highly conserved secreted serine proteases with similar structural characteristics and a wide spectrum of functional properties. Both gene expression and protein activity of KLKs are rigorously controlled at various levels via diverse mechanisms, including extensive steroid hormone regulation, to exert their broad physiological role. Nevertheless, deregulated expression, secretion, and function of KLK family members has been observed in several pathological conditions and, particularly, in endocrine-related human malignancies, including those of the prostate, breast, and ovary. The cancer-related abnormal activity of KLKs upon substrates such as growth factors, cell adhesion molecules, cell surface receptors, and extracellular matrix proteins facilitate both tumorigenesis and disease progression to the advanced stages. The well-documented relationship between KLK status and the clinical outcome of cancer patients has led to their identification as promising diagnostic, prognostic, and treatment response monitoring biomarkers for these complex disease entities. The main objective of this review is to summarize the existing knowledge concerning the role of KLKs in prostate, breast, and ovarian cancers and to highlight their continually evolving biomarker capabilities that can provide significant benefits for the management of cancer patients.

This paper presents a systemic geopolitical and geostrategic analysis of the current enlarged region of the Middle East with respect to the Syrian effect, developing on the basis of the action of the Islamist movement and the re-distribution of power which it entails.

En este artículo se presenta la disponibilidad léxica como una herramienta práctica cuya investigación se puede explotar didácticamente en la enseñanza del léxico en LE.

Giant paraesophageal hernias (PEHs) are associated with progression of symptoms in up to 45 per cent of patients. Recently, many series have reported that laparoscopic repair of PEH is technically feasible, effective, and safe. A retrospective review of the University of Athens tertiary care hospitals patient database and the patient medical records identified 45 patients who underwent elective repair of a giant PEH between 2002 and 2009. Elective laparoscopic repair of a giant PEH was attempted in 45 patients who were treated with Gore-Tex dual mesh with or without Nissen fundoplication. They all had a mesh repair. Intraoperative complications included one pulmonary embolism and one recurrent hernia. The use of a mesh seems to be effective in the treatment of large hernias. It appears to offer the benefit of a shorter hospital stay and a quicker recovery.

We present estimates for late Holocene relative sea level change along the Tyrrhenian coast of Italy based on morphological characteristics of eight submerged Roman fish tanks (piscinae) constructed between the 1st century B.C. and the 2nd century A.D. Underwater geomorphological features and archaeological remains related to past sea level have been measured and corrected using recorded tidal values. We conclude that local sea level during the Roman period did not exceed 58 ± 5 cm below the present sea level. These results broadly agree with previous observations in the region but contrast with recent analysis that suggests a significantly larger sea level rise during the last 2000 years. Using a glacial isostatic adjustment model, we explain how regional sea level change departs from the eustatic component. Our calculation of relative sea level during the Roman period provides a reference for isolating the long-wavelength contribution to sea level change from secular sea level rise. Precise determination of sea level rise in the study area improves our understanding of secular, instrumentally observed, variations across the Mediterranean.

Lechaion’s ancient harbor is now a coastal swamp filled with sediments. Two natural factors explain the harbor’s abandonment: (1) tectonic uplift during historical times and (2) the location of the harbor basin in a serpentine depression protected from the sea. Although it undoubtedly functioned as a very efficient sediment trap, only modest sedimentation rates (<1 mm/yr) have been measured in the basin. This paradox suggests that the basin was dredged and that the extracted sediments were dumped, forming a number of mounds around the harbor edges. The transition from marine organics to silt is dated to 750–400 cal. B.C. and precedes the 1.2 m uplift of the harbor at around 340 B.C., which underscores the minimal impact of tectonic forcing factors. The presence of fine-grained sediments is consistent with an increasingly protected environment. The macrofauna indicate a low-energy environment enriched with organic matter and brackish conditions. All data suggest that this environment became isolated from the sea. Although a seismic uplift around 340 B.C. played a partial role in the evolution of the harbor, it is not the sole natural forcing agent involved in the silting up of the basin.

Three gravity cores collected from the NE Mediterranean (NEMR) across a transect from the northern Aegean Sea (North Skyros basin) to the south Cretan margin (SCM), were investigated for pollen and terrestrial biomarkers derived from epicuticular waxes of vascular plants during the last ~20 ky. Pollen data show diversified mixed temperate forest in the northern borderlands and enhanced Mediterranean vegetation in the southern areas, documenting an N-S climatic trend. Terrestrial plant biomarkers and their diagnostic geochemical indices exhibit latitudinal patterns which are interpreted in terms of the different delivery pathways (fluvial/runoff vs. atmospheric transport), resulting from the climate conditions during different periods. During the Late Glacial and early deglaciation periods (20-14 ka BP) relatively increased humidity (H-index) is recorded in the north Aegean Sea, while in the South drier climate was the limiting factor for vegetation development. During this interval, terrestrial n-alkanes showed increased accumulation rates, suggesting massive transport of terrestrial organic matter through runoffs and rivers, followed by weaker input after 14 ka BP. After ~11 ka BP a major expansion of forest cover is evidenced in the NEMR, accompanied by a higher H-index because of the climatic amelioration. The forest vegetation exhibited regionally different characteristics, with cool temperate taxa being more abundant in the Aegean cores, while the SCM record is being featured by Mediterranean elements. At the onset of the Holocene and throughout the Holocene Climatic Optimum the delivery of terrestrial biomarkers increased and became more significant in the Aegean sites compared to the SCM site. Within the Holocene, the average chain length (ACL) of long chain n-alkanes exhibits lower values in the northern Aegean than in the southeastern Aegean and SCM, indicating the predominance of warmer species southwards. Finally, the H-index records a conspicuous humidity increase between 5.4 and 4.3 ka BP in the south Aegean that coincides with an increase in the terrestrial biomarker supply and the deposition of a distinct sapropel-like layer, SMH (Sapropel Mid Holocene). Similar trends in T (temperature) and H indices are slightly delayed and attenuated in the northern Aegean and are accompanied by an increase in the ACL index. A noticeable increase in the accumulation rates (ARs) of terrestrial biomarkers and the HPA index values during this period are clearly recorded in all three cores, indicative of enhanced terrigenous inputs of organic matter along with higher in-situ preservation.

We have investigated electrical transport and photocurrent in single and multilayers of two-dimensional arrays of silicon nanocrystals (SiNCs) suitable for photovoltaic applications. The films were grown on quartz by low pressure chemical vapor deposition of Si and subsequent thermal oxidation steps. We found that at high voltages, electrical transport is governed by space charge limited currents due to the presence of traps. At low voltages, electrical transport is ohmic. Carrier mobility, carrier concentration, and trap density in the films were extracted from the electrical measurements. Combining photocurrent and absorption measurements for the films with different SiNC sizes, we found a remarkable similarity in the photon energy dependence of the photocurrent and of the absorbed light from the SiNCs, confirming a proportionality relation between the two quantities. Also, from the combined study of electrical transport and photocurrent, minority carrier lifetimes were extracted. © 2012 American Institute of Physics.

What's known on the subject? and What does the study add? L-dopa decarboxylase (DDC) has been documented as a novel co-activator of androgen receptor transcriptional activity. Recently, it was shown that DDC gene expression is significantly higher in patients with PCa than in those with BPH. In the present study, there was a significant association between the DDC gene expression levels and the pathological stage and Gleason score of patients with prostate cancer (PCa). Moreover, DDC expression was shown to be an unfavourable prognostic marker of biochemical recurrence and disease-free survival in patients with PCa treated by radical prostatectomy. OBJECTIVE: To determine whether L-dopa decarboxylase gene (DDC) expression levels in patients with prostate cancer (PCa) correlate to biochemical recurrence and disease prognosis after radical prostatectomy (RP). PATIENTS AND METHODS: The present study consisted of 56 samples with confirmed malignancy from patients with PCa who had undergone RP at a single tertiary academic centre. Total RNA was isolated from tissue specimens and a SYBR Green fluorescence-based quantitative real-time polymerase chain reaction methodology was developed for the determination of DDC mRNA expression levels of the tested tissues. Follow-up time ranged between 1.0 and 62.0 months (mean +/- SE, 28.6 +/- 2.1 month; median, 31.5 months). Time to biochemical recurrence was defined as the interval between the surgery and the measurement of two consecutive values of prostate-specific antigen (PSA) >/=0.2 ng/mL. RESULTS: DDC expression levels were found to be positively correlated with the tumour-node-metastasis stage (P = 0.021) and Gleason score (P = 0.036) of the patients with PCa. Patients with PCa with raised DDC expression levels run a significantly higher risk of biochemical recurrence after RP, as indicated by Cox proportional regression analysis (P = 0.021). Multivariate Cox proportional regression models revealed the preoperative PSA-, age- and digital rectal examination-independent prognostic value of DDC expression for the prediction of disease-free survival (DFS) among patients with PCa (P = 0.036). Kaplan-Meier survival analysis confirms the significantly shorter DFS after RP of PCa with higher DDC expression levels (P = 0.015). CONCLUSIONS: This is the first study indicating the potential of DDC expression as a novel prognostic biomarker in patients with PCa who have undergone RP. For further evaluation and clinical application of the findings of the present study, a direct analysis of mRNA and/or its protein expression level in preoperative biopsy, blood serum and urine should be conducted.

Two pivotal, phase III, randomised, placebocontrolled, registration trials (MM-009 and MM-010) showed that lenalidomide plus dexamethasone was more effective than placebo plus dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma. This pooled, retrospective subanalysis of MM-009 and MM-010 analysed outcomes according to patient age. A total of 704 patients (390 aged <65 years, 232 aged 65-74 years, and 82 aged ≥75 years) received lenalidomide or placebo, both in combination with dexamethasone. The overall response rate (ORR) was significantly higher in patients treated with lenalidomide plus dexamethasone versus placebo plus dexamethasone in all age groups (P<0.0001 for all). Median progression-free survival (PFS) and median time-to-progression (TTP) were similar, and both were significantly longer with lenalidomide plus dexamethasone in all age groups (P<0.001 for all). Median overall survival (OS) favoured lenalidomide plus dexamethasone in all age groups, although the difference was not statistically significant. Adverse events of anaemia, febrile neutropenia, deep-vein thrombosis, neuropathy, and gastrointestinal disorders increased with age. Lenalidomide combined with dexamethasone improved the ORR and prolonged PFS, TTP, and OS compared with placebo plus dexamethasone, irrespective of age. This finding was consistent with the overall MM-009 and MM-010 populations. © 2012 The Japanese Society of Hematology.

Objective: The aim of this study was to investigate maternal asymmetric dimethylarginine (ADMA) concentrations at the three trimesters of pregnancy in uncomplicated pregnancies and in women who developed preeclampsia or had small for gestational age infants (SGA) without preeclampsia. Methods: ADMA concentrations were retrospectively determined in the first, second and third trimester of pregnancy in 41 uncomplicated pregnancies, 10 pregnancies complicated with preeclampsia and 14 pregnancies that delivered a SGA baby. ADMA was measured with an ELISA kit. Results: Mean (±SD) concentrations of ADMA (μmol/L) in uncomplicated l pregnancies were: 0.51 ± 0.14; 0.52 ± 0.13; 0.58 ± 0.16 in the three trimesters, respectively. ADMA concentrations in SGA pregnancies were significantly lower in each trimester compared to uncomplicated pregnancies: (0.40 ± 0.10, p = 0.005 1st trim; 0.42 ± 0.10, p = 0.007 2nd trim; 0.45 ± 0.10, p = 0.007 3rd trim). Although pregnancies that developed preeclampsia had higher ADMA concentration in all trimesters compared to uncomplicated pregnancies (0.58 ± 0.10; 0.63 ± 0.14; 0.68 ± 0.11), the difference was statistically significant only in the 2nd trimester (p = 0.02). Conclusions: Maternal serum ADMA concentration tends to increase during normal pregnancy. Pregnancies with SGA infants had significantly lower ADMA levels in all trimesters of pregnancy. ADMA concentrations in the 2nd trimester was significantly elevated in pregnancies that later developed preeclampsia. © 2012 Informa UK, Ltd.

We present density-functional results on the lifetime of the (111) surface state of the noble metals. We consider scattering on the Fermi surface caused by impurity atoms belonging to the 3d and 4sp series. The results are analyzed with respect to film thickness and with respect to separation of scattering into bulk or into surface states. While for impurities in the surface layer the overall trends are similar to the long-known bulk-state scattering, for adatom-induced scattering we find a surprising behavior with respect to the adatom atomic number. A plateau emerges in the scattering rate of the 3d adatoms, instead of a peak characteristic of the d resonance. Additionally, the scattering rate of 4sp adatoms changes in a zigzag pattern, contrary to a smooth parabolic increase following Linde's rule that is observed in bulk. We interpret these results in terms of the weaker charge screening and of interference effects induced by the lowering of symmetry at the surface.

We report on the occurrence of strong nonlinear acousto-optic interactions in phoxonic structures, that support, simultaneously, acoustic and optical localized resonant modes, under the influence of acoustic losses. Deploying a detailed theoretical investigation of the acousto-optic coupling in the specific case of a one-dimensional phoxonic cavity, realized by homogeneous SiO2 and Si layers, we demonstrate the possibility for an enhanced modulation of light with sound through multi-phonon exchange mechanisms. A full electrodynamic and elastodynamic multiple scattering approach is employed to describe the optical and acoustic modes, and to account for their mutual interaction and the underlying effects both in time and frequency domains. In particular, we discuss the influence of hypersonic attenuation on the acousto-optic interaction by considering typical acoustic losses in the GHz regime.

BACKGROUND: Lobomycosis, also known as Jorge Lobo's disease, represents a rare chronic subcutaneous mycosis caused by the fungus Lacazia loboi, an organism that is found within lesions but has not been cultured to date. The natural reservoir of L. loboi is unknown but it is believed to be aquatic, or associated with soil and vegetation. More than 550 human cases have been reported, especially in patients with a history of travel or residence in endemic areas (Central and South America, particularly Brazil) or in communities along rivers. MAIN OBSERVATIONS: We describe a 64-year-old Greek female farmer living in a coastal region, who presented with an erythematous plaque on her left inner thigh resembling a keloid. The diagnosis was based on the triad: 1) absence of fungal growth in cultures, 2) positive direct microscopic examination of the lesion and 3) histopathology, all consistent with lobomycosis. Particularly, skin biopsy showed deep cutaneous fungal infection with granulomatous reaction. Fungal cells were found inside giant cells. The fungi were thick-walled with some budding, isolated or in short chains. Dermal fibrosis was present. Our patient had a medical history of common variable immunodeficiency but no history of travel to South or Central America. She probably acquired this rare infection by injury during her agricultural works. CONCLUSION: Our case represents probably the first documented case of human lobomycosis in Southeastern Europe. This case is unusual due to the rarity of lobomycosis in Mediterranean countries, particularly in Southeastern Europe.

In this longitudinal study, the craniofacial morphology and evaluated soft tissue profile changes, at 6 and 12 years of age in patients with complete bilateral cleft lip and palate (CBCLP) were compared. Lateral cephalograms from 148 patients with CBCLP, treated consecutively at three European cleft centers, Gothenburg (n (A) = 37), Nijmegen (n (B) = 26), and Oslo (n (C) = 85), were evaluated. Eighteen hard tissue and ten soft tissue landmarks were digitized. Paired t test, Pearson's correlation coefficients, and multiple regression models were applied for statistical analysis. ANOVA and Tukey-B, as a post hoc test, were used to evaluate the increments and compare centers. Hard and soft tissue data were superimposed using the generalized Procrustes analysis. For Nijmegen, the increments of the variables SNA, ANB, SN-NL, SN-ML, NL-ML, Snss, and Snpg were significantly different than the two other centers (p = 0.041 to <0.001). SNPg increments were significantly different between Nijmegen and Oslo (p = 0.002). The three cleft centers followed different treatment protocols, but the main differences in craniofacial morphology until 12 years of age were the growth pattern and the maxillary and upper incisor variables. Follow-up of these patients until facial growth has ceased, which may elucidate components for improving treatment outcome.

The 7th TNM classification clearly states that micrometastases detected by morphological techniques (HE stain and immunohistochemistry) should always be reported and calculated in the staging of the disease (pN1mi or M1), while patients in whom micrometastases are detected by non-morphological techniques (e.g., flow cytometry, reverse-transcriptase polymerase chain reaction) should still be classified as N0 or M0. In gastric cancer patients, micrometastases have been detected in lymph nodes, the peritoneal cavity and bone marrow. However, the clinical implications and/or their prognostic significance are still a matter of debate. Current literature suggests that lymph node micrometastases should be encountered for the loco-regional staging of the disease, while skip lymph node micrometastases should also be encountered in the total number of infiltrated lymph nodes. Peritoneal fluid cytology examination should be obligatorily performed in pT3 or pT4 tumors. A positive cytology classifies gastric cancer patients as stage IV. Although a curative resection is not precluded, these patients face an overall dismal prognosis. Whether patients with a positive cytology should be treated similarly to patients with macroscopic peritoneal recurrence should be evaluated further. Gastric cancer cells are detected with high incidence in the bone marrow. However, the published results make comparison of data between groups almost impossible due to severe methodological problems. If these methodological problems are overcome in the future, specific target therapies may be designed for specific groups of patients.

In the last 15 years, the genus Malassezia has been a topic of intense basic research on taxonomy, physiology, biochemistry, ecology, immunology, and metabolomics. Currently, the genus encompasses 14 species. The 1996 revision of the genus resulted in seven accepted taxa: M. furfur, M. pachydermatis, M. sympodialis, M. globosa, M. obtusa, M. restricta, and M. slooffiae. In the last decade, seven new taxa isolated from healthy and lesional human and animal skin have been accepted: M. dermatis, M. japonica, M. yamatoensis, M. nana, M. caprae, M. equina, and M. cuniculi. However, forthcoming multidisciplinary research is expected to show the etiopathological relationships between these new species and skin diseases. Hitherto, basic and clinical research has established etiological links between Malassezia yeasts, pityriasis versicolor, and sepsis of neonates and immunocompromised individuals. Their role in aggravating seborrheic dermatitis, dandruff, folliculitis, and onychomycosis, though often supported by histopathological evidence and favorable antifungal therapeutic outcomes, remains under investigation. A close association between skin and Malassezia IgE binding allergens in atopic eczema has been shown, while laboratory data support a role in psoriasis exacerbations. Finally, metabolomic research resulted in the proposal of a hypothesis on the contribution of Malassezia-synthesized aryl hydrocarbon receptor (AhR) ligands to basal cell carcinoma through UV radiation-induced carcinogenesis. © 2012, American Society for Microbiology. All Rights Reserved.

