Publications by Type: Journal Article

Marine and terrestrial biological and biogeochemical proxies in three sediment cores from North and SE Aegean and northern Levantine Seas record continuous warm and humid conditions between 5.5 and 4.0 ka BP related to the establishment of relatively stratified conditions in the upper water column. These conditions may have resulted from the concordant albeit weak Mid-Holocene South Asian monsoon forcing, combined with lighter Etesian winds. During this interval, sea surface temperatures fluctuate in the Aegean Sea, although exhibiting a strong positive shift at*4.8 ka BP. The warm and humid climatic conditions triggered upper water column stratification and enhancement of the deep chlorophyll maximum (DCM), leading to dysoxic conditions and the deposition of a sapropel-like layer, but only in the SE Aegean site. In contrast to the shallow water SE Aegean, the deeper North Aegean and the northern Levantine sites, although experiencing stratification in the upper parts of the water column, did not achieve bottom-water dysoxia. Thus, a top–bottom mechanism of stratification–DCM development accompanied by fast transport and burial of organic matter is a likely explanation for the preservation of productivity signal in the shallow sites of the SE Aegean and establishment of sapropelic conditions during the warm and humid Mid-Holocene. The termination of the Mid-Holocene warm and humid phase coincides with the ‘‘4.2 ka’’ climate event. Our data exhibit an N–S time transgressive aridification gradient around the Aegean Sea, most probably associated with the reorganization of the general atmospheric circulation during the Mid-Holocene.

Marine and terrestrial biological and biogeochemical proxies in three sediment cores from North and SE Aegean and northern Levantine Seas record continuous warm and humid conditions between 5.5 and 4.0 ka BP related to the establishment of relatively stratified conditions in the upper water column. These conditions may have resulted from the concordant albeit weak Mid-Holocene South Asian monsoon forcing, combined with lighter Etesian winds. During this interval, sea surface temperatures fluctuate in the Aegean Sea, although exhibiting a strong positive shift at*4.8 ka BP. The warm and humid climatic conditions triggered upper water column stratification and enhancement of the deep chlorophyll maximum (DCM), leading to dysoxic conditions and the deposition of a sapropel-like layer, but only in the SE Aegean site. In contrast to the shallow water SE Aegean, the deeper North Aegean and the northern Levantine sites, although experiencing stratification in the upper parts of the water column, did not achieve bottom-water dysoxia. Thus, a top–bottom mechanism of stratification–DCM development accompanied by fast transport and burial of organic matter is a likely explanation for the preservation of productivity signal in the shallow sites of the SE Aegean and establishment of sapropelic conditions during the warm and humid Mid-Holocene. The termination of the Mid-Holocene warm and humid phase coincides with the ‘‘4.2 ka’’ climate event. Our data exhibit an N–S time transgressive aridification gradient around the Aegean Sea, most probably associated with the reorganization of the general atmospheric circulation during the Mid-Holocene.

An underwater geomorphological survey along the coasts of six Cycladic islands (Sifnos, Antiparos, Paros, Naxos, Iraklia and Keros) revealed widespread evidence of seven submerged tidal notches. At least seven former shorelines were identified at depths between 280 ± 20 and 30 ± 5 cm below modern sea level. The vertical succession of several submerged notches suggests the occurrence of rapid subsidence events, potentially of seismic origin. Comparison with other sea-level indicators from Naxos and Delos islands indicates that these relative sea-level changes took place after 3300 BP and provides a rough estimate of the time of development of several submerged shorelines. The submergence of the uppermost notch at −30 ± 5 cm is ascribed to effects of the recent global sea-level rise occurred during the last two centuries and, at least in part, to effects of recent earthquakes. Potential effects of the 1956 Amorgos earthquake with regard to coseismic and post-seismic vertical displacement have been recently investigated using a modellistic approach. According to the above, the lower shorelines should result from repetitive subsidence events and not from gradual subsidence.

We report on the increase of up to 37.5% in conversion efficiency of a Si-based solar cell after deposition of light-emitting Cd-free, CuInS 2/ZnS core shell quantum dots on the active area of the cell due to the combined effect of down-conversion and the anti- reflecting property of the dots. We clearly distinguished the effect of down-conversion from anti-reflection and estimated an enhancement of up to 10.5% in the conversion efficiency due to down-conversion. © 2014 AIP Publishing LLC.

In this report, a panel of European myeloma experts discuss the role of pomalidomide in the treatment of relapsed and refractory multiple myeloma (RRMM). Based on the available evidence, the combination of pomalidomide and low-dose dexamethasone is a well-tolerated and effective treatment option for patients with RRMM who have exhausted treatment with lenalidomide and bortezomib. The optimal starting dose of pomalidomide is 4 mg given on days 1-21 of each 28-day cycle, whereas dexamethasone is administered at a dose of 40 mg weekly (reduced to 20 mg for patients aged >75 years). The treatment should continue until evidence of disease progression or unacceptable toxicity. Dose-modification schemes have been established for patients who develop neutropenia, thrombocytopaenia and other grade 3-4 adverse events during pomalidomide therapy. Guidance on the prevention and management of infections and venous thromboembolism is provided, based on the available clinical evidence and the experience of panel members. The use of pomalidomide in special populations, such as patients with advanced age, renal impairment or unfavourable cytogenetic features, is also discussed. © 2014 Macmillan Publishers Limited. All rights reserved.

Olive oil is an important lipid source of the Mediterranean diet which has been associated with lower incidence of cardiovascular diseases whereas olive pomace (OP), a natural by-product of olive oil production, has been found to contain micro constituents with antioxidant, antithrombotic and antiatherogenic activities. The evaluation of OP in order to produce sustainable functional food and neutraceuticals has been the subject of research over the last years. All recent data, focusing on the anti-inflammatory properties of olive oil derived from olive (Olea europaea) and OP along with the potential production of sustainable functional food and neutraceuticals, are presented in this review.

The Health Information Technology can improve public health, quality of health care etc. Thus, it is important for professionals to be well educated by training programs. The aim of this paper is to record all the educational programs with specializations in Health Informatics, Medical Informatics, Bioinformatics, Biomedical Informatics and Biomedical Engineering in European Universities and Institutions. An on-line research was conducted on Scopus, PubMed, Scholar Google, and Google. More than 150 universities and colleges in Europe conduct educational programs for these domains. The majority them, expertise in Biomedical Engineering (31%), 22% of the educational programs correspond to Bioinformatics, while Health Informatics studies have 18%. On the last few years, a growth of Health informatics professionals has been observed in Europe.

This study focuses on analyzing the extreme aerosol loading and the mechanisms, source areas and meteorological conditions that favored the abnormal dust exposure towards Arabian Sea during June 2008. The analysis reveals that the spatial-averaged aerosol optical depth (AOD) over Arabian Sea in June 2008 is 0.5 (78.2%) higher than the 2000-2013 mean June value and is mostly attributed to the enhanced dust activity and several (18) dust storms originated from the Sistan region (Iran-Afghanistan borders). Landsat images show that the marshy lakes in Sistan basin got dried during the second half of June 2008 and the alluvial silt and saline material got easily eroded by the intense Levar winds, which were stronger (>15-20ms-1) than the climatological mean for the month of June. These conditions led to enhanced dust exposure from Sistan that strongly affected the northern and central parts of the Arabian Sea, as forward air-mass trajectories show. The NCEP/NCAR reanalysis reveals an abnormal intensification and spatial expansion of the Indian low pressure system towards northern Arabian Sea in June 2008. This suggests strengthening of the convection over the arid southwest Asia and exposure of significant amount of dust, which can reach further south over Arabian Sea favored by the enhanced cyclonic circulation. MODIS imagery highlighted several dust storms originated from Sistan and affecting Arabian Sea during June 2008, while the SPRINTARS model simulations of increased AOD and dust concentration over Sistan and downwind areas are in agreement with ground-based and satellite observations. © 2014 Elsevier Ltd.