Background The aryl hydrocarbon receptor (AhR) is a nuclear receptor and transcriptional regulator with pleiotropic effects. The production of potent AhR ligands by Malassezia yeasts, such as indirubin, indolo[3,2-b]carbazole (ICZ), tryptanthrin and malassezin, has been associated with the pathogenesis of seborrhoeic dermatitis and pityriasis versicolor. Antigen-presenting cells in the skin can encounter microbes in the presence of these bioactive metabolites that could potentially modulate their function. Objectives To study the effects of the aforementioned naturally occurring ligands on AhR activation and Toll-like receptor (TLR)-induced maturation in human monocyte-derived dendritic cells (moDCs). Methods These indoles were screened for AhR activation capacity in moDCs employing CYP1A1 and CYP1B1 induction as read out and for their effects on the function of moDCs after TLR-ligand stimulation. Results Indirubin and ICZ were the most potent AhR ligands and were selected for subsequent experiments. Concurrent exposure of moDCs to indirubin or ICZ together with TLR agonists significantly augmented the AhR-mediated CYP1A1 and CYP1B1 gene expression. Additionally, mature DCs that were subsequently stimulated with AhR ligands showed increased AhR target gene expression. Moreover, these ligands limited TLR-induced phenotypic maturation (CD80, CD83, CD86, MHC II upregulation) of moDCs, reduced secretion of the inflammatory cytokines interleukin (IL)-6 and IL-12, and decreased their ability to induce alloreactive T-lymphocyte proliferation. Conclusions These results demonstrate that AhR agonists of yeast origin are able to inhibit moDC responses to TLR ligands and that moDCs can adapt through increased transcription of metabolizing enzymes such as CYP1A1 and CYP1B1. © 2012 British Association of Dermatologists.

Peripheral neuropathy (PN) is one of the most important complications of multiple myeloma (MM) treatment. PN can be caused by MM itself, either by the effects of the monoclonal protein or in the form of radiculopathy from direct compression, and particularly by certain therapies, including bortezomib, thalidomide, vinca alkaloids and cisplatin. Clinical evaluation has shown that up to 20% of MM patients have PN at diagnosis and as many as 75% may experience treatment-emergent PN during therapy. The incidence, symptoms, reversibility, predisposing factors and etiology of treatment-emergent PN vary among MM therapies, with PN incidence also affected by the dose, schedule and combinations of potentially neurotoxic agents. Effective management of treatment-emergent PN is critical to minimize the incidence and severity of this complication, while maintaining therapeutic efficacy. Herein, the state of knowledge regarding treatment-emergent PN in MM patients and current management practices are outlined, and recommendations regarding optimal strategies for PN management during MM treatment are provided. These strategies include early and regular monitoring with neurological evaluation, with dose modification and treatment discontinuation as indicated. Areas requiring further research include the development of MM-specific, patient-focused assessment tools, pharmacogenomic analysis of patient DNA, and trials to assess the efficacy of pharmacological interventions. © 2012 Macmillan Publishers Limited All rights reserved.

OBJECTIVE: To examine the association between a Mediterranean-style diet (MeDi) and brain magnetic resonance imaging white matter hyperintensity volume (WMHV). DESIGN: A cross-sectional analysis within a longitudinal population-based cohort study. A semiquantitative food frequency questionnaire was administered, and a score (range, 0-9) was calculated to reflect increasing similarity to the MeDi pattern. SETTING: The Northern Manhattan Study. PARTICIPANTS: A total of 1091 participants, of whom 966 had dietary information (mean age, 72 years; 59.3% women, 64.6% Hispanic, 15.6% white, and 17.5% black). MAIN OUTCOME MEASURES: The WMHV was measured by quantitative brain magnetic resonance imaging. Linear regression models were constructed to examine the association between the MeDi score and the log-transformed WMHV as a proportion of total cranial volume, controlling for sociodemographic and vascular risk factors. RESULTS: On the MeDi scale, 11.6% scored 0 to 2, 15.8% scored 3, 23.0% scored 4, 23.5% scored 5, and 26.1% scored 6 to 9. Each 1-point increase in MeDi score was associated with a lower log WMHV (β = -.04, P = .01). The only MeDi score component that was an independent predictor of WMHV was the ratio of monounsaturated to saturated fat (β = -.20, P = .001). CONCLUSIONS: A MeDi was associated with a lower WMHV burden, a marker of small vessel damage in the brain. However, white matter hyperintensities are etiologically heterogenous and can include neurodegeneration. Replication by other population-based studies is needed.

Objective:s To determine whether menopausal symptoms are associated with changes in arterial structure and function in healthy, recently postmenopausal women. Methods: One hundred and ten postmenopausal women aged 4555 years were included in the present cross-sectional study. Menopausal symptoms were recorded by the Greene Climacteric Scale. Anthropometric measures, blood pressure, serum lipids, glucose, insulin, sex and thyroid hormones were determined in each individual. Arterial structure, function and stiffness were assessed by intimamedia thickness (IMT), flow-mediated dilation and pulse-wave velocity, respectively. Results: Women with moderate to severe hot flushes had increased IMT compared to women with no or mild hot flushes (IMT in women with no hot flushes 0.61±0.08 mm, IMT in women with mild hot flushes 0.62±0.11 mm, IMT in women with moderate to severe hot flushes 0.67±0.11 mm; p = 0.034). This difference was independent of cardiovascular risk factors like age, menopausal age, smoking, blood pressure, adiposity, lipid levels, insulin resistance or hormone levels. No association was detected between psychological or psychosomatic symptoms and arterial indices. Furthermore, menopausal symptoms were not associated with serum sex steroids or thyroid hormone levels. Conclusions: Carotid IMT, a surrogate marker of subclinical atherosclerosis and cardiovascular risk, was found to be increased in women with vasomotor symptoms as compared to asymptomatic women. This association was independent of cardiovascular risk factors or endogenous hormone levels. It remains to be elucidated whether the presence of menopausal symptoms is an additional cardiovascular risk factor requiring preventive intervention. © 2012 International Menopause Society.

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine tumor of the skin. PRESENTATION OF CASE: We present a case of MCC in pelvic lymph nodes, revealed after surgical staging for endometrial cancer. A 54-year-old Caucasian woman presented to our department with a threemonth history of postmenopausal bleeding. After proper preoperative evaluation, the patient underwent total abdominal hysterectomy, bilateral salpingo-ophorectomy and pelvic lymph node dissection. The pathology report confirmed the presence of a small, grade I, endometrioid adenocarcinoma and MCC in the pelvic lymph nodes. Primary site of the disease could not been retrieved. The tumor board decided adjuvant chemotherapy (carboplatin and etoposide) and close follow-up every 2 months. Our patient is alive with no evidence of disease 12 months after surgery. DISCUSSION: It is noteworthy that 19% of the patients with MCC had lymph node metastasis with no apparent primary lesion. The mechanism of this regression remains unclear, although a higher apoptotic activity has been observed in MCC than other skin tumors. In addition, other co-malignancies have also been linked to MCC patients. The explanation for the frequent occurrence of other primary neoplasms in patients with MCC is still unclear. However, a reasonable cause could be an altered genetic profile or an immuno-compromised situation in these patients. CONCLUSION: Further analytic investigations are needed to clarify the role of various factors in the spontaneous regression or not of this neuroendocrine tumor as well as in the simultaneous genesis of other primary carcinomas. © 2012 Surgical Associates Ltd.

BACKGROUND: Metabolic syndrome (MetS) is defined as a clustering of metabolic disorders: abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. Although specific components of MetS have been associated with white matter hyperintensities (WMH), less is known about the association between MetS as a whole and WMH, especially in normal aging. We aimed to: (1) investigate this association in a cohort of healthy elderly individuals, and (2) examine the relationship between MetS and the regional distribution of WMH, to further understanding of the relationship between MetS and structural brain changes. METHODS: Analyses were carried out on 308 participants (48.1% men, age: 71.0 ± 3.9 years) from the French longitudinal ESPRIT (Enquête de Santé Psychologique--Risques, Incidence et Traitement) study, who were free of cerebrovascular disease cognitive and functional impairment. Logistic regression models were used to examine the cross-sectional association between MetS (defined using the National Cholesterol Education Program-Adult Treatment Panel III criteria) and (1) WMH volumes, and (2) WMH volumes according to their localization in insulofrontal and temporoparietal regions. RESULTS: After adjusting for potential confounders, participants with MetS had a twofold increased chance of presenting with high levels of WMH volume compared with those without (odds ratio [OR] = 2.74, 95% confidence interval [CI]: 1.25-6.03). MetS was specifically associated with an increase of temporoparietal WMH volumes, but no association was found between MetS and WMH localized in the insulofrontal region. CONCLUSION: Our findings suggest that effective management of MetS may reduce WMH accumulation in brain areas already vulnerable to the aging process.

The Mediterranean Basin and southern Europe are often affected by Saharan dust outbreaks, which influence the aerosol load and properties, air quality standards, visibility and human health. The present work examines, mainly of the meteorological point of view, three intense dust outbreaks occurred over Greece with duration of one or two days, on 4 and 6 February and 5-6 March 2009. The synoptic analysis on the dusty days showed the presence of low-pressure systems in the west coasts of Europe and the north Tyrrhenian Sea, respectively, associated with a trough reaching the north African coast. The result of these conditions was the strong surface and mid troposphere winds that carried significant amounts of dust over Greece. During the dusty days extensive cloud cover associated with the dust plume occurred over Greece. The air-mass trajectories showed a clear Saharan origin in all atmospheric levels, while the satellite (MODIS Terra/Aqua) observations as well as the model (DREAM) predictions verified the intense dust outbreaks over eastern Mediterranean and Greece. The ground based particulate matter concentrations in Athens were excessively increased on the dusty days (PM 150-560 g/m3), while significant dry and wet deposition occurred as forecasted by DREAM model. © 2012 P. T. Nastos.

Rhinoviruses (RVs) are the primary cause of upper respiratory tract infections, generally known as the common cold. Moreover, RV infections can trigger severe exacerbations of asthma and chronic obstructive pulmonary disease (COPD). We expressed the 4 major RV capsid proteins, VP1-VP4, in Escherichia coli and used these proteins as well as recombinant and synthetic VP1 fragments to study and map antibody responses in RV-infected humans. VP1, which on infection binds to ICAM 1, was identified as a major target for the memory immune response, residing in the IgG1 subclass and IgA class. Interestingly, this response was mainly directed against an N-terminal 20 mer peptide in VP1, P1a, which becomes exposed on intact RV only when it docks to its receptor ICAM 1. Molecular modeling using the 3-dimensional RV capsid structures revealed that P1a was localized inside the capsid and outside the areas involved in receptor binding or RV neutralization. Our results suggest misdirection of antibody responses against a nonprotective epitope as a mechanism how RV escapes immunity and causes recurrent infections. Based on these findings, it may be possible to design vaccines against RV infections and RV-induced respiratory diseases.

The aim of this work was to infer the phylogeny of the Greek endemic land-snail genus Codringtonia Kobelt 1898, estimate the time frame of the radiation of the genus, and propose a biogeographic scenario that could explain the contemporary distribution of Codringtonia lineages. The study took place in the districts of Peloponnese, Central Greece and Epirus of mainland Greece. Sequence data originating from three mtDNA genes (COI, COII, and 16S rDNA) were used to infer the phylogeny of the eight nominal Codringtonia species. Furthermore, the radiation time-frame of extant Codringtonia species was estimated using a relaxed molecular clock analysis and mtDNA substitution rates of land snails. The phylogenetic analysis supported the existence of six Codringtonia lineages in Greece and indicated that one nominal species (Codringtonia neocrassa) might belong to a separate genus distantly related to Codringtonia. The time frame of differentiation of Codringtonia species was placed in the Late Miocene-Pleistocene epoch. The dispersal-vicariance analysis performed indicated that most probably Codringtonia exhibited a north-to-south spread with the ancestral area being that of central Greek mainland, accompanied with duplication (speciation) and vicariance events. © 2011 Elsevier Inc.

Macroautophagy is a cellular catabolic process that involves the sequestration of cytoplasmic constituents into double-membrane vesicles known as autophagosomes, which subsequently fuse with lysosomes, where they deliver their cargo for degradation. The main physiological role of autophagy is to recycle intracellular components, under conditions of nutrient deprivation, so as to supply cells with vital materials and energy. Selective autophagy also takes place in nutrient-rich conditions to rid the cell of damaged organelles or protein aggregates that would otherwise compromise cell viability. Mitophagy is a selective type of autophagy, whereby damaged or superfluous mitochondria are eliminated to maintain proper mitochondrial numbers and quality control. While mitophagy shares key regulatory factors with the general macroautophagy pathway, it also involves distinct steps, specific for mitochondrial elimination. Recent findings indicate that parkin and the phosphatase and tensin homolog-induced putative kinase protein 1 (PINK1), which have been implicated in the pathogenesis of neurodegenerative diseases such as Parkinson's disease, also regulate mitophagy and function to maintain mitochondrial homeostasis. Here, we survey the molecular mechanisms that govern the process of mitophagy and discuss its involvement in the onset and progression of neurodegenerative diseases during aging.

The recent elucidation of crystal structures of a bacterial member of the NCS1 family, the Mhp1 benzyl-hydantoin permease from Microbacterium liquefaciens, allowed us to construct and validate a three-dimensional model of the Aspergillus nidulans purine-cytosine/H(+) FcyB symporter. The model consists of 12 transmembrane α-helical, segments (TMSs) and cytoplasmic N- and C-tails. A distinct core of 10 TMSs is made of two intertwined inverted repeats (TMS1-5 and TMS6-10) that are followed by two additional TMSs. TMS1, TMS3, TMS6, and TMS8 form an open cavity that is predicted to host the substrate binding site. Based on primary sequence alignment, three-dimensional topology, and substrate docking, we identified five residues as potentially essential for substrate binding in FcyB; Ser-85 (TMS1), Trp-159, Asn-163 (TMS3), Trp-259 (TMS6), and Asn-354 (TMS8). To validate the role of these and other putatively critical residues, we performed a systematic functional analysis of relevant mutants. We show that the proposed substrate binding residues, plus Asn-350, Asn-351, and Pro-353 are irreplaceable for FcyB function. Among these residues, Ser-85, Asn-163, Asn-350, Asn-351, and Asn-354 are critical for determining the substrate binding affinity and/or the specificity of FcyB. Our results suggest that Ser-85, Asn-163, and Asn-354 directly interact with substrates, Trp-159 and Trp-259 stabilize binding through π-π stacking interactions, and Pro-353 affects the local architecture of substrate binding site, whereas Asn-350 and Asn-351 probably affect substrate binding indirectly. Our work is the first systematic approach to address structure-function-specificity relationships in a eukaryotic member of NCS1 family by combining genetic and computational approaches.

The combination of docetaxel, cisplatin and fluorouracil is considered to be one of the reference regimens for advanced gastric cancer, but due to its major myelotoxicity, its use in clinical practice has become limited. This prospective phase II study evaluated the activity and toxicity of a modified regimen with lower doses of docetaxel and cisplatin combined with oral capecitabine instead of fluorouracil for patients with advanced gastric cancer. Treatment consisted of docetaxel at 60 mg/m(2) i.v. followed by cisplatin at 60 mg/m(2), both administered on day one, every three weeks. Capecitabine at 2 g/m(2) per day was administered in two divided doses for 14 days (days 2-15). Thirty six patients were enrolled in the study. The median age was 64 years and performance status (ECOG) was 0-1. All patients had advanced disease, 78% with liver metastases, 100% with intra-abdominal lymph node metastases and 67% with peritoneal implants. Out of the 36 patients, 13 had undergone gastric resection, 13 had received adjuvant chemotherapy with irinotecan-leucovorin-fluorouracil, while seven patients had undergone adjuvant radiotherapy. The remaining 23 patients presented with advanced inoperable disease. Among 36 evaluable for response cases, there were 16 (44.4%) (Confidence Internal (CI) 95%=28-60%), partial responses. Stable disease was recorded in 12 (33.3%), resulting in an overall disease control rate of 78% (CI 95%=69-87%), while 8 (22.3%) patients progressed on chemotherapy. The median response duration was 6 (range=3-8) months. The median time-to-progression was 5 (range=3-6) months and the median survival (after the administration of a second-line chemotherapy in 12 patients), was 12 (range=5-24) months. Myelotoxocity was the main toxicity, with grade 3-4 neutropenia occurring in 18 (50%) and febrile neutropenia in six (16%) patients. Granulocyte-Colony Stimulating Factor (G-CSF) support was given to 16 (44.4%) patients, while grade 3 thrombocytopenia was recorded in two (6%). In conclusion, this modified regimen of docetaxel-cisplatin-capecitabine appears to have comparable efficacy with that reported for the reference regimen, with acceptable toxicity when G-CSF support is provided. However, because due to the small size of the study, further investigation is warranted.

Banana fruit has become an important cause of fruit allergy in the recent years. Among the five registered IUIS allergens, Mus a 1 and Mus a 2 have been characterized in detail. In this study, molecular characterization and evaluation of the allergenic properties of β-1,3-glucanase from banana (Musa acuminata), denoted as Mus a 5, were performed.|The gene of Mus a 5 was cloned and sequenced. The obtained cDNA revealed a novel Mus a 5 isoform with an open reading frame encoding a protein of 340 amino acids comprising a putative signal peptide of 28 amino acid residues. By MALDI-TOF analysis Mus a 5 isolated from banana fruit revealed a molecular mass of 33451±67 Da. Two Mus a 5 isoforms (pI 7.7 and 8.0) were detected by 2D immunoblot with an identical N-terminal sequence. By mass fingerprint, 76 and 83% of the primary structure was confirmed for the two mature Mus a 5 isoforms, respectively. IgE reactivity to Mus a 5 was found in 74% of patients sensitized to banana fruit. Upregulation of basophil activation markers CD63 and CD203c was achieved with Mus a 5 in a concentration-dependent manner.|Mus a 5 is a functional allergen and a candidate for the component-resolved allergy diagnosis of banana allergy.

Wheat is an essential element in our nutrition but one of the most important food allergen sources. Wheat allergic patients often suffer from severe gastrointestinal and systemic allergic reactions after wheat ingestion. In this study, we report the molecular and immunological characterization of a new major wheat food allergen, Tri a 36. The cDNA coding for a C-terminal fragment of Tri a 36 was isolated by screening a wheat seed cDNA expression library with serum IgE from wheat food-allergic patients. Tri a 36 is a 369-aa protein with a hydrophobic 25-aa N-terminal leader peptide. According to sequence comparison it belongs to the low m.w. glutenin subunits, which can be found in a variety of cereals. The mature allergen contains an N-terminal domain, a repetitive domain that is rich in glutamine and proline residues, and three C-terminal domains with eight cysteine residues contributing to intra- and intermolecular disulfide bonds. Recombinant Tri a 36 was expressed in Escherichia coli and purified as soluble protein. It reacted with IgE Abs of ∼80% of wheat food-allergic patients, showed IgE cross-reactivity with related allergens in rye, barley, oat, spelt, and rice, and induced specific and dose-dependent basophil activation. Even after extensive in vitro gastric and duodenal digestion, Tri a 36 released distinct IgE-reactive fragments and was highly resistant against boiling. Thus, recombinant Tri a 36 is a major wheat food allergen that can be used for the molecular diagnosis of, and for the development of specific immunotherapy strategies against, wheat food allergy.

Genetics have undoubtedly become an integral part of biomedical science and clinical practice, with important implications in deciphering disease pathogenesis and progression, identifying diagnostic and prognostic markers, as well as designing better targeted treatments. The exponential growth of our understanding of different genetic concepts is paralleled by a growing list of genetic terminology that can easily intimidate the unfamiliar reader. Rendering genetics incomprehensible to the clinician however, defeats the very essence of genetic research: its utilization for combating disease and improving quality of life. Herein we attempt to correct this notion by presenting the basic genetic concepts along with their usefulness in the cardiology clinic. Bringing genetics closer to the clinician will enable its harmonious incorporation into clinical care, thus not only restoring our perception of its simple and elegant nature, but importantly ensuring the maximal benefit for our patients.

BACKGROUND: Mucinous tubular and spindle cell carcinoma (MTSC) is a rare and newly described type of renal cell carcinoma (RCC) with relatively indolent behavior. Although there are small series of this clinical entity in the literature, its histogenetic origin or line of differentiation remains unclear. PATIENTS AND METHODS: A 67-year-old woman was hospitalized for flank pain; imaging studies revealed a 6.5-cm mass in the right kidney. She was referred for fine needle aspiration of the lesion, which showed an epithelial tumor with round to oval nuclei associated with strands of metachromatic stromal tissue. Cytopathologic diagnosis was consistent with RCC. RESULTS: Subsequent right heminephrectomy was performed and the surgical pathology specimen showed an MTSC of the kidney. The patient has done well postoperatively, with 24 months of benign follow-up. CONCLUSION: A precise differential diagnosis between MTSC and other renal carcinomas (e.g. papillary RCC with sarcomatoid transformation) is important for predicting patient prognosis. Even though MTSC is a rare cause of renal masses, it should be included in the differential diagnosis, especially because its imaging might be misleading, mimicking other benign renal diseases. Heminephrectomy is the preferred treatment in these subjects.

Background: Multiple myeloma (MM) affects mainly elderly persons and because the population of octogenarians increases, it is common to treat patients ≥80 years of age. These patients are often not included in clinical trials; thus, there is limited data on their characteristics and treatment outcome. Patients and methods: We retrospectively analyzed 682 consecutive, unselected patients with newly diagnosed symptomatic myeloma who started treatment between January 1, 2003 and December 31, 2010. Results: We identified 155 (23%) patients ≥ 80 years of age. Compared to patients <80 years, octogenarians had poorer performance status (P < 0.001), anemia (P = 0.006), low serum albumin (P = 0.001), and advanced ISS (P < 0.001). The median survival of patients ≥80 years was 22 months, and 14% died within 2 months from therapy initiation. The median survival of patients ≥80 years who received upfront novel agents was 26 vs. 17 months for those who did not. ECOG performance status ≤1 and frontline use of novel agents were independently associated with better survival. Response to first-line therapy was associated with improved survival (29 vs. 16 months, P = 0.017). Conclusions: Patients ≥80 years of age present with features of advanced myeloma and impaired performance status. The addition of novel agents may improve their outcome, but careful assessment and prospective clinical trials targeting the population of elderly patients are needed. © 2012 John Wiley & Sons A/S.

PURPOSE: Although muscle mass and strength are thought to be closely related to throwing performance, there are few scientific data about these parameters in elite shot-putters. The purpose of this case report was to present longitudinal data for muscle strength and body composition in relation to performance of an elite male shot-putter. METHODS: A male national champion with the best rotational shot-put performance of 20.36 m (in 2010) was followed from 2003 to 2011 (current age: 29 y). Data regarding body composition (dual X-ray absorptiometry), as well as 1-repetition-maximum muscle strength (bench press, squat, snatch) and rotational shot-put performance, were collected every February for the last 9 y, 4 wk before the national indoor championship event. RESULTS: The athlete's personal-best performances in squat, bench press, and snatch were 175 kg, 210 kg, and 112.5 kg, respectively. His peak total lean body mass was 92.4 kg, bone mineral density 1.55 g/cm2, and lowest body fat 12.9%. His shot-put performance over these 9 years was significantly correlated with 1-repetition-maximum squat strength (r = .93, P < .01), bench press (r = .87, P < .01), and snatch (r = .92, P < .01). In contrast, shot-put performance was not significantly correlated with any of the body-composition parameters. CONCLUSIONS: The results of this case study suggest that elite rotational shot-put performance may not be directly correlated with lean body mass. Instead, it seems that it is closely related with measures of muscle strength.

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa protein of the lipocalin superfamily. This protein is expressed and secreted by immune cells, hepatocytes, and renal tubular cells in various pathologic states. NGAL has recently generated great interest as an early biomarker of renal injury. However, like many other endogenous biomarkers it is not produced by just one cell type and it exists in more than one molecular form. As recent research has shown different pathological conditions may involved in the production of this molecule. This review summarizes the current knowledge about the biology of NGAL and examines the role of this molecule of acute renal injury as well as in other pathologic conditions like neoplasia, anemia, pregnancy, cardiovascular disease chronic kidney disease and in cardiorenal syndrome. Commercial and research immunoassays are used to measure NGAL in both plasma and urine but these assays are not standardized. The existence of different molecular forms of NGAL and their expression at various disease states further complicates the interpretation of the results. Pre analytical issues and biological variation are also not fully elucidated. © 2012 by Walter de Gruyter. Berlin. Boston.

Purpose: To identify the criteria for hematologic and cardiac response to treatment in immunoglobulin light chain (AL) amyloidosis based on survival analysis of a large patient population. Patients and Methods: We gathered for analysis 816 patients with AL amyloidosis from seven referral centers in the European Union and the United States. A different cohort of 374 patients prospectively evaluated at the Pavia Amyloidosis Research and Treatment Center was used for validation. Data was available for all patients before and 3 and/or 6 months after initiation of first-line therapy. The prognostic relevance of different criteria for hematologic and cardiac response was assessed. Results: There was a strong correlation between the extent of reduction of amyloidogenic free light chains (FLCs) and improvement in survival. This allowed the identification of four levels of response: amyloid complete response (normal FLC ratio and negative serum and urine immunofixation), very good partial response (difference between involved and uninvolved FLCs [dFLC] < 40 mg/L), partial response (dFLC decrease > 50%), and no response. Cardiac involvement is the major determinant of survival, and changes in cardiac function after therapy can be reliably assessed using the cardiac biomarker N-terminal natriuretic peptide type B (NT-proBNP). Changes in FLC and NT-proBNP predicted survival as early as 3 months after treatment initiation. Conclusion: This study identifies and validates new criteria for response to first-line treatment in AL amyloidosis, based on their association with survival in large patient populations, and offers surrogate end points for clinical trials. © 2012 by American Society of Clinical Oncology.

Worldwide breast cancer (BC) constitutes a significant public health concern. Excess body weight is associated with postmenopausal BC (PBC) risk. Recent studies have shown that the constellation of obesity, insulin resistance and serum adipokine levels are associated with the risk and prognosis of PBC. Nicotinamide phosphoribosyl-transferase (Nampt), also known as visfatin and pre-B-cell-colony-enhancing factor, found in the visceral fat, represents a novel pleiotropic adipokine acting as a cytokine, a growth factor and an enzyme. It plays an important role in a variety of metabolic and stress responses as well as in the cellular energy metabolism, particularly NAD biosynthesis. Nampt exhibits proliferative, anti-apoptotic, pro-inflammatory and pro-angiogenic properties. Nampt's insulin-mimetic function remains a controversial issue. Circulating Nampt levels are increased in obese women. Also, Nampt levels are significantly elevated in women suffering from PBC than in healthy controls independently from known risk factors of BC, anthropometric and metabolic parameters as well as serum concentrations of well known adipokines. High expression of Nampt in BC tissues was reported to be associated with more malignant cancer behavior as well as adverse prognosis. Taking into account the mitogenicity of Nampt as well as its proliferative, anti-apoptotic and pro-angiogenic properties, a novel hypothesis is proposed whereas Nampt may be involved in the etiopathogenesis of PBC and may represent a missing link between overweight/obesity and PBC. Nampt could exert its effects on the normal and neoplastic mammary tissue by endocrine and paracrine mechanisms; Nampt could also be secreted by tumor epithelial cells in an autocrine manner. It could stimulate mammary epithelial cell proliferation, invasion, metastasis, and angiogenesis, which is essential for BC development and progression. Serum Nampt might be a novel risk factor as well as a potential diagnostic and prognostic biomarker in PBC. In addition, pharmacologic agents that neutralize biochemically Nampt or medications that decrease Nampt levels or downregulate signaling pathways downstream of Nampt may prove to be useful anti-cancer agents. The potential harmful effect on PBC risk due to vitamin B3 (nicotinic acid, a natural NAD precursor in the biosynthetic route leading to NAD) intake is speculated for the first time. In this hypothesis, the role of Nampt in BC carcinogenesis and progression is explored as well as the pathophysiological mechanisms that underlie the association between Nampt and PBC in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against PBC.

STAT3 and Akt signaling have been validated as potential molecular targets for treatment of cancers including melanoma. These small molecule inhibitors of STAT3 or Akt signaling are promising for developing anti-melanoma therapeutic agents. MLS-2438, a novel 7-bromoindirubin, a derivative of the natural product indirubin, was synthesized with a bromo-group at the 7-position on one indole ring and a hydrophilic group at the 3’-position on the other indole ring. We tested the anticancer activity of MLS-2438 and investigated its mechanism of action in human melanoma cell lines. Here, we show that MLS-2438 inhibits viability and induces apoptosis of human melanoma cells associated with inhibition of STAT3 and Akt signaling. Several pro-apoptotic Bcl-2 family proteins are involved in the MLS-2438 mediated apoptosis. MLS-2438 inhibits Src kinase activity in vitro and phosphorylation of JAK2, Src, STAT3 and Akt in cultured cancer cells. In contrast to the decreased phosphorylation levels of JAK2, Src, STAT3 and Akt, phosphorylation levels of the MAP K (Erk1/2) signaling protein were not reduced in cells treated with MLS-2438. These results demonstrate that MLS-2438, a novel natural product derivative, is a Src inhibitor and potentially regulates kinase activity of JAK2 and Akt in cancer cells. Importantly, MLS-2438 suppressed tumor growth with low toxicity in a mouse xenograft model of human melanoma. Our findings support further development of MLS-2438 as a potential small-molecule therapeutic agent that targets both STAT3 and Akt signaling in human melanoma cells. © 2012 Landes Bioscience.

Renal impairment is a major complication of multiple myeloma. Patients presenting with severe renal impairment represent a greater therapeutic challenge and generally have poorer outcome. However, once patients with renal impairment achieve remission, their outcomes are comparable with those of patients without renal impairment. Therapies that offer substantial activity in this setting are needed. Bortezomib, thalidomide, and lenalidomide have substantially improved the survival of patients with multiple myeloma. Here we review the pharmacokinetics, activity, and safety of these agents in patients with renal impairment. Bortezomib can be administered at the full approved dose and schedule in renally impaired patients; similarly, no dose reductions are required with thalidomide. The pharmacokinetics of lenalidomide is affected by its renal route of excretion, and dose adjustments are recommended for moderate/severe impairment. Substantial evidence has emerged showing that these novel agents improve outcomes of patients with renal impairment, including impairment reversal. Bortezomib, thalidomide, and lenalidomide (at the recommended doses) are active options for patients with mild to moderate impairment, although limited data are available for thalidomide. Information on lenalidomide-based combinations is still emerging, but the available data indicate considerable activity. Substantial evidence indicates that bortezomib-high-dose dexamethasone with or without a third drug (e.g., cyclophosphamide, thalidomide, or doxorubicin) is an appropriate option for patients with any degree of renal impairment. ©2012 AACR.

OBJECTIVE: The widely reported associations between various nutrients and cognition may occur through many biologic pathways including those of β-amyloid (Aβ). However, little is known about the possible associations of dietary factors with plasma Aβ40 or Aβ42. The aim of the current study was to evaluate the association between nutrient intake and plasma Aβ levels. METHODS: In this cross-sectional study, plasma Aβ40 and Aβ42 and dietary data were obtained from 1,219 cognitively healthy elderly (age >65 years), who were participants in a community-based multiethnic cohort. Information on dietary intake was obtained 1.2 years, on average, before Aβ assay. The associations of plasma Aβ40 and Aβ42 levels and dietary intake of 10 nutrients were examined using linear regression models, adjusted for age, gender, ethnicity, education, caloric intake, apolipoprotein E genotype, and recruitment wave. Nutrients examined included saturated fatty acid, monounsaturated fatty acid, ω-3 polyunsaturated fatty acid (PUFA), ω-6 PUFA, vitamin E, vitamin C, β-carotene, vitamin B(12), folate, and vitamin D. RESULTS: In unadjusted models that simultaneously included all nutrients, higher intake of ω-3 PUFA was associated with lower levels of Aβ40 (β = -24.7, p < 0.001) and lower levels of Aβ42 (β = -12.3, p < 0.001). In adjusted models, ω-3 PUFA remained a strong predictor of Aβ42 (β = -7.31, p = 0.02), whereas its association with Aβ40 was attenuated (β = -11.96, p = 0.06). Other nutrients were not associated with plasma Aβ levels. CONCLUSIONS: Our data suggest that higher dietary intake of ω-3 PUFA is associated with lower plasma levels of Aβ42, a profile linked with reduced risk of incident AD and slower cognitive decline in our cohort.

Members of the family Amphisteginidae have been nearly ubiquitous contributors to shelf carbonate facies through most of the Cenozoic. The most prolific carbonate producer of modern representatives is Amphistegina lobifera Larsen, which is the largest and shallowest dwelling of the Indo- Pacific taxa. This epiphytic, symbiont-bearing foraminifer is also a remarkably successful invasive species in coastal ecosystems of the eastern Mediterranean, where its shell production is altering the composition of shoreline sediment. This paper reports a temporal study of an A. lobifera population collected monthly between June 2008–May 2009 in the Vravron/Attica coastal ecosystem of the south Evoikos Gulf (Aegean Sea), where winter temperatures can drop below previously reported minima for the species. Monthly variations in size, frequency distribution, and abundance indicate that this population reproduced primarily during the summer (July–September), when both asexual and sexual reproduction occurred simultaneously, suggesting a predominantly coeval, one-year life span for each generation. However, a modest increase in juveniles in January indicates some winter reproduction. Comparison of these findings with previous studies shows that a) tolerance of low winter temperatures, b) adaptation of the life cycle to strong seasonality, and c) the mixotrophic feeding strategy have allowed A. lobifera to proliferate in the exceptionally clear, low nutrient, coastal waters of the Mediterranean Sea. These attributes elucidate how previous Cenozoic populations of Amphistegina were able to rapidly expand their latitudinal ranges and invade shallow epeiric seas during episodes of climatic warming. 

The present study revisited the problem of estimating Olympic success by critical demo-economic indicators. The sample consisted of the 75 winner countries at the Athens 2004 Olympic Games (not previously analyzed). Medal totals were log-linearly regressed on land, population, GDP, urban population, inflation, growth rate, unemployment, labor force, health expenditures, ex-host, and team size. Multiple regression assumptions were tested with proper diagnostics including collinearity. Olympic team size was the best single predictors of Olympic medals (R2 = 0.690, p < 0.001), and as an alternative criterion variable was significantly regressed on population, growth rate, health expenditure, and unemployment (R2 = 0.563, p < 0.001). Medal totals were significantly regressed on population, ex-host, health expenditure, growth rate, and unemployment (R2 = 0.541, p < 0.001). The classical population-GDP model extracted only 28% of the variance in total medals (R2 = 0.277, p < 0.001), and this was slightly improved when combined with unemployment (R2 = 0.365, p < 0.001). It appears that the size of the Olympic team plays the role of transmitting the composite impact of a country's size and economy to the end-phase of Olympic success. Winning Olympic medals depends on the combined potential of population, wealth, growth rate, unemployment, ex-host, and social-sport expenditures. Larger and wealthier countries win more medals by “producing” larger Olympic teams as a result of possessing more athletic talents and better support for social and sport related activities.

This paper examines long and short-run relationships among three emerging Balkan stock markets (Romania, Bulgaria and Croatia), two developed European stock markets (Germany and Greece) and United States (U.S.), during the period 2000 - 2005. We apply Johansen's (1988) cointegration methodology to test the long-run relationships between these markets and Granger's (1969) causality methodology in order to capture short-runcointegration. Our findings are mixed. We provide evidence on long-run relationships between the Bulgarian and Croatian stock markets and the developed markets. On the other hand, there is no any cointegration among the developed markets and the Romanian market. Moreover, there is no cointegrating relationship among the threeregional emerging markets, while short-run relationships exist only among the region. These results have crucial implications for investors regarding the benefits of international portfolio diversification.