Glycosaminoglycans (GAGs) due to their hydrophilic character and high anionic charge densities play important roles in various (patho)physiological processes. The identification and quantification of GAGs in biological samples and tissues could be useful prognostic and diagnostic tools in pathological conditions. Despite the noteworthy progress in the development of sensitive and accurate methodologies for the determination of GAGs, there is a significant lack in methodologies regarding sample preparation and reliable fast analysis methods enabling the simultaneous analysis of several biological samples. In this report, developed protocols for the isolation of GAGs in biological samples were applied to analyze various sulfated chondroitin sulfate- and hyaluronan-derived disaccharides using fluorophore-assisted carbohydrate electrophoresis (FACE). Applications to biologic samples of clinical importance include blood serum, lens capsule tissue and urine. The sample preparation protocol followed by FACE analysis allows quantification with an optimal linearity over the concentration range 1.0-220.0 microg/mL, affording a limit of quantitation of 50 ng of disaccharides. Validation of FACE results was performed by capillary electrophoresis and high performance liquid chromatography techniques.

In the MM-015 trial, melphalan-prednisone-lenalidomide followed by lenalidomide maintenance (MPR-R) significantly prolonged progression-free survival versus melphalan-prednisone (MP) in newly diagnosed patients with multiple myeloma aged ≥ 65 years. Health-related quality of life (HRQoL), a secondary endpoint of MM-015, was also improved with MPR-R. This sub-analysis evaluated the impact of individual predictive factors on HRQoL. Patients completed HRQoL questionnaires at baseline, every third cycle and at progressive disease (PD)/treatment discontinuation. In a mixed-effects model female gender, advanced age and PD negatively affected HRQoL while better treatment responses showed positive effects. Compared to PD, HRQoL during MPR-R treatment was statistically significantly better in two of six preselected domains both of which were also clinically meaningful. HRQoL scores at end of treatment were all either improved or not statistically significantly different versus baseline. In conclusion, continuous treatment with MPR-R, which delays PD, appears to be associated with clinically meaningful improvements in HRQoL. © 2014 Informa UK, Ltd.

Postoperative fast-track recovery protocols combine various methods to support immediate care of patients who undergo major surgery. These protocols include control of postoperative pain and early beginning of oral diet and mobilization. The combination of these approaches may reduce the rate of postoperative complications and facilitate hospital discharge. The aim of this study was to evaluate progress and parameters of fast-track recovery after major liver and pancreatic resection. A descriptive bibliographical review from 2001 to 2012 via electronic databases such as MEDLINE, PubMed, and Google Scholar was undertaken. Articles that focused on a fast-track protocol were studied. Reports focusing on the implementation of a fast-track protocol in the postoperative recovery of patients after major hepatectomy or pancreatectomy were selected. Fast-track protocols may be applicable to patients recovering after major liver or pancreatic resection. Future research should be focused on particular parameters of the fast-track protocol separately.

Zymomonas mobilis subsp. mobilis is one of the most rigorous ethanol-producing organisms known to date, considered by many to be the prokaryotic alternative to yeast. The two most applied Z. mobilis subsp. mobilis strains, ZM4 and CP4, derive from Recife, Brazil, and have been isolated from sugarcane fermentations. Of these, ZM4 was the first Z. mobilis representative strain to be sequenced and analyzed. Here, we report the finishing of the genome sequence of strain CP4, which is highly similar but not identical to that of ZM4.

BACKGROUND: Occurrence, elicitors and treatment of severe allergic reactions are recognized and reported differently between countries. We aimed to collect standardized data throughout Europe on anaphylaxis referred for diagnosis and counselling. METHODS: Tertiary allergy, dermatology and paediatric units in 10 European countries took part in this pilot phase of the first European Anaphylaxis Registry, from June 2011 to March 2014. An online questionnaire was used to collect data on severe allergic reactions based on the medical history and diagnostics. RESULTS: Fifty-nine centres reported 3333 cases of anaphylaxis, with 26.7% below 18 years of age. Allergic reactions were mainly caused by food (children and adults 64.9% and 20.2%, respectively) and insect venom (20.2% and 48.2%) and less often by drugs (4.8% and 22.4%). Most reactions occurred within 30 min of exposure (80.5%); a delay of 4+ hours was mainly seen in drug anaphylaxis (6.7%). Symptom patterns differed by elicitor, with the skin being affected most often (84.1%). A previous, usually milder reaction to the same allergen was reported by 34.2%. The mainstay of first-line treatment by professionals included corticoids (60.4%) and antihistamines (52.8%). Only 13.7% of lay- or self-treated reactions to food and 27.6% of insect anaphylaxis received on-site adrenaline. CONCLUSION: This pilot phase of a pan-European registry for severe allergic reactions provides for the first time data on anaphylaxis throughout Europe, demonstrates its potential functionality and allows a comparison of symptom patterns, elicitors and treatment habits between referral centres and countries.

BACKGROUND: Many neuropsychiatric disorders, including stress-related mood disorders, are complex multi-parametric syndromes. Susceptibility to stress and depression is individually different. The best animal model of individual differences that can be used to study the neurobiology of affect regards spontaneous reactions to novelty. Experimentally, when naive rats are exposed to the stress of a novel environment, they display a highly variable exploratory activity and are classified as high or low responders (HR or LR, respectively). Importantly, HR and LR rats do not seem to exhibit a substantial differentiation in relation to their 'depressive-like' status in the forced swim test (FST), a widely used animal model of 'behavioral despair'. In the present study, we investigated whether FST exposure would be accompanied by phenotype-dependent differences in hippocampal gene expression in HR and LR rats. RESULTS: HR and LR rats present a distinct behavioral pattern in the pre-test session but develop comparable depressive-like status in the second FST session. At 24 h following the second FST session, HR and LR rats (stressed and unstressed controls) were sacrificed and hippocampal samples were independently analyzed on whole rat genome Illumina arrays. Functional analysis into pathways and networks was performed using Ingenuity Pathway Analysis (IPA) software. Notably, hippocampal gene expression signatures between HR and LR rats were markedly divergent, despite their comparable depressive-like status in the FST. These molecular differences are reflected in both the extent of transcriptional remodeling (number of significantly changed genes) and the types of molecular pathways affected following FST exposure. A markedly higher number of genes (i.e., 2.28-fold) were statistically significantly changed following FST in LR rats, as compared to their HR counterparts. Notably, genes associated with neurogenesis and synaptic plasticity were induced in the hippocampus of LR rats in response to FST, whereas in HR rats, FST induced pathways directly or indirectly associated with induction of apoptotic mechanisms. CONCLUSIONS: The markedly divergent gene expression signatures exposed herein support the notion that the hippocampus of HR and LR rats undergoes distinct transcriptional remodeling in response to the same stress regimen, thus yielding a different FST-related 'endophenotype', despite the seemingly similar depressive-like phenotype.

New geomorphological investigations along the coasts of Corfu, Othonoi, Paxoi, and Antipaxoi Islands allowed the identification of recent fossil shorelines.Former sea-level positions were deduced from sea-level indicators. A ‘modern’ tidal notch, submerged c. −20 cm, was observed in all studied islands.This notch is regarded to have been submerged by the global sea-level rise that occurred during the 19th and 20th centuries at a rate exceeding thepossibilities of intertidal bioerosion. Its presence provides evidence that no vertical tectonic movements occurred since its formation. On Corfu, impactsof ancient earthquakes have left some marks of emergence at about ≥ +130 ± 11, +110 ± 11, +65 ± 11, +40 ± 11, and +25 ± 11 cm, as well as marks ofsubmergence at about −40 to −50, −85 ± 11, −120 ± 11, and −180 ± 11 cm. The emergence of +130 ± 11 cm, previously dated at about 790–400 cal. BC, was detected through erosion notches at various sites in the western part of Corfu and appears to continue even more west, at Othonoi Island. Tidalnotches submerged at depths exceeding 0.4 m were observed in the northeastern part of the island and suggest the local occurrence of a sequence offour coseismic subsidences, with average vertical displacements of 40 cm, during at least the last few millennia. At Paxoi and Antipaxoi, Holocene verticalmovements seem to have been mainly of subsidence. At Paxoi, the ‘modern’ notch was found at about −20 to −30 cm, while four more submerged tidalnotches were distinguished at about −40 ± 11, −60 ± 11, −75 ± 11, and −90 ± 11 cm, while in Antipaxoi, three submerged tidal notches were distinguishedat about −60 ± 11, −75 ± 11, and −120 ± 11 cm.