We report on the eigenmodes of photonic crystals consisting of submicron homogeneous chiral spheres in a nonchiral isotropic medium, by means of full electrodynamic calculations using the layer-multiple-scattering method. It is shown that resonant modes of the individual spheres give rise to narrow bands that hybridize with the extended bands of the appropriate symmetry associated with light propagation in an underlying effective chiral medium. The resulting photonic dispersion diagram exhibits remarkable features, such as strong band bending away from the Bragg points with consequent negative-slope dispersion inside the first Brillouin zone and sizable frequency gaps specific to each polarization mode. We present a rigorous group-theory analysis to explain features of the calculated photonic band structure, peculiar to a system which possesses time-reversal but not space-inversion symmetry, and discuss some interesting aspects of the underlying physics.

By using highly sensitive millikelvin superconducting quantum interference device magnetometry, the magnitude of the Curie temperature as a function of the Mn concentration x is determined for thoroughly characterized Ga1−xMnxN. The interpretation of the results in the frame of tight-binding theory and of Monte Carlo simulations allows us to assign the spin interaction to ferromagnetic superexchange and to point out the limited accuracy of state-of-the-art ab initio methods in predicting the magnetic characteristics of dilute magnetic insulators.

Research suggests a link between parental divorce and negative child outcomes; however, the presence of parental depression may confound this relationship. Studies exploring the simultaneous effects of depression and parents' divorce on the adjustment of their children are scarce and rarely have a longitudinal design. This is the first three-generation study of the relative effects of depression and divorce on offspring psychopathology, based on data from a 25-year longitudinal study with families at high and low risk for depression. One hundred seventy-eight grandchildren (mean age = 13.9 years) of depressed and nondepressed parents and grandparents were evaluated by raters blind to their parents' and grandparents' clinical status. We found that in both low and high-risk children, divorce had a limited impact on child adjustment over and above familial risk for depression. Divorce had a significant effect on child outcomes only among high-risk grandchildren with a depressed grandparent and nondepressed parents, with this group showing a threefold risk for anxiety disorders. Results support previous findings suggesting that familial risk for depression largely overshadows the effect of parental divorce on child psychopathology. Possible reasons for the lack of association between divorce and child psychopathology among low-risk offspring are discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved) (journal abstract)

Pasteurella multocida is usually transmitted by animal contact; however, in a significant proportion of cases, no animal exposure can be identified. Although vertical transmission has been identified in neonates, horizontal human-to-human spread has not been documented. A case of neonatal sepsis and meningitis resulting from horizontal transmission of P. multocida is described.

OBJECTIVES: To evaluate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in managing pain arising from orthodontic interventions, such as archwire or separators placement. DATA SOURCES: Medline and Cochrane databases searched in February 2010 and updated in July 2010 using orthodontics and pain as the search terms. Additional studies located from Google Scholar, Clinical Trials and the reference lists of retrieved articles. STUDY SELECTION: Randomized controlled trials comparing NSAID to placebo using visual analogue scale (VAS) scores. DATA SYNTHESIS: Of the 1127 studies identified through database searches, seven were included for meta-analysis. Treatment effects (Hedges' g using random effects model) and 95% confidence intervals (CI) of the pain VAS scores were evaluated at 2, 6 and 24 h after intervention, during chewing and biting activities. Pain level at 2 h differed between the ibuprofen and placebo groups during biting (95% CI: -0.178 to -0.046), but not during chewing (95% CI: -0.551 to 0.148). At 6 h, the ibuprofen group exhibited lower pain levels during both activities (chewing 95% CI: -0.640 to -0.123, biting 95% CI: -0.857 to -0.172). At 24 h, no statistically significant difference could be detected between ibuprofen and placebo (chewing 95% CI: -0.642 to 0.112, biting 95% CI: -0.836 to 0.048). No statistically significant difference was found between ibuprofen and acetaminophen at any time point. CONCLUSION: Ibuprofen appears to lower orthodontic pain compared to placebo at 2 and 6 h after separators or archwire placement, but not at 24 h, when pain peaks.

In this phase 1/2 study, we explored the feasibility and activity of an oral regimen of lenalidomide with low-dose dexamethasone and low-dose oral cyclophosphamide (RdC) in patients with primary systemic light chain amyloidosis. RdC was given for up to 12 cycles in prespecified cohorts at escalated doses: 13 patients were treated in phase 1 and 24 in phase 2; 65% were previously untreated, and most had renal and/or cardiac involvement and elevated cardiac biomarkers. Lenalidomide 15 mg/d and cyclophosphamide 100 mg/d were further evaluated in phase 2. On intention to treat, 20 (55%) patients achieved a hematologic response, including 3 (8%) complete remissions. Hematologic responses were seen at all dose levels and in 4 of 5 patients who had received bortezomib previously. An organ response was recorded in 22% of patients on intention-to-treat and in 40% of patients who survived at least 6 months. The median time to progression was 10 months and the 2-year survival was 41%. Fatigue, nonneutropenic infections, and rash were the most common toxicities. The results of the present study show that RdC is an oral regimen with activity in primary systemic light chain amyloidosis and may be an additional treatment option, especially for patients with preserved organ function or for patients who cannot receive or who relapse after bortezomib. This study is registered at www.clinicaltrials.gov as NCT00981708. © 2012 by The American Society of Hematology.

A detailed analysis of the optical properties of photonic structures of metal-coated chiral spheres, calculated by the full electrodynamic layer-multiple-scattering method, is presented. Easily tunable narrow bands, originating from particle-like plasmon modes of the metallic shells, hybridize with the extended bands of the underlying effective chiral medium and give rise to sizable partial gaps and strong band bending with consequent negative-slope dispersion. The photonic band diagram is discussed in the light of group theory, in conjunction with relevant transmission spectra, and the occurrence of polarization-selective transmission and negative refraction for a short range of angles of incidence is demonstrated.

{OBJECTIVE: α-Klotho (α-KL), a protein with antiaging properties, regulates phosphate, calcium, and bone metabolism, induces resistance to oxidative stress, and may participate in insulin signaling. The role of α-KL in neonates, known to be prone to metabolic disturbances and oxidative stress, is not known. The aim of this study was to evaluate circulating soluble α-KL concentrations in preterm and full-term neonates and unravel possible correlations with growth, metabolism, and indices of oxidative stress. DESIGN: Prospective study. METHODS: Plasma-soluble α-KL levels were determined by specific ELISA in 50 healthy neonates (25 preterm, mean (s.d.) gestational age (GA) 33.7 (1.1) weeks, and 25 full-term infants) at days 14 and 28 of life. Associations of α-KL with anthropometric, metabolic parameters, and indices of oxidative stress were examined. RESULTS: α-KL levels were significantly higher in full-term than in preterm infants at both days 14 (1099 (480) pg/ml vs 884 (239) pg/ml respectively; P<0.05) and 28 (1277 (444) pg/ml vs 983 (264) pg/ml respectively; P<0.01). In both preterm and full-term infants, α-KL levels increased significantly from day 14 to 28 of life (P<0.001). Circulating α-KL concentrations correlated with GA (β=0.32

{Objective: To identify the websites most visited by patients regarding polycystic ovary syndrome (PCOS), and to evaluate the quality of information provided by these websites. Study design: We sought data regarding the popularity of sites providing information about PCOS regardless of the way the visitors reached the site. We then scrutinized the top sites for predefined quality check points to evaluate the quality of information provided, including Health on Net Foundation (HON) accreditation. Finally, we searched for the expansion of these sites in social networks (Facebook and Twitter). Results: Of the top 15 sites, 8 were HONcode certified. The mean performance of content presence for all sites was 7.33 (min = 4

To explore the impact of dose intensity (DI) in the adjuvant setting of breast cancer, a randomized phase III trial was conducted comparing postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide, methotrexate and fluorouracil (CMF)in high-risk breast cancer patients. From Oct 2000 to June 2005, 1,121 node-positive patients were randomized to dose-dense sequential epirubicin 110 mg/m 2 and paclitaxel (Taxol®, Bristol Myers-Squibb, Princeton, NJ) 250 mg/m 2 (group A), or concurrent epirubicin 83 mg/m 2 and paclitaxel 187 mg/m 2 (group B), both followed by three cycles of "intensified" combination chemotherapy with CMF. By protocol design total cumulative dose and duration of treatment were identical in both groups. Dose intensity of epirubicin and paclitaxel was double in the dose-dense arm. Prophylactic treatment with granulocyte colony-stimulating factor was given with the dose-dense treatments. Disease-free survival (DFS) was the primary endpoint. At a median follow-up of 76 months, 253 patients (23%) had documented disease relapse (123 vs. 130 in groups A and B, respectively) and 208 deaths (101, group A and 107, group B) had been observed. The 5-year DFS rate of 74 and 74% and OS rate of 86 and 85% were observed for group A and group B, respectively. No differences were found in DFS or OS between the two treatment groups (P = 0.78 and P = 0.45 for DFS and OS, respectively). Safety analysis results showing that both regimens were well tolerated and safe have been previously published (Fountzilas et al. Ann Oncol 2008). No DFS or OS benefit from the dose-dense sequential epirubicin and paclitaxel was detected when compared to the concurrent administration of the same drugs. No additional safety issues were raised with long-term follow-up. © 2011 Springer Science+Business Media, LLC.

This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis-conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including 'practicing allergists', general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA(2) LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries.

This study explores the pragmatic awareness of instructed L2 learners of Greek (economic migrants) by examining the extent to which these learners display differences in their recognition and rating of pragmatic and grammatical violations. Methodologically, the study is largely based on the Bardovi-Harlig & Dörnyei (1998) study on pragmatic awareness. However, unlike the former, it does not compare SL and FL learners, but two groups of SL learners with different length of residence in Greece. Hence, it attempts to reach conclusions with respect to the impact of residence on the development of pragmatic awareness. It is shown that both learner groups consistently recognise grammatical violations with greater frequency than pragmatic ones and rate the former as more severe than the latter. It is concluded that for this particular learner sample, length of residence alone is not a sufficient condition for the development of pragmatic awareness. The suggestion is made that this is due at least partly to the special circumstances of the participants, which do not allow for sufficient opportunities for social contact with native speakers. The conclusions have important implications both for the role of the L2 setting in pragmatic development and for language instruction.

This study investigates developmental patterns in the requestive behavior of foreign language learners of Greek. Drawing data from a DCT it attempts to explore the head acts and external/internal modification devices that learners of three different proficiency levels (lower intermediate, intermediate and advanced) employ when performing requests in one formal (+P, +D) and two informal (−P, −D) situations. The results suggest that although several aspects of the learners’ pragmatic competence develop with increasing proficiency, even the advanced learners’ performance lags far behind native speakers in several respects. Furthermore, it is shown that these learners’ behaviors lend considerable support to both the developmental stages of pragmatic competence acknowledged in the relevant literature (0125 and 0005) and to Bialystok's model regarding the acquisition of pragmatic competence. What is more, it lends a great deal of cross-linguistic validity to earlier finding regarding the development of requests in the interlanguage of FL learners.

Osteolytic bone disease is the most common complication of multiple myeloma, resulting in skeletalrelated events (SREs) that cause significant morbidity. Bone destruction in myeloma is due to an increased activity of osteoclasts coupled with suppressed bone formation by osteoblasts. Currently, bisphosphonates are the mainstay of the treatment of myeloma bone disease. Zoledronic acid and pamidronate have shown similar efficacy in reducing SREs in a randomized study in the conventional chemotherapy era. However, in a recent study (the Myeloma-IX trial of the UK Medical Research Council, MRC), zoledronic acid was found to be superior to clodronate in reducing SREs, but also it produced a survival advantage of approximately 10 months in patients with bone disease at baseline. During recent years, novel agents targeting bone have been used in myeloma. This review focuses on the established therapy of myeloma bone disease and also on recent advances in treatment that take advantage of the better understanding of the pathophysiology of bone disease. © Springer Science+Business Media, LLC 2012.

Aim: Ovarian carcinomas have been classified into types I and II according to the hypothesised mode of carcinogenesis and molecular characteristics. The prognostic significance of this classification has not been studied. Patients and methods: Five hundred and sixty-eight patients with histologically confirmed, ovarian, fallopian tube or peritoneal carcinomas, international federation of gynecology and obstetrics (FIGO) stages IIC-IV, treated with paclitaxel/platinum following cytoreductive surgery, were included in this analysis. Type I included low-grade serous, mucinous, endometrioid and clear-cell and type II high-grade serous, unspecified adenocarcinomas and undifferentiated carcinomas. Results: Median overall survival (OS) was 49 months for type I versus 45 for type II (p = 0.576). In contrast to type II, there was considerable prognostic heterogeneity among the subtypes included in type I. Cox regression analysis showed that cell-type classification: low-grade serous, mucinous, endometrioid, clear-cell, type II (high-grade serous, unspecified adenocarcinomas, undifferentiated carcinoma) was an independent predictor of survival (respective median OS 121 versus 15 versus 64 versus 29 versus 45 months, p = 0.003). On the contrary, histopathological subtype or tumour type (I versus II) did not offer additional prognostic information. Conclusion: The proposed model of ovarian tumourigenesis does not reflect tumour behaviour in advanced disease. Tumour-cell type is the most relevant histopathological prognostic factor in advanced ovarian cancer treated with platinum/paclitaxel. © 2012 Elsevier Ltd. All rights reserved.

The ideal bearing surface for young patients undergoing total hip replacement (THR) remains controversial. We report the five-year results of a randomised controlled trial comparing the clinical and radiological outcomes of 102 THRs in 91 patients who were < 65 years of age. These patients were randomised to receive a cobalt-chrome on ultra-high-molecular-weight polyethylene, cobalt-chrome on highly cross-linked polyethylene, or a ceramic-on-ceramic bearing. In all, 97 hip replacements in 87 patients were available for review at five years. Two hips had been revised, one for infection and one for peri-prosthetic fracture. At the final follow-up there were no significant differences between the groups for the mean Western Ontario and McMaster Universities osteoarthritis index (pain, p = 0.543; function, p = 0.10; stiffness, p = 0.99), Short Form-12 (physical component, p = 0.878; mental component, p = 0.818) or Harris hip scores (p = 0.22). Radiological outcomes revealed no significant wear in the ceramic group. Comparison of standard and highly cross-linked polyethylene, however, revealed an almost threefold difference in the mean annual linear wear rates (0.151 mm/year versus 0.059 mm/year, respectively) (p < 0.001).

In this work we propose an innovative estimation method for the minimum Doppler factor and energy content of the γ-ray emitting region of quasar 3C 279, using a standard proton synchrotron blazar model and the principles of automatic photon quenching. The latter becomes relevant for high enough magnetic fields and results in spontaneous annihilation of γ-rays. The absorbed energy is then redistributed into electron-positron pairs and soft radiation. We show that as quenching sets an upper value for the source rest-frame γ-ray luminosity, one has, by necessity, to resort to Doppler factors that lie above a certain value in order to explain the TeV observations. The existence of this lower limit for the Doppler factor also has implications on the energetics of the emitting region. In this aspect, the proposed method can be regarded as an extension of the widely used method for estimating the equipartition magnetic field using radio observations. In our case, the leptonic synchrotron component is replaced by the proton synchrotron emission and the radio by the very high energy γ-ray observations. We show specifically that one can model the TeV observations by using parameter values that minimize both the energy density and the jet power at the cost of high values of the Doppler factor. On the other hand, the modelling can also be done by using the minimum possible Doppler factor; this, however, leads to a particle-dominated region and high jet power for a wide range of magnetic field values. Despite the fact that we have focused on the case of 3C 279, our analysis can be of relevance to all TeV blazars favouring hadronic modelling that have, moreover, simultaneous X-ray observations.

In this work we propose an innovative estimation method for the minimum Doppler factor and energy content of the γ-ray emitting region of quasar 3C 279, using a standard proton synchrotron blazar model and the principles of automatic photon quenching. The latter becomes relevant for high enough magnetic fields and results in spontaneous annihilation of γ-rays. The absorbed energy is then redistributed into electron-positron pairs and soft radiation. We show that as quenching sets an upper value for the source rest-frame γ-ray luminosity, one has, by necessity, to resort to Doppler factors that lie above a certain value in order to explain the TeV observations. The existence of this lower limit for the Doppler factor also has implications on the energetics of the emitting region. In this aspect, the proposed method can be regarded as an extension of the widely used method for estimating the equipartition magnetic field using radio observations. In our case, the leptonic synchrotron component is replaced by the proton synchrotron emission and the radio by the very high energy γ-ray observations. We show specifically that one can model the TeV observations by using parameter values that minimize both the energy density and the jet power at the cost of high values of the Doppler factor. On the other hand, the modelling can also be done by using the minimum possible Doppler factor; this, however, leads to a particle-dominated region and high jet power for a wide range of magnetic field values. Despite the fact that we have focused on the case of 3C 279, our analysis can be of relevance to all TeV blazars favouring hadronic modelling that have, moreover, simultaneous X-ray observations.

Dual-modality contrast agents, such as radiolabeled nanoparticles, are promising candidates for a number of diagnostic applications, since they combine the advantages of two different imaging modalities, namely SPECT or PET imaging with MR imaging. The benefit of such a combination is to more accurately interpret disease and abnormalities in vivo, by exploiting the advantages of each imaging technique, i.e. high sensitivity for SPECT/PET, high resolution anatomical information for MRI. In this review article, we provide an overview of recent findings in the synthesis, evaluation and application of radiolabeled iron oxide nanoparticles as dual-modality SPECT/MRI and PET/MRI imaging probes.

Purpose: This study compared the efficacy and safety of patupilone with those of pegylated liposomal doxorubicin (PLD) in patients with platinum-refractory or -resistant epithelial ovarian, primary fallopian tube, or primary peritoneal cancer. Patients and Methods: Patients with three or fewer prior regimens were eligible if they had received first-line taxane/ platinum-based combination chemotherapy and were platinum refractory or resistant. Patients were randomly assigned to receive patupilone (10 mg/m 2 intravenously every 3 weeks) or PLD (50 mg/m2 intravenously every 4 weeks). Results: A total of 829 patients were randomly assigned (patupilone, n = 412; PLD, n = 417). There was no statistically significant difference in overall survival (OS), the primary end point, between the patupilone and PLD arms (P = .195; hazard ratio, 0.93; 95% CI, 0.79 to 1.09), with median OS rates of 13.2 and 12.7 months, respectively. Median progression-free survival was 3.7 months for both arms. The overall response rate (all partial responses) was higher in the patupilone arm than in the PLD arm (15.5% v 7.9%; odds ratio, 2.11; 95% CI, 1.36 to 3.29), although disease control rates were similar (59.5% v 56.3%, respectively). Frequently observed adverse events (AEs) of any grade included diarrhea (85.3%) and peripheral neuropathy (39.3%) in the patupilone arm and mucositis/stomatitis (43%) and hand-foot syndrome (41.8%) in the PLD arm. Conclusion: Patupilone did not demonstrate significant improvement in OS compared with the active control, PLD. No new or unexpected serious AEs were identified. © 2012 by American Society of Clinical Oncology.

The mammalian target of rapamycin (mTOR) plays a role in controlling malignant cellular growth. mTOR inhibitors, including rapamycin (sirolimus), are currently being evaluated in cancer trials. However, a significant number of tumors are rapamycin resistant. In this study, we report that the ability of rapamycin to downregulate Skp2, a subunit of the ubiquitin protein ligase complex, identifies tumors that are sensitive to rapamycin. RNA interference (RNAi)-mediated silencing of Skp2 in human tumor cells increased their sensitivity to rapamycin in vitro and inhibited the growth of tumor xenografts in vivo. Our findings suggest that Skp2 levels are a key determinant of antitumor responses to mTOR inhibitors, highlighting a potentially important pharmacogenomic marker to predict sensitivity to rapamycin as well as Skp2 silencing strategies for therapeutic purposes.

Endometriosis is a multifactorial disease with unclear pathogenesis. Urinary tract endometriosis occurs in about 1% of all endometriotic lesions while isolated ureteral endometriosis is extremely rare. We present a case of intrinsic ureteral endometriosis causing ureteral stenosis in a 40-year's old woman, in combination with intestinal, extensive peritoneal and ovarian endometriosis. The clinicopathological features and investigation methods used, as well as the treatment approach are discussed. An individual therapy plan depending mainly on the patient's age, desire for children and the extent of the endometriotic foci should always be attempted. Collaboration between gynecologists and urologists was essential in our cases.

Integrating a gender perspective means eliminating the wastage of talent— utilizing all human resources— and as a result boosting innovation, a prerequisite for economic growth and effective sustainable development. In the last decade studies confirm that companies, firms, organizations and institutions that recognise talent in any form and make good use of it show greater success rates with regard to profits and sustainability. Research shows that women are an economic force to be reckoned with for sustainable economic recovery. This does not mean that women are inherently more talented and better skilled than men. It does however indicate that companies that have utilized their entire talent pool and identified and promoted female talent into leadership roles, have a vital competitive advantage. Surveys also confirm that female-led ICT businesses and women-owned firms (women entrepreneurs) have been successfully competing in the global market, the latter using more high technology systems than their male counterparts. Despite gender mainstreaming policies, legislation and the recognition by many companies, organizations and institutions that diversity is essential, women are less satisfied with their careers as they still lag behind men in compensation and advancement. In examining the three major gender gaps— the leadership gap, the pay gap and the participation gap— this paper argues that integrating a gender perspective is vital in order to eliminate gender devaluation, namely the subtle processes by which women’s contributions are minimized, undervalued or devalued in the so-called male professions. Integrating a gender perspective, a social, cultural and technical process, requires shifts not only in organisational practices, attitudes or ways of thinking, but also in resource allocations, goals and structures along with monitoring processes. This paper argues for an Alternative Model which entails: recruitment and politicizing the personal, namely "flexibility re-thought" along with technology as an enabler, rethinking and redefining the model for professional life, auditing compensation practices, identifying high-potential people and re-training returners. Specifically, gender diversity mainstreaming (integrating a gender perspective) in science, technology, engineering and math (STEM), research and development (R&D), the academia, product and service innovation, health action and services, innovation management and economic global competition, which is becoming increasingly tough, means redefining professional success and concepts of excellence. It requires setting up an all encompassing European collaborative platform or hub of information that will encourage future debates and synergies for establishing measures and best practices at many levels, finding alternative paths to advancement and participation (eg. A holistic approach, flexible work, eliminating age barriers for men and women, rewarding social service), identifying the voice of the next generation, creating opportunities for visibility, testimonial sharing, generating insights on how to contribute effectively to organizational growth, formal mentoring programs for both women and men, ethnic minority groups, among other things.   Keywords: wastage-leakage of talent, gender devaluation, gender fatigue, tokenism, glass escalator, gender energy, renegotiating concepts of excellence/success ------------------------------------------------------------------------------------------------------------Kamberidou, Irene & Fabry, Eva (2012). The paper was presented at the INNOVACIONES CIENTÍFICAS Y PERSPECTIVA DE GÉNERO (Scientific Innovations and the Gender Perspective) on 12-13 April, Madrid Spain. Organised by CIREM Foundation: Centre for European Initiatives and Research in the Mediterranean (CIREM).   Click and read the article: http://gender-it.eu/wp-content/uploads/2012/03/S1_kamberidou-y-fabry.pdf Redefining Professional Success and Concepts of Excellence: Integrating a Gender Perspective « genderit

AIMS: Desmin, the muscle-specific intermediate filament protein, is a major target in dilated cardiomyopathy and heart failure in humans and mice. The hallmarks of desmin-deficient (des(-/-)) mice pathology include pronounced myocardial degeneration, extended fibrosis, and osteopontin (OPN) overexpression. We sought to identify the molecular and cellular events regulating adverse cardiac remodelling in des(-/-) mice and their potential link to OPN. METHODS AND RESULTS: In situ hybridization, histology, and immunostaining demonstrated that inflammatory cells and not cardiomyocytes were the source of OPN. RNA profile comparison revealed that activation of inflammatory pathways, sustained by innate immunity mechanisms, predominated among all changes occurring in degenerating des(-/-) myocardium. The expression of the most highly up-regulated genes (OPN: 226x, galectin-3: 26x, osteoactivin/Gpnmb/DC-HIL: 160x and metalloprotease-12: 98x) was associated with heart infiltrating macrophages. To evaluate the role of OPN, we generated des(-/-)OPN(-/-) mice and compared their cardiac function and remodelling indices with those of des(-/-). Osteopontin promoted cardiac dysfunction in this model since des(-/-)OPN(-/-) mice showed 53% improvement of left ventricular function, paralleled to an up to 44% reduction in fibrosis. The diminished fibrotic response in the absence of OPN could be partly mediated by a dramatic reduction in myocardial galectin-3 levels, associated with an impaired galectin-3 secretion by OPN-deficient infiltrating macrophages. CONCLUSION: Cardiomyocyte death due to desmin deficiency leads to inflammation and subsequent overexpression of a series of remodelling modulators. Among them, OPN seems to be a major regulator of des(-/-) adverse myocardial remodelling and it functions at least by potentiating galectin-3 up-regulation and secretion.

Replication protein A (RPA) is an ssDNA-binding protein required for the initiation of DNA replication and the stabilization of ssDNA. Collaboration with several molecules, that is, the MCM2-7 complex, has been suggested to be imperative for its multifaceted role. In this study, we investigated the immunohistochemical expression of the RPA2 subunit in correlation with the MCM-2 and MCM-5 and Ki67 index, and assessed its prognostic significance in 76 patients with nonearly ovarian adenocarcinomas, the majority of whom had a serous histotype. RPA2 protein expression was observed in all cases, whereas the staining intensity varied from weak to strong. RPA2 expression was correlated with the tumor stage in the entire cohort and in serous tumors (P=0.0053 in both relationships). Moreover, RPA2 immunoexpression was positively correlated with MCM-2 (P=0.0001) and MCM-5 (P<0.0001) expression, but was unrelated to the Ki67 index (P>0.10). In multivariate survival analysis, RPA2 expression emerged as an independent predictor of adverse outcome (P<0.0001) along with tumor histologic grade. RPA2 remained an independent predictor of survival (P=0.002) even after adjustment for MCM-2 and MCM-5 expression and when analysis was restricted to serous carcinomas (P=0.004). Our results further support the interrelation of RPA2 protein with MCM-2 and MCM-5 in OCs. Moreover, RPA2 protein may play an important role in ovarian tumorigenesis, and may serve as a useful independent molecular marker for stratifying patients with OC in terms of prognosis. © 2012 International Society of Gynecological Pathologists.

Recently Varvoglis and Hadjidemetriou (Astrophys. Space Sci. doi:10.1007/s10509-012-1060-3, 2012; hereafter referred to as paper VH) have raised two points concerning the model of the restricted three-body problem with variable mass presented in our paper (Zhang et al. in Astrophys. Space Sci. 337:107, 2012; hereafter referred to as paper ZZX) and made intensive investigations of this model. These points and investigations are very useful and here we provide some explanation and supplementary specification regarding the model presented in the paper ZZX.

In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.

In a retrospective pooled analysis of 11 clinical trials of lenalidomide-based therapy for relapsed/refractory multiple myeloma (MM; N = 3846), the overall incidence rate (IR, events per 100 patientyears) of second primary malignancies (SPMs) was 3.62. IR of invasive (hematologic and solid tumor) SPMs was 2.08, consistent with the background incidence of developing cancer. In a separate analysis of pooled data from pivotal phase 3 trials of relapsed or refractory MM (N = 703), the overall IR of SPMs was 3.98 (95% confidence interval [CI], 2.51- 6.31) with lenalidomide/dexamethasone and 1.38 (95% CI, 0.44-4.27) with placebo/ dexamethasone; IRs of nonmelanoma skin cancers were 2.40 (95% CI, 1.33-4.33) and 0.91 (95% CI, 0.23-3.66), respectively; IRs of invasive SPMs were 1.71 (95% CI, 0.86-3.43) and 0.91 (95% CI, 0.23-3.66), respectively. The risk of SPMs must be taken into account before initiating lenalidomide treatment. In the context of the observed survival benefit in relapsed or refractory MM patients, the benefit/risk profile of lenalidomide/dexamethasone remains positive. © 2012 by The American Society of Hematology.

Human rhinoviruses, major precipitants of asthma exacerbations, induce lower airway inflammation and mediate angiogenesis. The purpose of this study was to assess the possibility that rhinoviruses may also contribute to the fibrotic component of airway remodeling.|Levels of basic fibroblast growth factor (bFGF) mRNA and protein were measured following rhinovirus infection of bronchial epithelial cells. The profibrotic effect of epithelial products was assessed by DNA synthesis and matrix metalloproteinase activity assays. Moreover, epithelial cells were exposed to supernatants from cultured peripheral blood mononuclear cells, obtained from healthy donors or atopic asthmatic subjects and subsequently infected by rhinovirus and bFGF release was estimated. bFGF was also measured in respiratory secretions from atopic asthmatic patients before and during rhinovirus-induced asthma exacerbations.|Rhinovirus epithelial infection stimulated mRNA expression and release of bFGF, the latter being positively correlated with cell death under conditions promoting rhinovirus-induced cytotoxicity. Supernatants from infected cultures induced lung fibroblast proliferation, which was inhibited by anti-bFGF antibody, and demonstrated increased matrix metalloproteinase activity. Rhinovirus-mediated bFGF release was significantly higher in an in vitro simulation of atopic asthmatic environment and, importantly, during rhinovirus-associated asthma exacerbations.|Rhinovirus infection induces bFGF release by airway epithelium, and stimulates stroma cell proliferation contributing to airway remodeling in asthma. Repeated rhinovirus infections may promote asthma persistence, particularly in the context of atopy; prevention of such infections may influence the natural history of asthma.

More aggressive treatment approaches (methotrexate, cytarabine, cyclophosphamide, vincristine, prednisone, and bleomycin [the MACOP-B regimen] or consolidation with high-dose therapy and autologous stem cell transplantation) have been considered to be superior to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with primary mediastinal large B-cell lymphoma (PMLBCL). Rituximab-CHOP (R-CHOP) is the standard of care for diffuse large B-cell lymphoma, whereas efficacy in PMLBCL has not been adequately confirmed. Patient and Methods. Seventy-six consecutive PMLBCL patients who received R-CHOP with or without radiotherapy (RT) were compared with 45 consecutive historical controls treated with CHOP with or without RT. Baseline characteristics of the two groups were balanced. Results. The rate of early treatment failure was much lower with R-CHOP with or without RT (9% versus 30%; p =.004). The 5-year freedom from progression rate after R-CHOP with or without RT was 81%, versus 48% for CHOP with or without RT (p < .0001). The 5-year event-free survival rates were 80% and 47% (p < .0001) and the 5-year overall and lymphoma-specific survival rates were 89% and 69% (p = .003) and 91% and 69% (p = .001), respectively, with only seven of 76 lymphoma-related deaths. Among R-CHOP responders, 52 of 68 received RT. Conclusions. Based on these results, most patients with PMLBCL appear to be cured by R-CHOP in 21-day cycles with or without RT, which could be the current standard of care. Therefore, the need for more aggressive treatment strategies is questionable unless high-risk patients are adequately defined. Further studies are required to establish the precise role of RT. ©AlphaMed Press.

Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD) but also with various types of malignancies. Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties. Circulating adiponectin levels, which are determined predominantly by genetic factors, diet, physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express adiponectin receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of adiponectin. Studies in both animals and humans have investigated adiponectin and adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either adiponectin per se or medications that increase adiponectin levels or up-regulate signaling pathways downstream of adiponectin may prove to be useful anticancer agents. This review presents the role of adiponectin in carcinogenesis and cancer progression and examines the pathophysiological mechanisms that underlie the association between adiponectin and malignancy in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against obesity-associated malignancies.

The scope of the present study is to assess the influence of meteorology on different diameter particles (PM 10, PM 2.5, PM 2.5-10) during a 53months long experimental campaign at an urban Mediterranean area. Except for the investigation of the wind, temperature and relative humidity role, day by day synoptic conditions were classified over the Attica peninsula in order to explore as well, the role of the synoptic scale atmospheric circulation. The strong dependence of the aerosols character on their various sources, not only explain the different diameter particles behavior and their differentiation with the inorganic pollutants but also highlights the need for an effective emission policy. High PM 10 and PM 2.5-10 concentrations found to be closely related to the southwesterly regime, suggesting long range transport from the ’polluted’ south sector while the general prevalence of the secondary particles generation revealed the health hazard. PM 2.5 showed a weaker correlation than the bigger particles with both the circulation patterns and the parameters’ fluctuations. Temporal pollutants variations were clearly governed by the emissions patterns while the low wind speed was not necessarily a good indicator of high concentration levels. Finally it was found that only during the open/close anticyclonic days and the southwesterly wind regime the morning levels were continuously higher than those of the night. © 2012 Elsevier B.V.

We have performed the Fourier decomposition analysis of 8- and 13-yr V-band light curves of a carefully selected sample of 454 fundamental-mode RR Lyrae variables (RRab type), detected in an ≃14 square degree area of the Small Magellanic Cloud (SMC) and listed in the Optical Gravitational Lensing Experiment, phase III, Catalogue of Variable Stars. The Fourier decomposition parameters were used to derive metal abundances and distance moduli, following the methodology described by Kapakos, Hatzidimitriou & Soszyński. The average metal abundance of the RRab stars on the new scale of Carretta et al. was found to be <[Fe/H]C09> = -1.69 ± 0.41 dex (std, with a standard error of 0.02 dex). A tentative metallicity gradient of -0.013 ± 0.007 dex kpc-1 was detected, with increasing metal abundance towards the dynamical centre of the SMC, but selection effects are also discussed. The distance modulus of the SMC was re-estimated and was found to be <μ> = 19.13 ± 0.19 (std) in a distance scale where the distance modulus of the Large Magellanic Cloud (LMC) is μLMC = 18.52 ± 0.06 (std). The average 1σ line-of-sight depth was found to be σ int =5.3±0.4 kpc (std), while spatial variations of the depth were detected. The SMC was found to be deeper in the north-eastern region, while metal-richer and metal-poorer objects in the sample seem to belong to different dynamical structures. The former have smaller scale height and may constitute a thick disc, its width being 10.40 ± 0.02 kpc, and a bulge whose size (radius) is estimated to be 2.09 ± 0.81 kpc. The latter seem to belong to a halo structure with a maximum depth along the line of sight extending over 16 kpc in the SMC central region and falling to ∼12 kpc in the outer regions.

Oseltamivir was administered at 1.0 mg/kg b.i.d. to 13 neonates exposed to influenza H1N1. No influenza, neurologic, or laboratory adverse effects occurred. The mean Cmax values for oseltamivir and oseltamivir carboxylate were found to be lower than those reported for children 1 to 5 years old, whereas Tmax values were similar to children 1 to 5 years old. Age and gender were found to significantly affect oseltamivir clearance.

Introduction: Sclerostin is a cysteine-knot-containing protein, which is produced by osteocytes and inhibits osteoblast function. The aim of this review is to summarize the data about the role of sclerostin in cancer-induced bone disease. Areas covered: We performed a thorough search for articles in the PubMed using the words "sclerostin, cancer, multiple myeloma", and for similar abstracts that were presented in the ASH and ASCO annual meetings (2005 2011). In multiple myeloma, sclerostin is produced by myeloma cells and elevated in the serum or the plasma of the patients, and correlates with extensive bone disease and adverse myeloma features. In prostate cancer, sclerostin expression is reduced and in combination with bone morhogenetic protein-6 and noggin expression may serve as prognostic predictor for metastatic progression. In breast cancer, in vitro data suggest that the malignant cell induces the expression of sclerostin to inhibit osteoblasts in the metastatic bone area. Expert opinion: Sclerostin may play a role in inhibiting bone formation in the biology of bone metastases in breast cancer and of myeloma-related bone disease. The results of phase I/II studies with anti-sclerostin drugs in subjects with low bone mass may lead to the potential clinical investigation of these agents in cancer-indauced bone disease. © 2012 Informa UK, Ltd.

Many studies have shown that patients with Alzheimer's disease (AD) are at increased risk for developing seizures and epilepsy. However, reported prevalence and incidence of seizures and relationship of seizures to disease measures such as severity, outcome, and progression vary widely between studies. We performed a literature review of the available clinical and epidemiological data on the topic of seizures in patients with AD. We review seizure rates and types, risk factors for seizures, electroencephalogram (EEG) studies, and treatment responses. Finally, we consider limitations and methodological issues. There is considerable variability in the reported prevalence and incidence of seizures in patients with AD-with reported lifetime prevalence rates of 1.5-64%. More recent, prospective, and larger studies in general report lower rates. Some, but not all, studies have noted increased seizure risk with increasing dementia severity or with younger age of AD onset. Generalized convulsive seizures are the most commonly reported type, but often historical information is the only basis used to determine seizure type and the manifestation of seizures may be difficult to distinguish from other behaviors common in demented patients. EEG has infrequently been performed and reported. Data on treatment of seizures in AD are extremely limited. Similarly, the relationship between seizures and cognitive impairment in AD is unclear. We conclude that the literature on seizures and epilepsy in AD, including diagnosis, risk factors, and response to treatment suffers from methodological limitations and gaps.