This article proposes an analysis of the historical changes in the aspectual system of Greek as a process of grammaticalization and subjectification, thus challenging the traditional view of Greek verbal aspect as a stable and in fact extremely conservative category, possibly very close to that of Proto-Indo- European. Specifically, the claim put forward here is that the original tripartite morphological opposition (Aorist – Present – Perfect stems) expressed Aktionsart, i.e. lexical aspect, distinctions (punctuality/telicity– durativity/atelicity–state, respectively) while the modern binary morpho- logical opposition (Aorist–Present stems) expresses the purely aspectual perfective–imperfective opposition. Since Aktionsart is based on inherent features of the action/state denoted by the verb while aspect expresses the speaker’s point of view, this constitutes a shift from objectivity to subjectivity as well as a somewhat atypical grammaticalization process. Keywords: gradient; perfective; progressive; habitual; perfect 

Context. Chemically inhomogeneous populations are observed in most globular clusters, but not in open clusters. Cluster mass seems to play a key role in the existence of multiple populations. Aims: Studying the chemical homogeneity of the most massive open clusters is needed to better understand the mechanism of their formation and determine the mass limit under which clusters cannot host multiple populations. Here we studied NGC 6705, which is a young and massive open cluster located towards the inner region of the Milky Way. This cluster is located inside the solar circle. This makes it an important tracer of the inner disk abundance gradient. Methods: This study makes use of BVI and ri photometry and comparisons with theoretical isochrones to derive the age of NGC 6705. We study the density profile of the cluster and the mass function to infer the cluster mass. Based on abundances of the chemical elements distributed in the first internal data release of the Gaia-ESO Survey, we study elemental ratios and the chemical homogeneity of the red clump stars. Radial velocities enable us to study the rotation and internal kinematics of the cluster. Results: The estimated ages range from 250 to 316 Myr, depending on the adopted stellar model. Luminosity profiles and mass functions show strong signs of mass segregation. We derive the mass of the cluster from its luminosity function and from the kinematics, finding values between 3700 M⊙ and 11 000 M⊙. After selecting the cluster members from their radial velocities, we obtain a metallicity of [Fe/H] = 0.10 ± 0.06 based on 21 candidate members. Moreover, NGC 6705 shows no sign of the typical correlations or anti-correlations between Al, Mg, Si, and Na, which are expected in multiple populations. This is consistent with our cluster mass estimate, which is lower than the required mass limit proposed in the literature to develop multiple populations. Based on the data obtained at ESO telescopes under programme 188.B-3002 (the public Gaia-ESO spectroscopic survey, PIs Gilmore and Randich) and on the archive data of the programme 083.D-0671.Full Table 2 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/569/A17

Introduction Generic products of antiepileptic drugs (AEDs) are currently a controversial topic as neurologists and patients are reluctant to switch from brand products to generics and to switch between generics. Objective The aim of this study was to provide enlightenment on issues of bioequivalence (BE) and interchangeability of AED products. Methods Monte Carlo simulations of the classic 2 x 2 BE studies were performed to study the effect of sample size, within-subject variability, and the true difference in pharmacokinetic values of the products under comparison on BE acceptance of generic AED products. Simulations were extended to study the comparative performance of two generic AED products against the same innovative product. The simulated results are compared with literature data on AEDs. Results The question with regard to bioavailability (BA) is whether two formulations are different, while for BE the question is whether two formulations are sufficiently similar in terms of extent and rate of absorption. Therefore, the criteria for BA and BE and the statistical analysis involved in their analysis are different. Two generic formulations that meet regulatory approval requirements for generics by being bioequivalent to the same innovative AED may not be bioequivalent to one another and therefore should not be regarded as equal or as therapeutically equivalent products. A switch from a standard or an immediate-release formulation to a modified-release product, which comprises extended-release or delayed-release formulations, should not be regarded as a switch between generics, but rather as a switch between different formulation types. Discussions Switches between bioequivalent generic AED products could potentially lead to larger changes in plasma levels and exposure than the brand-to-generic switch. The simulation work verified the clinical findings that not all generic AED products bioequivalent to the same innovative product are bioequivalent to one another. Conclusions Two generic formulations that meet regulatory approval requirements for generics, by being bioequivalent to the innovative AED, may not be bioequivalent to one another. Additional BE criteria are needed for a formulation switch, particularly in epilepsy, where a breakthrough seizure may change a patient's status from seizure-free to refractory.

Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10-8) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10-4] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10-9) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 × 10-69). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.

Hypersensitivity diseases are not adequately coded in the International Coding of Diseases (ICD)-10 resulting in misclassification, leading to low visibility of these conditions and general accuracy of official statistics. To call attention to the inadequacy of the ICD-10 in relation to allergic and hypersensitivity diseases and to contribute to improvements to be made in the forthcoming revision of ICD, a web-based global survey of healthcare professionals' attitudes toward allergic disorders classification was proposed to the members of European Academy of Allergy and Clinical Immunology (EAACI) (individuals) and World Allergy Organization (WAO) (representative responding on behalf of the national society), launched via internet and circulated for 6 week. As a result, we had 612 members of 144 countries from all six World Health Organization (WHO) global regions who answered the survey. ICD-10 is the most used classification worldwide, but it was not considered appropriate in clinical practice by the majority of participants. The majority indicated the EAACI-WAO classification as being easier and more accurate in the daily practice. They saw the need for a diagnostic system useful for nonallergists and endorsed the possibility of a global, cross-culturally applicable classification system of allergic disorders. This first and most broadly international survey ever conducted of health professionals' attitudes toward allergic disorders classification supports the need to update the current classifications of allergic diseases and can be useful to the WHO in improving the clinical utility of the classification and its global acceptability for the revised ICD-11.

OBJECTIVE: The aims of this study were to investigate gross motor development in Greek infants and establish AIMS percentile curves and to examine possible association of AIMS scores with socioeconomic parameters. METHODS: Mean AIMS scores of 1068 healthy Greek full-term infants were compared at monthly age level with the respective mean scores of the Canadian normative sample. In a subgroup of 345 study participants, parents provided, via interview, information about family socioeconomic status. Multiple linear regression analysis was performed to evaluate the relationship of infant motor development with socioeconomic parameters. RESULTS: Mean AIMS scores did not differ significantly between Greek and Canadian infants in any of the 19 monthly levels of age. In multiple linear regression analysis, the educational level of the mother and also whether the infant was being raised by grandparents/babysitter were significantly associated with gross motor development (p=0.02 and p<0.001, respectively), whereas there was no significant correlation of mean AIMS scores with gender, birth order, maternal age, paternal educational level and family monthly income. CONCLUSIONS: Gross motor development of healthy Greek full-term infants, assessed by AIMS during the first 19months of age, follows a similar course to that of the original Canadian sample. Specific socioeconomic factors are associated with the infants’ motor development.

Purpose: The establishment of high dependency units (HDUs) has been an undoubted advance in the management of patients undergoing major oncological procedures. The aim of this study was to examine the impact of various preoperative and perioperative patients' characteristics on the prolonged HDU stay. Methods: We conducted a retrospective study including all gynecologic oncology patients who underwent surgical management and were admitted postoperatively to our hospitals' HDU from 2006 to 2010. Results: A total of 1,014 patients were transferred to the HDU and divided into two groups according to the length of HDU stay. Group A consisted of 840 (82.8 %) patients who stayed in the HDU for ≤24 h and Group B included 174 (17.2 %) patients who remained in the HDU under close observation for >24 h. Older age was the only preoperative characteristic that remained significantly associated with HDU prolonged stay. In addition, three intraoperative factors such as use of invasive hemodynamic monitoring, bowel resection and estimated blood loss were proved to be independently associated with prolonged HDU stay. Conclusion: Certain characteristics could identify those patients who are more likely to benefit most from HDU admission. © 2014 Springer-Verlag.

We explore a one-zone hadronic model that may be able to reproduce γ-ray burst (GRB) prompt emission with a minimum of free parameters. Assuming only that GRBs are efficient high-energy proton accelerators and without the presence of an ab initio photon field, we investigate the conditions under which the system becomes supercritical, i.e. there is a fast, non-linear transfer of energy from protons to secondary particles initiated by the spontaneous quenching of proton-produced γ-rays. We first show analytically that the transition to supercriticality occurs whenever the proton injection compactness exceeds a critical value, which favours high proton injection luminosities and a wide range of bulk Lorentz factors. The properties of supercriticality are then studied with a time-dependent numerical code that solves concurrently the coupled equations of proton, photon, electron, neutron and neutrino distributions. For conditions that drive the system deep into the supercriticality, we find that the photon spectra obtain a Band-like shape due to Comptonization by cooled pairs and that the energy transfer efficiency from protons to γ-rays and neutrinos is high reaching ∼0.3. Although some questions concerning its full adaptability to the GRB prompt emission remain open, supercriticality is found to be a promising process in that regard.

We explore a one-zone hadronic model that may be able to reproduce γ-ray burst (GRB) prompt emission with a minimum of free parameters. Assuming only that GRBs are efficient high-energy proton accelerators and without the presence of an ab initio photon field, we investigate the conditions under which the system becomes supercritical, i.e. there is a fast, non-linear transfer of energy from protons to secondary particles initiated by the spontaneous quenching of proton-produced γ-rays. We first show analytically that the transition to supercriticality occurs whenever the proton injection compactness exceeds a critical value, which favours high proton injection luminosities and a wide range of bulk Lorentz factors. The properties of supercriticality are then studied with a time-dependent numerical code that solves concurrently the coupled equations of proton, photon, electron, neutron and neutrino distributions. For conditions that drive the system deep into the supercriticality, we find that the photon spectra obtain a Band-like shape due to Comptonization by cooled pairs and that the energy transfer efficiency from protons to γ-rays and neutrinos is high reaching ∼0.3. Although some questions concerning its full adaptability to the GRB prompt emission remain open, supercriticality is found to be a promising process in that regard.

The consequences of demographic ageing, demographic and social-economic changes, changes in the structure of family, in the shrinkage of Welfare state, influenced the lifestyle of the older people and their social relations. The institution of Open Care Centers for the Elderly (KAPI) was created in the context of these conditions. This cross-sectional study examined the lifestyle of the older people who are member of KAPI and their association with all HRQoL dimensions. The results of this research showed that the main reason for the participants to become members of the KAPI was entertainment and/or companionship (98.4%). Additionally subjects who suffered from a chronic disease had significantly lower scores on all HRQoL dimensions, while participants who were members in the activity groups of KAPI had significantly higher scores. The elderly within the KAPI have many opportunities to meet with other persons of their age, and develop various activities and interests.

OBJECTIVE: To examine the effects of caregiver and patient characteristics on caregivers' medical care use and cost. METHODS: One hundred forty-seven caregiver/patient dyads were followed annually for 6 years in three academic Alzheimer's disease centers in the United States. Logistic, negative binomial, and generalized linear mixed models were used to examine overall effects of caregiver/patient characteristics on caregivers' hospitalizations, doctor visits, outpatient tests and procedures, and prescription and over-the-counter medications. RESULTS: Patients' comorbid conditions and dependence were associated with increased health-care use and costs of caregivers. Increases in caregiver depressive symptoms are associated with increases in multiple domains of caregivers' health-care use and costs. DISCUSSION: Findings suggest expanding our focus on dementia patients to include family caregivers to obtain a fuller picture of effects of caregiving. Primary care providers should integrate caregivers' needs in health-care planning and delivery. Clinical interventions that treat patients and caregivers as a whole will likely achieve the greatest beneficial effects.

BACKGROUND: Food allergy can impair health-related quality of life (HRQL). Food Allergy Quality of Life Questionnaires (FAQLQs) have been developed and validated, including an adult form (FAQLQ-AF). HRQL has not, to date, been measured across different European countries using a uniform methodology. OBJECTIVE: To translate and validate the FAQLQ-AF for use in 8 European countries (Iceland, The Netherlands, Poland, France, Spain, Italy, Greece, and Sweden). METHODS: The English FAQLQ-AF was translated, back-translated, and compared for use in the 8 relevant European languages. Adults with a perceived food allergy were recruited from outpatient departments and through a community survey. Participants completed the FAQLQ-AF, the Food Allergy Independent Measure, and questions concerning participants' characteristics. Validity of the FAQLQ-AF was analyzed for use in the 8 countries. RESULTS: The FAQLQ-AF had strong construct validity (r > 0.59) and an excellent internal consistency (Cronbach α > 0.95) in all countries. Total FAQLQ-AF scores (range 3.2-5.0) were significantly different across participating countries. CONCLUSION: The FAQLQ-AF is a suitable and valid instrument for measuring HRQL in food-allergic adults in Iceland, The Netherlands, Poland, France, Spain, Italy, Greece, and Sweden. The impact of food allergy on HRQL seems to differ among adults from the 8 participating European countries.

Background: Accumulating epidemiological evidence from several populations supports the important role of the Mediterranean-type diet (MeDi) in reducing the risk for age-related diseases such as Alzheimer's disease (AD). However, the relevant literature is clearly deficient for most Mediterranean countries that more closely adhere to the originally described MeDi. Greece resides in the Mediterranean basin, and older generations traditionally adhere to a MeDi. Methods: We here present the design and the preliminary baseline characteristics of the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). The HELIAD is a population-based, multidisciplinary, collaborative study designed to estimate the prevalence and incidence of AD, other dementias, mild cognitive impairment, and other neuropsychiatric conditions of aging in the Greek population and to investigate associations between nutrition and cognitive dysfunction/age-related neuropsychiatric diseases in this Mediterranean population. The study also ascertains several demographic, medical, social, environmental, clinical, nutritional, and neuropsychological determinants and lifestyle activities. Results: In total, 1,050 participants of a random sample have already completed the initial evaluation. The subjects were, on average, 73.4 (SD = 6.0) years old, 60% of the sample were female, and most of the participants were poorly educated with an average of 5.41 (SD = 3.5) years of education. The performance on the neuropsychological tests was equivalent to the average scores of previous normative Greek samples. More than one third of the population under investigation was considered to be at high risk for malnutrition. Conclusions: The HELIAD may provide important data for expanding our knowledge regarding the prevalence, incidence, and risk factors of AD and several other neuropsychiatric diseases in the Mediterranean region. © 2014 S. Karger AG, Basel.

BACKGROUND: Wheat is one of the most common food allergen sources for children and adults. The aim of this study was to characterize new wheat allergens using an IgE discovery approach and to investigate their IgE epitopes. METHODS: A cDNA expression library representing the wheat transcriptome was constructed in phage lambda gt11 and screened with IgE antibodies from wheat food allergic patients. IgE-reactive cDNA clones coding for portions of high molecular weight (HMW) glutenin subunits were identified by sequence analysis of positive clones. IgE epitopes were characterized using recombinant fragments from the HMW Bx7 and synthetic peptides thereof for testing of allergic patients' sera and in basophil degranulation assays. RESULTS: We found that the major IgE-reactive areas of HMW glutenins are located in the repetitive regions of the protein and could show that two independent IgE-reactive fragments from HMW Bx7 contained repetitive IgE epitopes. CONCLUSIONS: Our results demonstrate that IgE antibodies from wheat food allergic patients can recognize repetitive epitopes in one of the important wheat food allergens. Recombinant HMW Bx7 may be included into the panel of allergens for component-resolved diagnosis of wheat food allergy.