Alzheimer disease (AD) and epilepsy are disorders commonly seen in the elderly. Many studies have shown that patients with AD are at increased risk for developing seizures and epilepsy. Whereas, patients with specific types of epilepsy, such as temporal lobe epilepsy (TLE), experience some degree of cognitive dysfunction, questions have been raised as to whether these disorders share some underlying pathophysiologic mechanisms or whether one is an epiphenomenon of the other. In this report, we review some of the available clinical and epidemiologic literature on various aspects of the topic of seizures in AD, including seizure rates and types, risk factors for seizures, electroencephalographic findings, treatment options, limitations, and methodological issues. Overall, multiple aspects of the literature on seizures and epilepsy in AD, including diagnosis, risk factors, the role of EEG in diagnosis, and the response to treatment are not clear and suffer from many methodological limitations and gaps.

Self-ordered 1D nanostructures currently attract increasing interest due to their controlled geometry associated with unique structural and morphological characteristics. Vertically oriented TiO2 nanotubes (NTs) grown by electrochemical anodization provide a robust substrate for efficient solar-energy conversion. In this work, we report on the preparation of NTs under low applied voltage (+30 V vs. Pt) in NH4F/ethylene glycol electrolytes containing a slight amount of water. The effects of the Ti foils polishing (before anodization) and the removal of the nanograss (structural disorder created at the top surface of the NTs due to the prolonged exposure of the tubes inside the F- rich environment) on the nanotubular films properties are investigated. After optimization of the anodization conditions, homogeneous anodic films consisting of smooth and long NTs are prepared, which, when incorporated as photoelectrodes in dye-sensitized solar cells, present an overall power conversion efficiencies of about 3% under backside illumination conditions. © 2011 Elsevier B.V. All rights reserved.

Sorafenib and sunitinib are inhibitors of receptor protein tyrosine kinases (TKIs) and are approved for the treatment of metastatic renal cell carcinoma (mRCC). Although the mTOR inhibitor everolimus is effective for the treatment of patients who have failed TKI therapy, it is important to consider all available treatment options before switching therapy mode of action. Herein, we report outcomes in patients with mRCC switched to sorafenib following disease progression on sunitinib treatment. The medical records of 35 patients treated between November 2006 and November 2009 at two large referral centers in Greece were retrospectively analyzed for time-to-progression (TTP), overall survival (OS), and tolerability of sorafenib after sunitinib. Median TTP and OS on sorafenib were 4.9 and 11.5 months, respectively. Among 33 patients evaluable for tumor response, three had a partial response and 17 achieved disease stabilization (objective response rate 8.5%; total clinical benefit rate 57%). Sorafenib was well tolerated, with mostly grade 1/2 adverse events and no treatment-related deaths. Sorafenib was effective and well tolerated in this group of patients. The TTP with sorafenib following sunitinib was comparable to outcomes reported previously, providing further support that TKIs should be used in sequence before switching to an mTOR inhibitor. © Springer Science+Business Media, LLC 2011.

The rat Forced Swim Test (FST) is widely used to investigate the response to antidepressant treatment. Selective serotonin reuptake inhibitors (SSRIs) elongate swimming duration during the FST, while climbing duration is unaffected. In the present study, we aimed to correlate behavioral effects of the SSRI sertraline in the FST with respective changes in the serotonergic activity of the hippocampus and the prefrontal cortex. Male rats were subjected to the standard FST (two swim sessions in two consecutive days) and between the two sessions they received three i.p. injections of sertraline (10 mg/kg or 40 mg/kg) or vehicle. All rats were killed immediately after the second FST session. Unstressed animals received the same administration schemes and were killed in equivalent time-points. Serotonin and its metabolite 5-HIAA were assayed in the hippocampus and the prefrontal cortex with the use of high-performance liquid chromatography (HPLC-ED) and their ratio 5-HIAA/5-HT was calculated. Sertraline enhanced swimming and decreased immobility duration at both doses. Serotonergic activity was not altered by the 2-day swim stress in either brain region, while subchronic sertraline treatment enhanced 5-HT levels and decreased 5-HIAA/5-HT in the hippocampus and the prefrontal cortex. The serotonin turnover rate (5-HIAA/5-HT ratio) decrease is probably indicative of reduced 5-HT metabolism, as a result of 5-HT reuptake inhibition. This effect was significant in the prefrontal cortex of unstressed rats only after a higher dose of sertraline. In the prefrontal cortex, but not in the hippocampus, immobility duration was negatively correlated with 5-HT tissue levels, whereas swimming duration was positively correlated with 5-HT. These results indicate that after antidepressant treatment, behavior during the FST can be predictive of respective serotonergic changes, especially in the prefrontal cortex.

The rat Forced Swim Test (FST) is widely used to investigate the response to antidepressant treatment. Selective serotonin reuptake inhibitors (SSRIs) elongate swimming duration during the FST, while climbing duration is unaffected. In the present study, we aimed to correlate behavioral effects of the SSRI sertraline in the FST with respective changes in the serotonergic activity of the hippocampus and the prefrontal cortex. Male rats were subjected to the standard FST (two swim sessions in two consecutive days) and between the two sessions they received three i.p. injections of sertraline (10 mg/kg or 40 mg/kg) or vehicle. All rats were killed immediately after the second FST session. Unstressed animals received the same administration schemes and were killed in equivalent time-points. Serotonin and its metabolite 5-HIAA were assayed in the hippocampus and the prefrontal cortex with the use of high-performance liquid chromatography (HPLC-ED) and their ratio 5-HIAA/5-HT was calculated. Sertraline enhanced swimming and decreased immobility duration at both doses. Serotonergic activity was not altered by the 2-day swim stress in either brain region, while subchronic sertraline treatment enhanced 5-HT levels and decreased 5-HIAA/5-HT in the hippocampus and the prefrontal cortex. The serotonin turnover rate (5-HIAA/5-HT ratio) decrease is probably indicative of reduced 5-HT metabolism, as a result of 5-HT reuptake inhibition. This effect was significant in the prefrontal cortex of unstressed rats only after a higher dose of sertraline. In the prefrontal cortex, but not in the hippocampus, immobility duration was negatively correlated with 5-HT tissue levels, whereas swimming duration was positively correlated with 5-HT. These results indicate that after antidepressant treatment, behavior during the FST can be predictive of respective serotonergic changes, especially in the prefrontal cortex.

BACKGROUND: Pathologic collagen remodeling has been involved in the occurrence of ventricular arrhythmias and sudden cardiac death in heart failure. The aim of the study was to investigate the relationship between malignant ventricular arrhythmias and cardiac collagen turnover indexes, expressing specific types of derangement in collagen physiology, in stable patients with an implantable cardioverter-defibrillator (ICD). METHODS: Seventy-four patients with an ICD and heart failure were studied. They had coronary artery disease (n = 42) or dilated cardiomyopathy, New York Heart Association classes I and II, and left ventricular ejection fraction 29% +/- 1%. An ICD had been implanted for secondary (n = 36) or primary prevention of sudden cardiac death. We assessed (1) markers of collagen types I and III synthesis and their ratio: procollagen type I carboxyterminal peptide (PICP), procollagen type III aminoterminal peptide (PIIINP), and PICP/PIIINP; (2) markers of collagen degradation, degradation inhibition, and their ratio: matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase (TIMP) 1 (TIMP-1), and MMP-9/TIMP-1. Patients were prospectively followed up for 1 year. The number of episodes necessitating appropriate interventions for ventricular tachyarrhythmias (>170 beat/min) was related to the assessed parameters. RESULTS: Multivariate analysis revealed a significant relation between the number of tachyarrhythmic episodes and MMP-9/TIMP-1 (P = .007), PICP/PIIINP (P = .007), and ejection fraction (P = .04). No other significant relation was observed between arrhythmias and the remaining parameters. CONCLUSION: In heart failure, biochemical markers indicative of a deranged equilirium in myocardial collagen deposition/degradation and collagen I/III synthesis are related to ventricular arrhythmogenesis. Further studies are needed to investigate their predictive ability

The application of a procedure based on XAD-4 adsorption resin permitted the obtainment of an enriched polyphenolic extract from Sesamum indicum seeds. Chemical analysis of the obtained extract led to the identification of 12 lignans. Among them, 2 lignans, (+)-sesamolinol-4'-O-β-d-glucoside and disaminyl ether, are reported for the first time as natural compounds. Their structure has been determined by spectroscopic methods, mainly by the application of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) techniques [heteronuclear multiple-quantum coherence (HMQC), heteronuclear multiple-bond correlation (HMBC), and nuclear Overhauser effect spectrometry (NOESY)] and mass spectroscopy. The isolated compounds were evaluated for their antimutagenic activity. Among the tested lignans, the most active lignan was found to be sesamolin, followed by sesamolinol and samin, against H2O2. Additionally, some of the tested lignans showed desmutagenic activity against benzo[a]pyrene (BaP). © 2011 American Chemical Society.

Artificial Neural Network (ANN) models were developed and applied in order to predict the total weekly number of Childhood Asthma Admission (CAA) at the greater Athens area (GAA) in Greece. Hourly meteorological data from the National Observatory of Athens and ambient air pollution data from seven different areas within the GAA for the period 2001-2004 were used. Asthma admissions for the same period were obtained from hospital registries of the three main Children's Hospitals of Athens. Three different ANN models were developed and trained in order to forecast the CAA for the subgroups of 0-4, 5-14-year olds, and for the whole study population. The results of this work have shown that ANNs could give an adequate forecast of the total weekly number of CAA in relation to the bioclimatic and air pollution conditions. The forecasted numbers are in very good agreement with the observed real total weekly numbers of CAA. © 2012 Taylor & Francis.

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.

Intercellular adhesion molecule-1 (ICAM-1), a cell adhesion molecule with a key role in inflammation and immunosurveillance, has been implicated in carcinogenesis by facilitating instability of the tumor environment. The K469E single nucleotide polymorphism (SNP) (G>A) affects the ICAM-1 mRNA splicing pattern; the alternatively spliced isoform (ICAM-1-S) lacks transmembrane and intracellular domain, which affects the structural and signal transduction properties. Moreover, the expression of ICAM-1 is transcriptionally regulated by p53, and this SNP has been shown to be related with apoptosis. PCR-RFLP analysis was used to assess the K469E SNP status comparatively in 203 non-small cell lung cancer patients and 175 healthy sex-matched controls. This SNP was examined in relation to tumor kinetic parameters (Ki-67 immunohistochemical evaluation and Tdt-mediated dUTP nick end labeling assay), p53 immunohistochemistry status, and clinicopathological data in patients with operable stages. Both the genotype and allele frequency did not differ significantly between patients and controls. However, patients with the AG/AA genotypes had worse survival (39 vs 45 months, p = 0.036) and tended to be present in advanced stages (p = 0.057). Moreover, the AG/AA genotypes exerted a synergistic effect with aberrant p53 on tumor progression, while the GG genotype retained a better apoptotic index. The AG/AA genotypes correlated with worse survival and advanced stages probably due to defective immunosurveillance and apoptosis. These genetic backgrounds may confer a selective advantage for dissemination of tumor cells with high metastatic potential compared to GG genotype.

The concept of Social Media is at the top of the agenda of many entrepreneurs, business executives and decision makers today. This paper examines the new media and digital culture which has become an important part of our daily activities, using the social network perspective, a theoretical concept as used in the social and behavioural sciences. This theoretical perspective allows us to identify the dynamics of social networks: the concept of social media today, for many a new and stimulating environment and for others a social space that evokes feelings of frustration or fear of losing touch with the real world. Are women equipped to thrive in this digital age and especially in this virtual environment? In examining current research findings on social women, new models of work, levels of engagement, transformational leadership styles and women entrepreneurs that have been de-mystifying the world of social media through the lens of their own experiences, this paper argues that women enjoy a slight edge over their male counterparts and that today’s business climate is more inviting for aspiring women entrepreneurs. The bottom line is that social women are doing what most women do "naturally", namely creating relationships, community, connections and support. Isn’t that what social networking is all about? Social women share content in multiple ways and working online has been a financial windfall for many, including stay at home moms and homemakers. Finally, this paper presents tips and advice from successful women entrepreneurs who tell how they have been using social media to excel in their careers and balance their career/family/personal lives.   Keywords: new media, social media, social networking, technology as an enabler, integrating a gender perspective, “feminine” skills and leadership qualities  

In this study, we provide the first evidence of two pairs of petals of the rapidly expanded and short-lived nocturnal flowers of Capparis spinosa L. (caper) during the prolonged drought period in Eastern Mediterranean region. The corolla of the winter-deciduous, perennial C. spinosa consists of two pairs of petals: a pair of white distinct petals and a pair of connate variegated petals with green basal parts. The results indicated the presence of substantially different amounts of chlorophyll in the two pairs of petals, while their carbohydrates’ content is comparable with that of the green sepals. High resolution imaging of petal surfaces of short-lived flowers of C. spinosa, obtained by using scanning electron microscopy, revealed stomata on the adaxial epidermis on both the white and the green parts of the variegated petals; while dense hairs were found on the surface of the abaxial green parts of the variegated petals. Adaxial, epidermal cells of the variegated petals, viewed using atomic force microscopy, possess a submicron, cuticular microfolding that differs between the white and the green parts of the petals. It appears that microridges on the adaxial, white parts of petals of C. spinosa compensate for an increase in cell surface area of the short lived petals, while the roughness of the green parts of petals was found to be higher than that of the white parts. Thus, the micromorphology of surfaces of epidermal cells is expected to affect optical properties and wettability of the floral tissues. These findings may be particularly important for understanding the performance of the short-lived petals of C. spinosa, which are exposed to dryland environments.

Because of its pivotal role in the recycling pathway allowing NAD generation from nicotinamide, NAMPT occupies a central position in controlling the activity of several NAD-dependent enzymes. NAD, a universal energy-and signal-carrying molecule and its phosphorylated form, NADP, are required in several intracellular processes such as redox reactions, DNA repair, G-protein coupled receptor signaling, intra-cellular calcium-mobilizing molecules, transcriptional regulation, mono-adenosine diphosphate (ADP)-ribosylation in immune response, and activity of poly-ADP ribosyltransferases and deacetylases (sirtuins) with roles in regulating cell survival and cytokine responses. Under the influence of NAMPT, adequate levels of NAD control SIRT-6 (sirtuin) activity, which in turn positively regulates TNF-α mRNA translation favoring cell survival. NAMPT activity enhances cellular proliferation, tips the balance toward cellular survival following a genotoxic insult and controls the circadian clock machinery of some key transcriptions factors.

We report on the structural and optical characterization of two-dimensional arrays of silicon nanocrystals (SiNCs) suitable for photovoltaic applications. Single and multiple SiNC layers were grown on quartz by low pressure chemical vapor deposition of Si and subsequent thermal oxidation steps. The single SiNC layers consisted of one SiNC layer embedded in two silicon dioxide (SiO 2) layers, whereas the multi-layered structure consisted of five SiNC layers of equal thickness separated by SiO 2 layers. SiNC layers with thicknesses ranging from 2 to 25 nm were investigated. A thorough structural characterization of the films was carried out by combining grazing incidence x-ray diffraction, x-ray reflectivity, and transmission electron microscopy (TEM). Both XRD and TEM measurements revealed that the SiNC layers were polycrystalline in nature and composed of SiNCs, separated by grain boundaries, with their vertical size equal to the SiNC layer and their lateral size characterized by a narrow size distribution. The high resolution TEM (HRTEM) images showed that oxidation of the SiNC layers proceeded by consumption of Si from their top surface, without any detectable oxidation at the grain boundaries. Only in the case of the thinnest investigated SiNC layer (2 nm), the SiNCs were well separated by SiO 2 tunnel barriers. From transmission and reflection optical measurements, energy band gaps of the SiNCs were estimated. These results were correlated with the sizes of the SiNCs obtained by HRTEM. A shift of the estimated band gaps with decreasing SiNC size was observed. This was consistent with quantum size effects in the SiNCs. The film containing the smallest SiNCs (2 nm in the growth direction), besides a significant shift of the absorption edge to higher energies, showed light emission at room temperature which is due to radiative recombination of photo-generated carriers in localized SiNCs separated by SiO 2 tunnel barriers. © 2012 American Institute of Physics.

The structural and magnetic properties and spin dynamics of dextran coated and uncoated gamma-Fe2O3 (maghemite) nanoparticles have been investigated using high resolution transmission electron microscopy (HRTEM), Fe-57 nuclear magnetic resonance (NMR), Mossbauer spectroscopy and dc magnetization measurements. The HRTEM observations indicated a well-crystallized system of ellipsoid-shaped nanoparticles, with an average size of 10 nm. The combined Mossbauer and magnetic study suggested the existence of significant interparticle interactions not only in the uncoated but also in the dextran coated nanoparticle assemblies. The zero-field NMR spectra of the nanoparticles at low temperatures are very similar to those of the bulk material, indicating the same hyperfine field values at saturation in accord with the performed Mossbauer measurements. The T-2 NMR spin-spin relaxation time of the nanoparticles has also been measured as a function of temperature and found to be two orders of magnitude shorter than that of the bulk material. It is shown that the thermal fluctuations in the longitudinal magnetization of the nanoparticles in the low temperature limit may account for the shortening and the temperature dependence of the T-2 relaxation time. Thus, the low temperature NMR results are in accord with the mechanism of collective magnetic excitations, due to the precession of the magnetization around the easy direction of the magnetization at an energy minimum, a mechanism originally proposed to interpret Mossbauer experiments in magnetic nanoparticles. The effect of the surface spins on the NMR relaxation mechanisms is also discussed.

Detailed mapping along the coasts of Skyros Island (Aegean Sea) provided new evidence concerning the rates and the modality of subsidence in the area. The results are provided through the study of the shape and the dimensions of the two submerged notches detected around the carbonate coasts of the island.It is apparent that the island has been submerged not only due to the global sea-level rise during the last two centuries (1.8 ± 0.3 mm/year between 1950 and 2000), but also because of tectonic events testified by the type of the submerged notches. Some of these tectonic events seem to be of gradual and some of co-seismic origin. The transition of MSL from the retreat point of the lower notch to the retreat point of the upper notch seems to have been produced by co-seismic subsidence of about 55 cm at slightly less than 850 years BP.