Hyperbilirubinaemia with or without jaundice is one of the side effects of atazanavir boosted with low-dose ritonavir (ATV/rit) related to the drug plasma levels, as a result of its metabolism by UGT1A1 - uridine diphosphate-glucuronosyl transferase. Genotyping for UGT1A1*28 before initiation of antiretroviral therapy containing atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Our objective was to estimate the prevalence of the UGTA1A1*28 polymorphism in HIV-infected individuals in Greece and to determine its potential association with hyperbilirubinaemia in patients receiving ATV/rit. The prevalence of the UGTA1A1*28 variant was estimated in 79 HIV-infected patients prior to the administration of the first-line treatment. The UGTA1A1*28 variant was detected in 46 out of 79 individuals (58.2%). Antiretroviral therapy was administered to 64/79 patients (81%). Among them, 26/64 (40.6%) received ATV/rit. Of the ATV/rit-treated patients, 14 were found to be carriers of the UGT1A1*28 variant (54%), and maximum serum bilirubin levels were significantly higher in the carrier population (4.71 vs. 2.69 mg/dL, p = 0.026). In 50% of the population, maximum levels were recorded in the first month of follow-up. Although carriage of UGT1A1 is linked with the development of hyperbilirubinaemia, the implementation of a pharmacogenomic approach in clinical practice cannot yet be recommended as a standard of care.

Hyperbilirubinaemia with or without jaundice is one of the side effects of atazanavir boosted with low-dose ritonavir (ATV/rit) related to the drug plasma levels, as a result of its metabolism by UGT1A1 - uridine diphosphate-glucuronosyl transferase. Genotyping for UGT1A1*28 before initiation of antiretroviral therapy containing atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Our objective was to estimate the prevalence of the UGTA1A1*28 polymorphism in HIV-infected individuals in Greece and to determine its potential association with hyperbilirubinaemia in patients receiving ATV/rit. The prevalence of the UGTA1A1*28 variant was estimated in 79 HIV-infected patients prior to the administration of the first-line treatment. The UGTA1A1*28 variant was detected in 46 out of 79 individuals (58.2%). Antiretroviral therapy was administered to 64/79 patients (81%). Among them, 26/64 (40.6%) received ATV/rit. Of the ATV/rit-treated patients, 14 were found to be carriers of the UGT1A1*28 variant (54%), and maximum serum bilirubin levels were significantly higher in the carrier population (4.71 vs. 2.69 mg/dL, p = 0.026). In 50% of the population, maximum levels were recorded in the first month of follow-up. Although carriage of UGT1A1 is linked with the development of hyperbilirubinaemia, the implementation of a pharmacogenomic approach in clinical practice cannot yet be recommended as a standard of care.

BACKGROUND & AIMS: HCV infection in haemodialysis (HD) patients is still a matter of investigation. The aim of this study was to determine the histology of chronic hepatitis C (CHC) in HCV-infected HD patients within the context of a comparative analysis including non-uraemic patients with CHC. The relative importance of virological, demographic and clinical parameters on disease manifestation was examined. METHODS: Sixty-one consecutive liver biopsies from HD patients and 326 from non-uraemic patients with chronic HCV infection were comparatively evaluated. RESULTS: Haemodialysis patients with CHC were older than control subjects (P = 0.031), showing a similar HCV genotype distribution (P = 0.328) and lower viral load (P = 0.001). CHC in HD patients was significantly milder according to stage (P = 0.033), grade and its parameters (periportal activity, portal inflammation and lobular activity) (P < 0.001). The frequency of lymphoid aggregates (10.2% vs. 50%, P < 0.001), bile duct lesions (1.7% vs. 22.1%, P < 0.001) and extent of steatosis (P = 0.022) in HD group was significantly reduced. Multivariate analysis showed that non-uraemic patients had 2.3 times higher risk of developing steatosis independently of genotype distribution and age. In HD group, genotype 3, longer HD duration and age at infection were significantly associated with steatosis, while older age at infection correlated with advanced fibrosis. CONCLUSIONS: Chronic hepatitis C in HD patients is usually very mild, losing its diagnostic histological features while patient's age and age at infection retain their prognostic significance. The weak inflammatory response, probably because of immunocompromised status and low viral load, may present a beneficial factor in the natural course of the disease.

Underwater geomorphological survey may reveal evidence of submerged tidal notches. In this paper, we present the methodology with the aim to reveal past temporary standstills of relative sea-level. Some examples of tidal notch development and tectonic movements are provided from fossil submerged notches mainly from Greece. A vertical movement causes a displacement of the intertidal bioerosion zone. For this reason the tidal notch profile reflects changes that occurred in the relative sea-level. If the movement is rapid a new tidal notch will be formed. On the contrary, if the movement is slower than the intertidal bioerosion rate, the height of the notch will increase. For this reason underwater marks on carbonate cliffs may provide evidence of recent vertical shoreline displacements of gradual or co-seismic origin.

In order to understand the linearization problem around a leaf of a singular foliation, we extend the familiar holonomy map from the case of regular foliations to the case of singular foliations. To this aim we introduce the notion of holonomy transformation. Unlike the regular case, holonomy transformations cannot be attached to classes of paths in the foliation, but rather to elements of the holonomy groupoid of the singular foliation.

On the basis of constrained density functional theory, we present ab initio calculations for the Hubbard U parameter of transition metal impurities in dilute magnetic semiconductors, choosing Mn in GaN as an example. The calculations are performed by two methods: (i) the Korringa-Kohn-Rostoker (KKR) Green function method for a single Mn impurity in GaN and (ii) the full-potential linearized augmented plane-wave (FLAPW) method for a large supercell of GaN with a single Mn impurity in each cell. By changing the occupancy of the majority t(2) gap state of Mn, we determine the U parameter either from the total energy differences E(N + 1) and E(N - 1) of the (N +/- 1) -electron excited states with respect to the ground state energy E(N), or by using the single-particle energies for n(0) +/- 1/2 occupancies around the charge-neutral occupancy n(0) (Janak's transition state model). The two methods give nearly identical results. Moreover the values calculated by the supercell method agree quite well with the Green function values. We point out an important difference between the `global' U parameter calculated using Janak's theorem and the `local' U of the Hubbard model.

Objectives: Immunoglobulin D (IgD) multiple myeloma is an uncommon variant of the disease probably associated with poorer prognosis. However, data on IgD myeloma patients treated in the novel agent era are lacking. Methods: To assess the frequency and the specific characteristics and evaluate the outcome of patients with IgD myeloma, we analyzed the database of the Greek Myeloma Study Group. Results: Between January 2000 and December 2012, among the 1239 patients with symptomatic myeloma, 31 (2.5%) were diagnosed with IgD myeloma. The median age of patients with IgD myeloma was 65 yr (range 26-80 yr) versus 68 yr (range 23-96 yr) of all others, and 84% had lambda light chain (vs. 38% of the patients with other subtypes). Patients with IgD myeloma presented more often with features of high-risk disease, that is, with advanced ISS, high LDH, significant renal dysfunction, and large amounts of Bence Jones proteinuria. Response to primary therapy was similar to other patients, although there was a trend for better quality of responses in patients with IgD myeloma. The median survival of these patients was 51.5 months versus 50.7 months for patients of other subtypes. In a multivariate model to adjust for differences in prognostic features, IgD myeloma was not associated with a different prognosis. Conclusion: The incidence of IgD myeloma is 2.5%. Although patients with IgD myeloma present more often with high-risk features, their outcome in the era of novel agents is similar to that of patients with other myeloma subtypes. © 2013 John Wiley & Sons A/S.

The study examines the performance of tax organizations in Greece, based on data obtained from a sample of 35 tax offices. Performance evaluation was conducted using DEA with bootstrap methods. In addition, Tobit regression analysis was employed to examine the environmental variables that impact on the efficiency performance of these tax offices. From the analysis, weaknesses, and management issues are derived from the tax offices inefficiency. The general conclusion is that a robust governance structure within the tax office operational framework is needed in order to improve organisational efficiency.

Blood transfusion is associated with well-known risks. We investigated the difference between a restrictive versus a liberal transfusion strategy on the immune response, as expressed by the production of inflammatory mediators, in patients subjected to major abdominal surgery procedures. Fifty-eight patients undergoing major abdominal surgery were randomized preoperatively to either a restrictive transfusion protocol or a liberal transfusion protocol (with transfusion if hemoglobin dropped below 7.7 g dL-1 or 9.9 g dL -1, respectively). In a subgroup of 20 patients randomly selected from the original allocation groups, blood was sampled for measurement of IL-6, IL-10, and TNFα. Postoperative levels of IL-10 were higher in the liberal transfusion group on the first postoperative day (49.82 ± 29.07 vs. 15.83 ± 13.22 pg mL-1, P < 0.05). Peak postoperative IL-10 levels correlated with the units of blood transfused as well as the mean duration of storage and the storage time of the oldest unit transfused (r 2 = 0.38, P = 0.032, r2 = 0.52, P = 0.007, and r 2 = 0.68, P < 0.001, respectively). IL-10 levels were elevated in patients with a more liberal red blood cell transfusion strategy. The strength of the association between anti-inflammatory IL-10 and transfusion variables indicates that IL-10 may be an important factor in transfusion-associated immunomodulation. This trial is registered under ClinicalTrials.gov Identifier: NCT02020525. © 2014 Kassiani Theodoraki et al.

The purpose of this article is to highlight and discuss the strategies used to diffuse and manage a primary ELT innovation in Greece, strategies that proved essential for developing stakeholders’ acceptance and ownership of the innovation, thereby facilitating its further development and sustainability. The PEAP Programme, launched in 2010, involved the introduction of EFL in the first and second grades of public primary schools in Greece. The extent of its impact and acceptance by teachers and other stakeholders was unexpected given the fact that the project was developed and implemented within a context of social and political instability and massive public sector and economic reform. The strategies reported in this article have implications for the successful management and implementation of primary EFL innovations in Europe and elsewhere.

The recent discovery of extragalactic PeV neutrinos opens a new window to the exploration of cosmic ray accelerators. The observed PeV neutrino flux is close to the Waxman-Bahcall upper bound implying that gamma-ray bursts (GRBs) may be the source of ultrahigh energy cosmic rays (UHECRs). Starting with the assumption of the GRB-UHECR connection, we show using both analytical estimates and numerical simulations that the observed neutrinos can originate at the jet as a result of photopion interactions with the following implications: the neutrino spectra are predicted to have a cut-off at energy ≲10 PeV; the dissipation responsible for the GRB emission and cosmic ray acceleration takes place at distances rdiss ≃ 3 × 1011-3 × 1013 cm from the central engine; the Thomson optical depth at the dissipation region is τT ∼ 1; the jet carries a substantial fraction of its energy in the form of Poynting flux at the dissipation region, and has a Lorentz factor Γ ≃ 100-500. The non-detection of PeV neutrinos coincident with GRBs will indicate that GRBs are either poor cosmic accelerators or the dissipation takes place at small optical depths in the jet.

The aim of this study was to identify volleyball performance indicators that best discriminate between winning and losing teams in a set according to set final score differences. The data were collected from teams’ performances (N=175) in all sets played during the 2009 Men’s European Volleyball Championship in Turkey. Clusters analysis established three different groups of sets according to set final score difference: 2 points (ambivalent), 3-5 points (safe), >5 points (unbalanced). A Wilcoxon signed rank test was performed on 10 performance indicators and 4 match indicators. The analysis revealed 11 important indicators for all sets have been played and for unbalanced set too, 7 important indicators for safe sets and 1 indicator for a m-bivalent sets. The analysis of ambivalent sets showed that the winning teams had a statistically significant (p <0.001) percentage of points from direct attack compared to the defeated teams. The resu lts confirm that coaches of men’s volleyball team should attach importance to improving offensive capacities of athletes

Background and aim of the study : Although anal cancer represents a relatively uncommon malignancy, its incidence over the last five decades, has been reported as increased for both sexes, worldwide. Human papillomavirus (HPV) infection has been shown to be a major cause for its development. The aim of the present study is to report on clinical, epidemiological and virological data of squamous anal cancer in Greek patients. Patients and Method : Between January 2002 and December 2010, 11 Greek patients (6 females) who were diagnosed as suffering from squamous cell anal or perianal cancer, were treated in our Hospital. Formalin fixed paraffin embedded tissue samples, obtained at the time of the anal biopsy or surgery, were analyzed by PCR in order to identify the presence as well as the type of HPV infection. Results : Overall, the presence of HPV DNA was detected in 6 out of the 11 patients (54.5%). The “highrisk” HPV DNA was  detected in 3 of them (2 women and 1 man), while the “lowrisk” HPV DNA was detected in the remaining three (2 women and 1 man). Conclusion : The incidence of HPV infection in squamous cell anal cancer Greek patients, is lower than other Western countries, probably reflecting differences in sexual habits in the Greek  population

BACKGROUND: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program. METHODS: Clinical, epidemiological and virological data from 4317 patients newly diagnosed with HIV-1 infection between 2002 and 2007 were analysed. Patients were enrolled using a pre-defined sampling strategy. RESULTS: The overall prevalence of TDRM in this period was 8.9% (95% CI: 8.1-9.8). Interestingly, significant changes over time in TDRM caused by the different drug classes were found. Whereas nucleoside resistance mutations remained constant at 5%, a significant decline in protease inhibitors resistance mutations was observed, from 3.9% in 2002 to 1.6% in 2007 (p = 0.001). In contrast, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) doubled from 2.0% in 2002 to 4.1% in 2007 (p = 0.004) with 58% of viral strains carrying a K103N mutation. Phylogenetic analysis showed that these temporal changes could not be explained by large clusters of TDRM. CONCLUSION: During the years 2002 to 2007 transmitted resistance to NNRTI has doubled to 4% in Europe. The frequent use of NNRTI in first-line regimens and the clinical impact of NNRTI mutations warrants continued monitoring.

OBJECTIVES: More than half of the diagnosed patients with bladder cancer (BCa) recur at least once following their initial treatment. Thus, patients' monitoring and prognosis is of utmost importance. However, the need for intensive surveillance of BCa significantly burdens patients' health-related quality of life. The aim of the present study is the expression analysis of BCL2L12, a recently identified member of the BCL2 apoptosis-related gene family, in BCa and the evaluation of BCL2L12 prognostic significance for the survival outcome of the patients. METHODS AND MATERIALS: Our study included 115 patients with BCa, and tissue specimens were obtained from the tumor area as well as from adjacent normal bladder wall. BCL2L12 expression was determined using quantitative real-time polymerase chain reaction assay, and was further correlated with patients' clinicopathological features and follow-up survival data. RESULTS: Up-regulated BCL2L12 expression levels were detected in malignant bladder specimens compared with normal ones. The higher BCL2L12 expression was further associated with shorter disease-free survival of the patients with BCa. Focusing on patients with TaT1 non-muscle invasive BCa, BCL2L12 expression levels were correlated with higher recurrence rate at the first follow-up cystoscopy and were unveiled to be an independent unfavorable predictor of patients' short-term recurrence following transurethral resection. Finally, BCL2L12 expression levels were also associated with poor disease-free survival of the high-grade TaT1 patients. CONCLUSIONS: Our data highlight the unfavorable prognostic value of BCL2L12 for patients with BCa and support its potential clinical use for the assessment of TaT1 patients' recurrence risk.