Active muscles generate substantial mechanical forces by the contraction/relaxation cycle, and, to maintain an ordered state, they require molecular structures of extraordinary stability. These forces are sensed and buffered by unusually long and elastic filament proteins with highly repetitive domain arrays. Members of the myomesin protein family function as molecular bridges that connect major filament systems in the central M-band of muscle sarcomeres, which is a central locus of passive stress sensing. To unravel the mechanism of molecular elasticity in such filament-connecting proteins, we have determined the overall architecture of the complete C-terminal immunoglobulin domain array of myomesin by X-ray crystallography, electron microscopy, solution X-ray scattering, and atomic force microscopy. Our data reveal a dimeric tail-to-tail filament structure of about 360 A in length, which is folded into an irregular superhelical coil arrangement of almost identical alpha-helix/domain modules. The myomesin filament can be stretched to about 2.5-fold its original length by reversible unfolding of these linkers, a mechanism that to our knowledge has not been observed previously. Our data explain how myomesin could act as a highly elastic ribbon to maintain the overall structural organization of the sarcomeric M-band. In general terms, our data demonstrate how repetitive domain modules such as those found in myomesin could generate highly elastic protein structures in highly organized cell systems such as muscle sarcomeres.

Context. We present the analysis of supernova remnants (SNRs) and candidates in M 31 identified in the XMM-Newton large programme survey of M 31. Supernova remnants are among the brightest X-ray sources in a galaxy. They are good indicators of the recent star-formation activities of galaxies and the interstellar environment in which they evolve. Aims: By combining the X-ray data of sources in M 31 with optical data as well as optical and radio catalogues, we aim to compile a complete, revised list of SNRs emitting X-rays in M 31 detected with XMM-Newton, study their luminosity and spatial distributions, and understand the X-ray spectra of the brightest SNRs. Methods: We analysed the X-ray spectra of the 12 brightest SNRs and candidates that have been observed with XMM-Newton. Our study of the four brightest sources allowed us to perform a more detailed spectral analysis and compare different models to describe their spectrum. For all M 31 large programme sources, we searched for their optical counterparts in the Hα, [S ii], and [O iii] images of the Local Group Galaxy Survey. Results: We confirm 21 X-ray sources as counterparts to known SNRs. In addition, we identify 5 new X-ray sources as X-ray and optically emitting SNRs. Seventeen sources are no longer considered as SNR candidates. We thus create a list of 26 X-ray SNRs and 20 X-ray SNR candidates in M 31 based on their X-ray, optical, and radio emission, which is the most recent complete list of X-ray SNRs in M 31. The brightest SNRs have X-ray luminosities of up to 8 × 1036 erg s-1 in the 0.35-2.0 keV band. Based on observations obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States and NASA.Appendices are available in electronic form at http://www.aanda.org

BACKGROUND: Palliative surgery followed by postoperative chemotherapy is a challenging approach in the treatment of stage IV gastric cancer yet patients must be carefully selected on the basis of likely clinical benefit. METHODS: The records of 218 patients with histological diagnosis of gastric adenocarcinoma who underwent palliative surgery followed by postoperative chemotherapy were retrospectively reviewed. Twelve potential prognostic variables including tumour DNA index and serum IgG anti- Helicobacter pylori (HP) antibodies were evaluated for their influence on overall survival by multivariate analysis. RESULTS: The median survival was 13.25 months [95% Confidence Interval (CI) 12.00, 14.50]. Three factors were found to have an independent effect on survival: performance status (PS) [PS 60-70 vs. 90-100 Hazard Ratio (HR) 1.676; CI 1.171-2.398, p = 0.005], liver metastases (HR 1.745; CI 1.318-2.310, p < 0.001), and DNA Index as assessed by Image cytometry (2.2-3.6 vs. >3.6 HR 3.059; CI 2.185-4.283, p < 0.001 and <2.2 vs. >3.6 HR; 4.207 CI 2.751-6.433 <0.001). HP infection had no statistically significant effect on survival by either univariate or multivariate analysis. CONCLUSION: Poor pre-treatment PS, the presence of liver metastasis and high DNA Index were identified factors associated with adverse survival outcome in patients with Stage IV gastric cancer treated with palliative gastrectomy and postoperative chemotherapy. HP infection had no influence on survival of these patients.

Core/shell particles were synthesized by assembling oppositely charged ferrite (Fe3O4 or NiFe2O4) nanoparticles on the surface of monodispersed silica core particles (having size similar to 0.4 mu m) prepared by hydrolysis and condensation of tetraethylortosilicate. Optimal conditions for synthesis of silica core/nano-Fe3O4 shell particles were found at pH similar to 5.4. The obtained particles have superparamagnetic behavior above a blocking temperature of approximate to 25 K, which make them very attractive for a broad range of biomedical and bioengineering applications. Incorporation of nickel into ferrite structure could not be achieved at lower pH value, so functionalization of core particles was required. Incorporation of nickel into ferrite structure was successful at pH above 7, however at higher pH the formation rate of nickel-ferrite particles becomes very fast and the self-aggregation dominates the competing formation of the nickel-ferrite shell. Because of that the self-aggregation was prevented by surface modification of nickel-ferrite nanoparticles with citric acid before their deposition on the functionalized silica core and homogenous and continuous NiFe2O4 shell was finally obtained. (C) 2012 Elsevier Ltd. All rights reserved.

Starting from cis-[Ru(dcbpyH 2) 2Cl 2] (1), two new heteroleptic ruthenium(II) complexes, [Ru(dcbpyH 2) 2(L 1)](NO 3) 2 (L 1=2- (2′-pyridyl)quinoxaline (2), and [Ru(dcbpyH 2) 2(L 2)](NO 3) 2 (L 2=4- carboxy-2-(2′-pyridyl)quinoline (4); dcbpyH 2=2,2′- bipyridine-4,4′-dicarboxylic acid), were synthesized and spectroscopically characterized. During the preparation of 2 and 4, the homoleptic [Ru(dcbpyH 2) 3]Cl 2 complex (3) was isolated as a side product. Characterization includes IR and Raman spectroscopy, UV-Vis, multinuclear NMR spectroscopy, elemental, and ESI-mass spectrometric analyses. © 2012 Taylor and Francis.

We have demonstrated heterogeneous photocatalytic degradation of microcystin-LR (MC-LR) by visible light activated carbon doped TiO 2 (C-TiO 2) nanoparticles, synthesized by a modified sol-gel route based on the self-assembly technique exploiting oleic acid as a pore directing agent and carbon source. The C-TiO 2 nanoparticles crystallize in anatase phase despite the low calcination temperature of 350°C and exhibit a highly porous structure that can be optimized by tuning the concentration of the oleic acid surfactant. The carbon modified nanomaterials exhibited enhanced absorption in the broad visible light region together with an apparent red shift in the optical absorption edge by 0.5eV (2.69eV), compared to the 3.18eV of reference anatase TiO 2. Carbon species were identified by x-ray photoelectron spectroscopy analysis through the formation of both Ti-C and C-O bonds, indicative of substitution of carbon for oxygen atoms and the formation of carbonates, respectively. Electron paramagnetic resonance spectroscopy revealed the formation of two carbon related paramagnetic centers in C-TiO 2, whose intensity was markedly enhanced under visible light illumination, pointing to the formation of localized states within the anatase band gap, following carbon doping. The photocatalytic activity of C-TiO 2 nanomaterials was evaluated for the degradation of MC-LR at pH 3.0 under visible light (λ>420nm) irradiation. The doped materials showed a higher MC-LR degradation rate than reference TiO 2, behavior that is attributed to the incorporation of carbon into the titania lattice. © 2012 IOP Publishing Ltd.

The aim of this paper is to provide further information of the tafoni development. At Theologos area, Fthiotis Prefecture, north Euboean Gulf, a carbonate formation hosts a variety of well developed tafoni. 165 tafoni were, randomly, selected by means of a detailed geomorphological investigation. The presence or absence of lichen cover, rock flaking, and cavern floor debris, amalgamation, salt flakes, different kind of structures, biological communities, were noted, while measurements regarding their dimension took place. Surface hardness values, obtained using a Schmidt hammer. Although, there is no evidence of the key factor that drives the growth of tafoni, salt weathering and low strength seems determinant of their formation. Moreover, much of the evidences suggest that joints are actively influencing the origin and the morphology of tafoni. It is possible that tafoni formation is initiated at weak zones. The studied tafoni are actively developing and are not relict features inherited from a past environment. It seems that their evolutionary stage is II towards to III. The results of chemical and mineralogical analysis indicate that during the cavernous weathering, silica, sulphates, alumina and iron oxides have replaced carbonate grains. Also, at the non-weathered part of the rock, the main mineralogical phases are calcite and dolomite.

Background: Perioperative transfusion optimization may result in blood saving and minimization of complications associated with blood transfusions. The study aimed to compare units transfused, cytokines and patient outcome in a restrictive versus a liberal transfusion strategy. Materials and methods: We conducted a randomized-controlled study, in a single center, from December 2004 to May 2007. Of the 75 patients scheduled for major abdominal surgery and assessed for eligibility, 58 were randomized and 52 completed the study. Preoperatively, patients were randomly assigned to the Hb 7.7 g dL-1 (restrictive) or to the Hb 9.9 g dL-1 (liberal) group to receive blood transfusion intraoperatively and postoperatively if hemoglobin was below 7.7 g dL-1 or Hb 9.9 g dL-1 respectively. The follow-up for hemoglobin and intervention lasted five days, for cytokine measurements three days and for complications till discharge from the hospital. Units of red blood cells (RBC) per patient and the incidence of transfused patients in each group were the main outcome measure. Results: Median RBC transfused (units/patient) was 0 [interquartile range 0,2] in the restrictive versus 1 [0,3] in the liberal group (p=0.013), and the percentage of patients transfused 36% versus 70% respectively (p=0.027). Postoperative IL-10 levels were higher in the liberal transfusion group 24 h postoperatively (p<0.05). Pooled peak postoperative IL-10 levels correlated with the overall number of units of blood transfused (r2 = 0.38, p = 0.032) as well as with the overall mean duration of storage of blood transfused (in days) (r2 = 0.52, p = 0.007). Complications or time to discharge from hospital did not differ between the groups. Conclusion: In major abdominal surgery, restrictive transfusion decreases RBC requirements and IL-10 levels. The association between IL-10 and transfusion variables indicates that IL-10 may play a role in transfusionassociated immunomodulation. © 2012 Markatou M, et al.

Extracellular matrices (ECMs) are dynamic structures that provide cells not only with a structural support but, importantly, exhibit significant functional roles in the control of key cellular events such as adhesion, migration, proliferation, differentiation, and survival. In tumors, matrix effectors such as proteoglycans (PGs) and matrix metalloproteinases (MMPs) constitute major regulators of the interactions between tumor cells and their microenvironment and, therefore, they have been identified as potential molecular targets that are expected to advance the pharmacological treatment of cancer. ECMs composition is highly affected by cells through intrinsic regulatory mechanisms, such as the ubiquitin-proteasome system (UPS). Proteasome is a major cellular protease complex that controls the concentration and turnover of molecules in ECMs, including certain types of PGs, MMPs and collagens, and consequently, in the tumor microenvironment. Furthermore, proteasome activity is regulated by PG-derived intracellular glycosaminoglycan moieties revealing a critical inter-dependence of these compounds. Since ECMs renewal and degradation can be tightly regulated by proteasome activities, its modulation may be considered as a novel strategy to control the properties of tumor microenvironment. Currently, there are several proteasome inhibitors targeting distinct molecular pathways either approved or in clinical trials for the treatment of multiple cancers. In this review, the novel approach of targeting the proteasome to selectively regulate the synthesis and the bioactivity of certain matrix PGs and MMPs is presented and discussed.

The present article reports a study concerning the analysis of 19 activity plans (we call them ‘scenarios’) developed by mathematics teacher educators-in-training for the pedagogical use of digital tools. The development of these scenarios took place during their training program and it was designed as an activity for increasing reflection, for expressing creative pedagogical ideas and for an active engagement in the design of curricula enriched with the use of technology. Our analysis shows that the trainee teacher educators deconstructed and reconstructed respective parts of the formal curriculum regarding the mathematical concepts they chose to embody in their scenarios.

The hadronic model of active galactic nuclei and other compact high-energy astrophysical sources assumes that ultra-relativistic protons, electron-positron pairs and photons interact via various hadronic and electromagnetic processes inside a magnetized volume, producing the multiwavelength spectra observed from these sources. A less studied property of such systems is that they can exhibit a variety of temporal behaviours due to the operation of different feedback mechanisms. We investigate the effects of one possible feedback loop, where γ-rays produced by photopion processes are being quenched whenever their compactness increases above a critical level. This causes a spontaneous creation of soft photons in the system that result in further proton cooling and more production of γ-rays, thus making the loop operate. We perform an analytical study of a simplified set of equations describing the system, in order to investigate the connection of its temporal behaviour with key physical parameters. We also perform numerical integration of the full set of kinetic equations verifying not only our analytical results but also those of previous numerical studies. We find that once the system becomes 'supercritical', it can exhibit either a periodic behaviour or a damped oscillatory one leading to a steady state. We briefly point out possible implications of such a supercriticality on the parameter values used in active galactic nuclei spectral modelling, through an indicative fitting of the VHE emission of blazar 3C 279.

The hadronic model of active galactic nuclei and other compact high-energy astrophysical sources assumes that ultra-relativistic protons, electron-positron pairs and photons interact via various hadronic and electromagnetic processes inside a magnetized volume, producing the multiwavelength spectra observed from these sources. A less studied property of such systems is that they can exhibit a variety of temporal behaviours due to the operation of different feedback mechanisms. We investigate the effects of one possible feedback loop, where γ-rays produced by photopion processes are being quenched whenever their compactness increases above a critical level. This causes a spontaneous creation of soft photons in the system that result in further proton cooling and more production of γ-rays, thus making the loop operate. We perform an analytical study of a simplified set of equations describing the system, in order to investigate the connection of its temporal behaviour with key physical parameters. We also perform numerical integration of the full set of kinetic equations verifying not only our analytical results but also those of previous numerical studies. We find that once the system becomes 'supercritical', it can exhibit either a periodic behaviour or a damped oscillatory one leading to a steady state. We briefly point out possible implications of such a supercriticality on the parameter values used in active galactic nuclei spectral modelling, through an indicative fitting of the VHE emission of blazar 3C 279.

Test abstract

THAP1 mutations have been shown to be the cause of DYT6. A number of different mutation types and locations in the THAP1 gene have been associated with a range of severity and dystonia phenotypes, but, as yet, it has been difficult to identify clear genotype phenotype patterns. Here, we screened the THAP1 gene in a further series of dystonia cases and evaluated the mutation pathogenicity in this series as well as previously reported mutations to investigate possible phenotype-genotype correlations. THAP1 mutations have been identified throughout the coding region of the gene, with the greatest concentration of variants localized to the THAP1 domain. In the additional cases analyzed here, a further two mutations were found. No obvious, indisputable genotype-phenotype correlation emerged from these data. However, we managed to find a correlation between the pathogenicity of mutations, distribution, and age of onset of dystonia. THAP1 mutations are an important cause of dystonia, but, as yet, no clear genotype-phenotype correlations have been identified. Greater mutation numbers in different populations will be important and mutation-specific functional studies will be essential to identify the pathogenicity of the various THAP1 mutations. © 2012 Movement Disorder Society.

Background/Aims: The transmission rate of air-borne infectious diseases may vary secondary to climate conditions. The study assessed time trends in the seasonality of hospitalized varicella cases in a temperate region in relation to climatic parameters prior to the implementation of universal varicella immunization. Methods: A retrospective descriptive study was conducted among all pediatric and adolescent varicella patients (n = 2366) hospitalized at the "Aghia Sophia" Children's Hospital during 1982-2003 in Athens, Greece. Date of infection was computed based on hospital admission date. Seasonal and monthly trends in the epidemiology of varicella infection were assessed with time series analysis (ARIMA modeling procedure). The correlation between the frequency of varicella patients and the meteorological parameters was examined by the application of Generalized Linear Models with Gamma distribution. Results: During 1982-2003, the occurrence of hospitalized varicella cases increased during summer (p = 0.025) and decreased during autumn (p = 0.021), and particularly in September (p = 0.003). The frequency of hospitalized varicella cases was inversely associated with air temperature (p<0.001). In contrast, the occurrence of hospitalized varicella cases was positively associated with wind speed (p = 0.009). Conclusions: Pediatric hospitalizations for varicella infection rates have increased during summer and decreased during autumn in the examined temperate region. Time trends in hospitalized varicella cases are associated with climatic variables. © 2012 Critselis et al.

We present a time-dependent approach to the one-zone hadronic model in the case where the photon spectrum is produced by ultrarelativistic protons interacting with soft photons that are produced from protons and low magnetic fields. Assuming that protons are injected at a certain rate in a homogeneous spherical volume containing a magnetic field, the evolution of the system can be described by five coupled kinetic equations, for protons, electrons, photons, neutrons, and neutrinos. Photopair and photopion interactions are modelled using the results of Monte-Carlo simulations and, in particular, from the SOPHIA code for the latter. The coupling of energy losses and injection introduces a self-consistency in our approach and allows the study of the comparative relevancy of processes at various conditions, the efficiency of the conversion of proton luminosity to radiation, the resulting neutrino spectra, and the effects of time variability on proton injection, among other topics. We present some characteristic examples of the temporal behaviour of the system and show that this can be very different from the one exhibited by leptonic models. Furthermore, we argue that, contrary to the wide-held belief, there are parameter regimes where the hadronic models can become quite efficient. However, to keep the free parameters at a minimum and facilitate an in-depth study of the system, we have only concentrated on the case where protons are injected; i.e., we did not consider the effects of a co-accelerated leptonic component.