OBJECTIVE: To investigate the long-term psychological impact of intensive care unit (ICU) hospitalization, as well as to establish risk factors which successfully discriminate patients at higher risk. METHODS: The Medical Outcomes Study Short Form Survey (SF-36), the Center for Epidemiologic Studies for Depression (CES-D), and the Davidson Trauma Scale (DTS) questionnaires were obtained from 48 ICU survivors who were also interviewed and self-reported on several acknowledged risk factors. RESULTS: A high co-morbidity between depression and post-traumatic stress disorder (PTSD) cases was observed. Both CES-D and DTS scores correlated negatively with the SF-36 mental health subscale scores; although a causative relation cannot be attributed to this finding, it indicates a potential negative impact of depression and PTSD symptoms on the patients' quality of life even at 18- to 24-month post-ICU. The most important risk factor associated with a long-term impact on quality of life, depression and PTSD was lifetime history of any psychiatric disorder. CONCLUSIONS: During ICU admissions efforts should be made towards identifying and psychologically supporting those patients with a previous history of a psychiatric disease, as they are at considerably higher risk of suffering from the long-term psychological sequelae of ICU admission.

OBJECTIVE: To investigate dysferlin expression in muscle biopsies from patients with Duchenne muscular dystrophy (DMD). Dysferlin is known to have a role in the process of membrane fusion and muscle membrane repair in skeletal muscle fibers. STUDY DESIGN: We analyzed 20 muscle biopsy samples of DMD patients with immunohistochemical techniques to determine the expression of dysferlin. Immunoblotting was performed to assess dysferlin abundance in dystrophic muscle. RESULTS: Dysferlin showed various immunostaining patterns in dystrophic muscle, including reduced, normal, or enhanced sarcolemmal expression and intracellular immunostaining of the protein. Immunoblotting revealed that dysferlin was upregulated in 15 out of the 20 samples (75%). The abundance of the protein was analogous to the number of fibers with enhanced sarcolemmal expression of the protein. CONCLUSION: These data suggest that although dysferlin is not an integral part of the dystrophin-glycoprotein complex, its expression is altered in Duchenne muscular dystrophy.

Fluorine plasma treatment was investigated as an appropriate means for the surface modification of TiO2 thin film electrodes and the optimization of their performance as photoanodes in dye solar cells (DSCs) employing the Co(II)/(III) redox shuttle and the organic D35 sensitizer. Detailed surface and structural characterization of the titania films by contact angle measurements, atomic force microscopy, profilometry, and Raman and UV-vis spectroscopy showed that high density SF6 plasma provoked severe film densification and thus an increase of the nanoparticles packing density, leaving intact the crystallinity, particle size, and optical bandgap. Surface fluorination of the TiO2 films was also identified by X-ray photoelectron spectroscopy. The combination of the above effects resulted in the enhancement of both photocurrent and power conversion efficiency of the corresponding DSCs at moderate plasma treatment durations, while the photovoltage decreased continuously as a function of the fluorine processing time. Electrochemical impedance spectroscopy analysis revealed a marked increase of the density and distribution of trap states due to fluorine induced surface states along with a systematic downward shift of the TiO2 conduction band, probably attributed to the electrostatic coupling of intercalated Li + cations with the polar Ti-F species at the TiO2 surface, in agreement with the Voc drop. In contrast, enhanced electron injection was inferred to underlie the observed Jsc and DSC performance improvements, as surface fluorination and the concomitant film densification slightly increased electron transport while hardly affecting dye loading capacity, light harvesting efficiency, and recombination kinetics, except for the case of prolonged plasma treatment. Effective control of the detrimental side effects of fluorine species can render this kind of plasma treatment a powerful method to tune the surface and electrical properties of TiO2 films and optimize the behavior and performance of the resulting DSC devices. © 2014 American Chemical Society.

Group IVA cytosolic phospholipase A2 (GIVA cPLA2) is the rate-limiting provider of pro-inflammatory mediators in many tissues and is thus an attractive target for the development of novel anti-inflammatory agents. In this work, we present the synthesis of new thiazolyl ketones and the study of their activities in vitro, in cells, and in vivo. Within this series of compounds, methyl 2-(2-(4-octylphenoxy)acetyl)thiazole-4-carboxylate (GK470) was found to be the most potent inhibitor of GIVA cPLA2, exhibiting an XI(50) value of 0.011 mole fraction in a mixed micelle assay and an IC50 of 300 nM in a vesicle assay. In a cellular assay using SW982 fibroblast-like synoviocytes, it suppressed the release of arachidonic acid with an IC50 value of 0.6 μM. In a prophylactic collagen-induced arthritis model, it exhibited an anti-inflammatory effect comparable to the reference drug methotrexate, whereas in a therapeutic model, it showed results comparable to those of the reference drug Enbrel. In both models, it significantly reduced plasma PGE2 levels.

Island environments differ with regard to numerous features from the mainland and may induce large-scale changes in most aspects of the biology of an organism. In this study, we explore the effect of insularity on the morphology and performance of the feeding apparatus, a system crucial for the survival of organisms. To this end, we examined the head morphology and feeding ecology of island and mainland populations of the Balkan green lizard, Lacerta trilineata. We predicted that head morphology, performance and diet composition would differ between sexes and habitats as a result of varying sexual and natural selection pressures. We employed geometric morphometrics to test for differences in head morphology, measured bite forces and analysed the diet of 154 adult lizards. Morphological analyses revealed significant differences between sexes and also between mainland and island populations. Relative to females, males had larger heads, a stronger bite and consumed harder prey than females. Moreover, island lizards differed in head shape, but not in head size, and, in the case of males, demonstrated a higher bite force. Islanders had a wider food niche breadth and included more plant material in their diet. Our findings suggest that insularity influences feeding ecology and, through selection on bite force, head morphology. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, ●●, ●●–●●.

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

<p>Results from a high-resolution hindcast model experiment, supported by available observations, reveal an increasing salinity trend in the north Aegean during the Eastern Mediterranean Transient (EMT), largely controlled by increases in the flow rate and salinity of water masses of Levantine origin entering the domain through the Myconos-Ikaria strait as a response to an acceleration of the Aegean thermohaline cell. Changes in the Dardanelles inflow (increasing salinity) and in the surface freshwater flux (increasing Evaporation-Precipitation), although both contribute to a higher salt content of the basin during the EMT, play a minor role in the inter-annual/decadal variability of the freshwater budget. A long-term decreasing temperature trend is observed from the 1960s to the early 1990s. It is superimposed on the salinity-preconditioning phase over the 1980s and early 1990s. Both signals are, concomitantly, favouring conditions for intense Dense Water Formation (DWF) in the north Aegean Sea. In addition, the northward displacement of the Black Sea Water front over the EMT, leads to the expansion of convective cells towards the north and to higher formation rates associated with both colder and saltier surface waters.</p>

Purpose: To provide an update on recent advances in the management of patients with multiple myeloma who are not eligible for autologous stem-cell transplantation. Methods: A comprehensive review of the literature on diagnostic criteria is provided, and treatment options and management of adverse events are summarized. Results: Patients with symptomatic disease and organ damage (ie, hypercalcemia, renal failure, anemia, or bone lesions) require immediate treatment. The International Staging System and chromosomal abnormalities identify high- and standard-risk patients. Proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents are the most active agents. The presence of concomitant diseases, frailty, or disability should be assessed and, if present, treated with reduced-dose approaches. Bone disease, renal damage, hematologic toxicities, infections, thromboembolism, and peripheral neuropathy are the most frequent disabling events requiring prompt and active supportive care. Conclusion: These recommendations will help clinicians ensure the most appropriate care for patients with myeloma in everyday clinical practice. © 2014 by American Society of Clinical Oncology.

Recent developments have led to remarkable improvements in the assessment and treatment of patients with multiple myeloma (MM). New technologies have become available to precisely evaluate the biology and extent of the disease, including information about cytogenetics and genetic abnormalities, extramedullary manifestations and minimal residual disease. New, more effective drugs have been introduced into clinical practice, which enable clinicians to significantly improve the outcome of patients but also pose new challenges for the prevention and management of their specific side effects. Given these various new options and challenges, it is important to identify the minimal requirements for diagnosis and treatment of patients, as access to the most sophisticated advances may vary depending on local circumstances. Here, we propose the minimal requirements and possible options for diagnosis, monitoring and treatment of patients with multiple myeloma. © 2014 Macmillan Publishers Limited. All rights reserved.