BACKGROUND: Carbapenemase-producing Klebsiella pneumoniae (CPKP) has been established as important nosocomial pathogen in many geographic regions. Transmission from patient to patient via the hands of healthcare workers is the main route of spread in the acute-care setting. METHODOLOGY/PRINCIPAL FINDINGS: Epidemiological and infection control data were recorded during a prospective observational study conducted in a surgical unit of a tertiary-care hospital in Greece. Surveillance culture for CPKP were obtained from all patients upon admission and weekly thereafter. The Ross-Macdonald model for vector-borne diseases was applied to obtain estimates for the basic reproduction number R(0) (average number of secondary cases per primary case in the absence of infection control) and assess the impact of infection control measures on CPKP containment in endemic and hyperendemic settings. Eighteen of 850 patients were colonized with CPKP on admission and 51 acquired CPKP during hospilazation. R(0) reached 2 and exceeded unity for long periods of time under the observed hand hygiene compliance (21%). The minimum hand hygiene compliance level necessary to control transmission was 50%. Reduction of 60% to 90% in colonized patients on admission, through active surveillance culture, contact precautions and isolation/cohorting, in combination with 60% compliance in hand hygiene would result in rapid decline in CPKP prevalence within 8-12 weeks. Antibiotics restrictions did not have a substantial benefit when an aggressive control strategy was implemented. CONCLUSIONS/SIGNIFICANCE: Surveillance culture on admission and isolation/cohorting of colonized patients coupled with moderate hand hygiene compliance and contact precautions may lead to rapid control of CPKP in endemic and hyperendemic healthcare settings.

This study analyses the Saharan dust (SD) events over Athens during 2000-2005 using daily Moderate Resolution Imaging Spectroradiometer (MODIS) and Total Ozone Mapping Spectrometer (TOMS) satellite data. The dust events were identified using the MODIS daily observations over Greece and the dates with detectable dust plumes were collected. The aerosol optical depth (AOD 550) and fine-mode (FM) values from Terra-MODIS and Aerosol Index (AI) values from TOMS were obtained over Athens for the dusty days focusing on analysing the seasonality, intensity, transport pathways and mechanisms of dust. Seventy-nine dusty days were identified corresponding to SD events with duration from 1 to 4 consecutive days; the majority of SD events occur in April-May and July, with less during winter. The dust frequency presents large seasonal and intra-annual variation, with a maximum of 20 dust events in 2002 and a minimum of 7 in 2003. The use of TOMS-AI seems to be adequate for the characterization of dust over Athens despite the fact that 35% of the dusty days do not correspond to high AI values. The dust events are more intense during spring, mostly associated with dust transport from near surface to mid troposphere (vertical transport mechanism), while dust events detected only within the boundary layer have the lowest AOD values. On the other hand, the dust events in summer are of larger duration due to stable weather conditions and absence of precipitation and transportation at elevated heights. © 2012 Taylor and Francis Group, LLC.

Renal impairment (RI) is a common complication affecting patients with multiple myeloma (MM). Timely identification of MM-related RI and early treatment with novel antimyeloma agents can reverse renal damage in a high proportion of patients and improve outcomes. The IMiDs® immunomodulatory compound lenalidomide (Len) in combination with dexamethasone (Dex) is an effective and well-tolerated regimen for patients with relapsed or refractory (RR) MM. A retrospective analysis of Phase III data has shown that Len/Dex remains effective and well-tolerated in patients with moderate or severe RI, albeit with an increase in myelosuppression. This analysis demonstrated that in a high proportion of patients Len/Dex treatment can reverse MM-related RI and restore normal function. Lenalidomide has a predominantly renal route of excretion and in patients with RI the plasma concentration and half-life of the drug are significantly increased. As a consequence, lower starting doses are required in patients with RI to avoid over-exposure and an increased risk of adverse events, while maintaining good therapeutic index. A prospective cohort study in 50 patients with RRMM has reported that when Len/Dex dosing was adjusted according to renal function, response rates and survival outcomes were similar in patients with and without RI, and there was no increase in adverse events in patients with RI. Further clinical studies are required to confirm the efficacy and tolerability of Len/Dex regimens in MM patients with RI, and to evaluate the impact of reversing renal damage in terms of patient survival. © 2012 Elsevier Ltd.

The modulation of spontaneous light emission of active centers through elastic waves in Si/SiO2 multilayer phoxonic structures that support dual photonic-phononic localized modes, in the bulk or at the surface, is studied by means of rigorous full electrodynamic and elastodynamic calculations. Our results show that strong dynamic modulation of the spontaneous emission can be achieved through an enhanced acousto-optic interaction when light and elastic energy are simultaneously localized in the same region.

In this paper we propose the design and implementationof a Turing Test (TT) for the research of the singingvoice. Although the TT is mainly related to the researchfield of Artificial Intelligence (AI), being used both as acriterion and an operational guide by the scientists of thisfield, with the present paper we attempt to introduce arather different approach to the TT. Given the fact ofvarious disputes over the validity of the TT as a criterionof AI, one might argue that the TT is nothing more thana ‘philosophical fossil’, a left-over and remainder of pastand outdated philosophical assumptions about the natureof human intelligence. The problem of an unavoidablesubjectivity in the results of TT experiments hasstrengthen the question about the usefulness of the TT asa research means. Our goal is to introduce a new scopefor the use of the TT not as a criterion of intelligence butas an ‘instrument’ for tracing certain features of humanjudgment in various fields. Pretty much in the fashion ofa Transcendental philosophical stance, we face the TT asa procedure in which what is judged is judgement itself.Specifically, in the present paper we attempt to exhibitthe way in which a TT can be used to trace and highlightfeatures of human judgment regarding the singing voice.Are certain factors like culture, gender, age or familiaritywith music technology basic parameters of the way inwhich humans perceive and judge artificial and naturalsinging voice? Is the TT a worn off chapter in the historyof the philosophy of AI or could it be a brand new toolfor the research in fields like psychoacoustics, cognitivemusicology, social psychology of music and generallyfor the research on research itself?1 This is the kind ofquestions that we intend to raise concerning the future ofthe TT, starting with a paper for a possible ‘singingvoice TT’.

Our present contribution is a resume of a series of our studies by which we make an effort to explore the factors that are related to the acceptance of evolutionary theory among Greek and other variouscountries perspective and active educators using the conceptual ecology for biological evolution as a theoretical lens. Our central question refers to the role of the type of religiosity of a certain population in making their willingness for acceptance or rejection of evolution in the school environment. The Theory of Evolution (ET) is considered as concept - threshold that needs to be passed before someone can develop his/her understanding (Kinchin 2010) of a broader perspective of natural phenomena and of the nature of science. Most educational research has shown that the result of the teaching of ET is not positive in different parts of the world. Moreover research shows that the acceptance of the ET is restricted and the knowledge is limited and controversial among school science students and teachers. Large percentages of science teachers—close to a majority in many samples—reject ET and support the teaching of antievolutionary ideas in schools (Nehm & Schonfeld, 2007). Thus evolution remains a problematic subject for many science teachers. We make the hypothesis that the type of qualitative characteristics of the religion a nation or population group holds, is an essential factor in determining the level of acceptance of evolution, and their readiness to make changes in their believes, as well. More specifically, we advocate that the student and teacher populations that come from countries with a Greek-Orthodox background are m​

Synoptic climatology relates the atmospheric circulation with the surface environment. The aim of this study is to examine the variability of the surface meteorological patterns, which are developing under different synoptic scale categories over a suburban area with complex topography. Multivariate Data Analysis techniques were performed to a data set with surface meteorological elements. Three principal components related to the thermodynamic status of the surface environment and the two components of the wind speed were found. The variability of the surface flows was related with atmospheric circulation categories by applying Correspondence Analysis. Similar surface thermodynamic fields develop under cyclonic categories, which are contrasted with the anti-cyclonic category. A strong, steady wind flow characterized by high shear values develops under the cyclonic Closed Low and the anticyclonic H-L categories, in contrast to the variable weak flow under the anticyclonic Open Anticyclone category. © 2012 Springer-Verlag.

Pollen assemblages recovered from a 5 m sediment core from the Vravron coastal marsh suggest a close correlation between vegetation development and human presence in Attica, and provide the first complete record of middle to late Holocene vegetation history. Correlation of pollen with archaeological data attempts to decode the man–environment relations of the past, within the context of the known climatic variability of the mid late Holocene, in the vicinity of ancient Athens, an area of high historical significance. The pollen record of Vravron denotes a rather variable landscape where open Mediterranean evergreen pine woods alternated with maquis shrublands and grasslands, where human activities and climate have left their imprints on vegetation. During the last 5,000 years agricultural practices displayed several variations: cereal cultivation appears more intense during the Bronze Age, especially in the Mycenaean, while a spread of Olea is observed during Geometric to Classical times. The gradual abandonment of Olea cultivation evidenced in our pollen diagram came as a result of the displacement of human activities in the interior of Mesogaia in Hellenistic and Roman times. Olea and cereal cultivation intensification is observed again during the Mesobyzantine period. In the upper part of the core evidence of intense soil erosion and expansion of Vravron wetland was recorded, coinciding with the Little Ice Age climatic event and the introduction of Arvanites populations in the area.

Background:Vascular endothelial growth factor action in tumour angiogenesis is well characterised; nevertheless, it functions as a key element in the promotion of the immune systems evasion by tumours. We sought to investigate the possible direct effect of VEGF on T-cell activation and through which type of VEGF receptor it exerts this effect on cells isolated from ovarian cancer patients ascites.Methods:T cells isolated from the ascites of ovarian cancer patients were cultured with anti-CD3 and IL-2, with or without VEGF for 14 days and the number of viable T cells was counted. Cytotoxic activity of cultured T cells and expression of VEGF receptor-2 (VEGFR-2), was assayed.Results:The addition of VEGF in cultures significantly reduced the number and proliferation rate of T cells in a dose-dependent manner and CD3 T cells expressed VEGFR-2 on their surface upon activation. Experiments with specific anti-VEGFR-2 antibodies revealed that the direct suppressive effect of VEGF on T-cell proliferation is mediated by VEGFR-2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells.Conclusion:Our study showed that ascites-derived T cells secrete VEGF and express VEGFR-2 upon activation. Vascular endothelial growth factor directly suppresses T-cell activation via VEGFR-2. © 2012 Cancer Research UK.

The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis is well characterized; nevertheless, it is also a key element in promoting tumor evasion of the immune system by downregulating dendritic cell maturation and thus T cell activation. We sought to investigate the possible direct effect of VEGF on T cell activation and through which type of VEGF receptor (VEGFR) it exerts this effect. Circulating T cells from healthy donors and ovarian cancer patients were expanded in cultures with anti-CD3 and IL-2 with or without VEGF for 14 days, and the number of T cells was assessed. Cultured T cells were also tested for their cytotoxic activity in a standard 4-hr 51Cr-release assay, and the expression of VEGFRs 1, 2 and 3 was assayed by flow cytometry, immunocytochemistry and Western blotting. To assess the ability of activated T cells to secrete VEGF, levels in culture supernatants were measured by enzyme linked immunosorbent assay. The addition of VEGF in cultures significantly reduced T cell proliferation in a dose-dependent manner. Protein expression studies demonstrated that CD3 + T cells express VEGFR-2 on their surface upon activation. Experiments with anti-VEGFR-2 antibodies showed that the direct suppressive effect of VEGF on T cell proliferation is mediated by VEGFR-2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells and that activated T cells secrete VEGF in the culture environment. Overall, our study shows that T cells secret VEGF and expresses VEGFR-2 upon activation. VEGF directly suppresses T cell activation via VEGF receptor type 2. © 2011 UICC.

Context. It is well established that some YSO jets (e.g. RW Aur) display different propagation speeds between their blue and red shifted parts, a feature possibly associated with the central engine or the environment in which the jet propagates. Aims: To understand the origin of asymmetric YSO jet velocities, we investigate the efficiency of two candidate mechanisms, one based on the intrinsic properties of the system and the other on the role of the external medium. In particular, a parallel or anti-parallel configuration between the protostellar magnetosphere and the disk magnetic field is considered, and the resulting dynamics examined both in an ideal and in a resistive magneto-hydrodynamical (MHD) regime. Moreover, we explore the effects of a potential difference in the pressure of the environment, as a consequence of the nonuniform density distribution of molecular clouds. Methods: Ideal and resistive axisymmetric numerical simulations were carried out for a variety of models, all of which are based on a combination of two analytical solutions, a disk wind and a stellar outflow. The initial two-component jet is modified by either inverting the orientation of its inner magnetic field or imposing a constant surrounding pressure. The velocity profiles are studied by assuming steady flows as well as after strong time variable ejection is incorporated. Results: Discrepancies between the speeds of the two outflows in opposite directions can indeed occur both due to unaligned magnetic fields and different outer pressures. In the former case, the asymmetry appears only on the dependence of the velocity on the cylindrical distance, but the implied observed value is significantly altered when the density distribution is also taken into account. On the other hand, a nonuniform medium collimates the two jets unevenly, directly affecting their propagation speed. A further interesting feature of the pressure-confined outflow simulations is the formation of static knots whose spacing seems to be associated with the ambient pressure. Conclusions: Jet velocity asymmetries are anticipated both when multipolar magnetic moments are present in the star-disk system and when nonuniform environments are considered. The latter is an external mechanism that can easily explain the large timescale of the phenomenon, whereas the former naturally relates it to the YSO intrinsic properties.

An attempt is made to explore the vertical structure of the surface explosive cyclones in the Mediterranean on a climatological basis during the cold period of the year in order to get a better insight in the interaction between the upper and lower levels responsible for the genesis and evolvement of the phenomenon. The vertical profile of the explosive cyclones was examined with the aid of the vertical tracing software of the University of Melbourne Cyclone Tracking Algorithm, using the 1 × 1° spatial resolution of ERA-40 reanalysis data. It was found that about 57 % of the track steps of surface explosive cyclones extend up to 500 hPa. The north-westward tilting of the surface cyclones with height during the stage of explosive cyclogenesis, with a mean distance of 350 km between mean sea and 500 hPa levels, confirms the importance of baroclinicity. About 45 % of the surface explosive cyclones reached their maximum depth before their 500 hPa counterparts, implying the role of surface processes. © 2012 Springer-Verlag.

Composite TiO 2 photocatalytic ultrafiltration (UF) membranes were developed through chemical vapour layer-by-layer deposition (LBL/CVD) of TiO 2. The technique comprised chemisorption or physisorption of the titanium isopropoxide (TTIP) vapour and a subsequent oxidative treatment in order to promote the precursor condensation and generate new adsorption sites for the accomplishment of the successive adsorption/surface reaction steps. Both membrane sides were covered with TiO 2 photocatalyst without affecting the high water recovery efficiency. For reasons of comparison, one of the membranes was prepared through TiO 2 nanoparticle growth (NPG/CVD), a procedure extensively studied in a previous work of our group. The membrane efficiency in photo degradation of methyl orange was evaluated in an innovative continuous flow reactor, applying UV irradiation on the annular and bore surfaces. The membranes developed through the physisorption path were highly efficient in the decomposition of azo-dye pollutant, exhibiting low adsorption-fouling tendency and high water permeability. © 2011 Elsevier B.V.

Aim: The purpose of this study was to compare two single agents paclitaxel (intravenous) versus vinorelbine (oral) in non-small cell lung cancer (NSCLC) patients with performance status (PS):2. Patients and Methods: The patients were randomized to receive either oral vinorelbine 60 mg/m 2 on days I, 8, 15 every 4 weeks for 4 cycles (group A) or paclitaxel 90 mg/m 2 intravenously for 1 h on days 1, 8, 15 every 4 weeks for a total of 4 cycles (group B). Results: Among the 74 eligible patients (36 in arm A and 38 in arm B) in arm A, two (6%) had a partial response (95% Cl, 0.7-18.7) and 5 (14%) had stable disease (95% CI, 4.7-29.5). In arm B, five (13%) had a partial response (95% CI, 4.4-28.1) and 7 (18%) had stable disease (95% CI, 7.7-34.3). No significant difference was found in terms of clinical benefit between the two groups after two cycles of treatment except for appetite in favour of paclitaxel (p=0.01). Median survival was 3.1 months (95% CI, 2.2-4.0) for arm A and 5.1 months (95% CI, 2.7-7.6) for arm B (p=0.95). Toxicity was mild and only alopecia was more profound in the patients of arm B (p=0.008). Conclusion: No significant difference was found in clinical benefit between PS:2 NSCLC patients treated with either vinorelbine or paclitaxel.

We present a catalog of photometric and spectroscopic data collected during and around of EE Cep eclipses in 1997, 2003 and 2008/9. The photometric data were obtained with 25 different instruments, mainly in Johnson-Cousins UBV(RI)C bands, and some small sets of the data were obtained with narrow interference filters, placed on, or around of H-alpha and H-beta lines. The photometry from the last two eclipses have been compiled into the set of consistent photometric data in UBV(RI)C bands, that has been used in the paper to modelling of the eclipses in EE Cep system. The 100 of spectra released in this catalog were obtained with 8 of different spectrographs at low, medium and high resolutions (R in range ~2000-48000). About half of them (54 spectra) cover narrow ranges of order 200 Angstroms with H-alpha, H-beta lines or NaI dublet, and the second part (46 spectra) cover longer ranges of wavelengths - several thousands of Angstroms in the visual domain or in the near infrared. (7 data files).

This study is based on observations obtained with the 1.3-m Warsaw telescope at the Las Campanas Observatory, Chile, during the OGLE-II and OGLE-III projects, between 1997 and 2008. (4 data files).

X-ray mosaic images from combined EPIC pn and MOS data of the SMC region centred at RA=01:00:30, DE=-72:28:00 (J2000). The three images were produced in the three energy bands 0.2-1.0keV, 1.0-2.0keV, and 2.0-4.5keV. The images are exposure-corrected and for EPIC pn out-of-time event subtracted, but not detector-background subtracted and not vignetting-corrected. (4 data files).

The serum levels of several angiogenic cytokines are increased in patients withWaldenström macroglobulinemia (WM). Angiopoietin-2 is also increased and the balance of angiopoietin-1/angiopoietin-2, which antagonize for the receptor tyrosine kinase Tie-2 is in favor of angiopoietin-2. Lymphoplasmacytic cells may produce VEGF, but they also produce large amounts of CCL-3 which attracts macrophages, and probably mast cells. Mast cells support lymphoplasmacytic cells and may also produce VEGF. VWF is stored in the Weibel-Palade bodies together with several other mediators, including angiopoietin-2. The endothelial cells (ECs) release the content of Weibel-Palade bodies in response to stimuli, such as VEGF and VWF and other molecules (such as angiopoitein-2) are released simultaneously. VWF may also have an inhibitory activity in the constitutive VEGFR-2-dependent pathway(s), which promote EC migration.