This International Myeloma Working Group consensus updates the disease definition of multiple myeloma to include validated biomarkers in addition to existing requirements of attributable CRAB features (hypercalcaemia, renal failure, anaemia, and bone lesions). These changes are based on the identification of biomarkers associated with near inevitable development of CRAB features in patients who would otherwise be regarded as having smouldering multiple myeloma. A delay in application of the label of multiple myeloma and postponement of therapy could be detrimental to these patients. In addition to this change, we clarify and update the underlying laboratory and radiographic variables that fulfil the criteria for the presence of myeloma-defining CRAB features, and the histological and monoclonal protein requirements for the disease diagnosis. Finally, we provide specific metrics that new biomarkers should meet for inclusion in the disease definition. The International Myeloma Working Group recommends the implementation of these criteria in routine practice and in future clinical trials, and recommends that future studies analyse any differences in outcome that might occur as a result of the new disease definition. © 2014 Elsevier Ltd.

PURPOSE: To address the null hypothesis that surgeons shown radiographs of little finger metacarpal neck fractures with measured fracture angulation would recommend surgery as often as surgeons shown unmarked radiographs. METHODS: Members of the Science of Variation Group, an international collaboration of fully trained orthopedic and trauma surgeons, were asked to review 20 little finger metacarpal neck fracture cases, which included a vignette and 3 high-quality radiographs. Members were then randomized to review radiographs with or without measured fracture angulation on the lateral view and select operative or nonoperative management. RESULTS: Surgeons shown radiographs with measured angulation were more likely to recommend surgery, and there was less variability among these surgeons, particularly for fractures with less angular deformity. CONCLUSIONS: Measured fracture angulation has a small but significant influence on treatment recommendations for little finger metacarpal neck fractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III.

The general goal of this paper is to explore the potential of computer environments for the teaching and learning of functions. To address this, different theoretical frameworks and corresponding research traditions are available. In this study, we aim to network different frameworks by following a ‘double analysis’ method to analyse two empirical studies based on the use of computational environments offering integrated geometrical and algebraic representations. The studies took place in different national and didactic contexts and constitute cases of Constructionism and Theory of Didactical Situations. The analysis indicates that ‘double analysis’ resulted in a deepened and more balanced understanding about knowledge emerging from empirical studies as regards the nature of learning situations for functions with computers and the process of conceptualisation of functions by students. Main issues around the potential of computer environments for the teaching and learning of functions concern the use of integrated representations of functions linking geometry and algebra, the need to address epistemological and cognitive aspects of the constructed knowledge and the critical role of teachers in the design and evolution of students’ activity. We also reflect on how the networking of theories influences theoretical advancement and the followed research approaches.

The scope of this study was to investigate the uptake of chromium and nickel by onions (Allium cepa) and potatoes (Solanum tuberosum) and their impact on plant enzymes catalase (CAT, E.C. 1.11.1.6) and peroxidase (POX, E.C. 1.11.1.7). A greenhouse experiment was conducted, simulating the irrigating conditions existing in the two biggest tuber-producing regions of Greece (Asopos and Messapia). Plants were cultivated for 4 months in six irrigation lines, each one supplied by an aqueous solution, containing levels of Cr(VI) and Ni(II) ranging from 0 μg/L (control) to 1,000 μg/L. Significant statistical correlations were observed between (i) the levels of heavy metals in plants, (ii) the levels of heavy metals in plants and in irrigation water, and (iii) the levels of heavy metals and the enzymatic activities in plants. The existing EU legislation has no legal limits for Ni and Cr in food, and the nutritional implications of this study are discussed.

’Megaritiki’ is an olive cultivar widely used in Greece for the production of low polyphenol olive oil and table olives. To investigate possible metabolic differentiation in comparison with other varieties, the composition of ’Megaritiki’ olive fruits and wastewaters from the debittering procedure was studied. Moreover, the recovery of bioactive metabolites from wastewater using adsorption resin was studied to exploit this byproduct. Metabolites in fruits and wastewaters were monitored using NMR spectroscopy. The major constituents of wastewater were hydroxytyrosol-4-O-glucoside, 11-methyl-oleoside, hydroxytyrosol, and tyrosol but not oleuropein. Furthermore, wastewater afforded rengyoxide and rengyoside B, which are for the first time isolated from olives. The final edible olives, besides hydroxytyrosol and tyrosol, contained rengyoxide and cleroindicin C, which are the first isolated from the species, haleridone for the first time isolated from edible olives, and four metabolites, which are the first reported as natural products, megaritodilactone, megaritolactonic acid, methyl ester of megaritolactonic acid B, and megaritolactonol.

’Megaritiki’ is an olive cultivar widely used in Greece for the production of low polyphenol olive oil and table olives. To investigate possible metabolic differentiation in comparison with other varieties, the composition of ’Megaritiki’ olive fruits and wastewaters from the debittering procedure was studied. Moreover, the recovery of bioactive metabolites from wastewater using adsorption resin was studied to exploit this byproduct. Metabolites in fruits and wastewaters were monitored using NMR spectroscopy. The major constituents of wastewater were hydroxytyrosol-4-O-glucoside, 11-methyl-oleoside, hydroxytyrosol, and tyrosol but not oleuropein. Furthermore, wastewater afforded rengyoxide and rengyoside B, which are for the first time isolated from olives. The final edible olives, besides hydroxytyrosol and tyrosol, contained rengyoxide and cleroindicin C, which are the first isolated from the species, haleridone for the first time isolated from edible olives, and four metabolites, which are the first reported as natural products, megaritodilactone, megaritolactonic acid, methyl ester of megaritolactonic acid B, and megaritolactonol. © 2014 American Chemical Society.

El objetivo del presente estudio es examinar la influencia del tipo de tarea (narración - argumentación) en la fluidez y la exactitud léxica de la producción escrita de aprendientes griegos de español como lengua extranjera así como la posible interacción entre ellas dentro del mismo tipo de tarea. Los resultados han mostrado que el tipo de tarea influye tanto en la fluidez como en la exactitud léxica. En concreto, se ha observado mayor fluidez pero menor exactitud léxica en la tarea narrativa. Adicionalmente, se han observado correlaciones significativas entre la fluidez y la exactitud léxica solo en la tarea narrativa. Los resultados se explican basándose en el Modelo de la Capacidad Limitada de Atención de Skehan y la Hipótesis de Cognición de Robinson.  

Gastric cancer poses a significant public health problem, especially in the Far East, due to its high incidence in these areas. Surgical treatment and guidelines have been markedly different in the West, but nowadays this debate is apparently coming to an end. Laparoscopic surgery has been employed in the surgical treatment of gastric cancer for two decades now, but with controversies about the extent of resection and lymphadenectomy. Despite these difficulties, the apparent advantages of the laparoscopic approach helped its implementation in early stage and distal gastric cancer, with an increase on the uptake for distal gastrectomy for more advanced disease and total gastrectomy. Nevertheless, there is no conclusive evidence about the laparoscopic approach yet. In this review article we present and analyse the current status of laparoscopic surgery in the treatment of gastric cancer.

The author surveys Connes’ results on the longitudinal Laplace operator along a (regular) foliation and its spectrum, and discusses their generalization to any singular foliation on a compact manifold. Namely, it is proved that the Laplacian of a singular foliation is an essentially self-adjoint operator (unbounded) and has the same spectrum in every (faithful) representation, in particular, in L 2 of the manifold and L 2 of a leaf. The author also discusses briefly the relation of the Baum-Connes assembly map with the calculation of the spectrum.

We investigate the differences between an outflow in a highly resistive accretion disc corona, and the results with smaller or vanishing resistivity. For the first time, we determine conditions at the base of a two-dimensional radially self-similar outflow in the regime of very large resistivity. We performed simulations using the PLUTO magnetohydrodynamics (MHD) code, and found three modes of solutions. The first mode, with small resistivity, is similar to the ideal-MHD solutions. In the second mode, with larger resistivity, the geometry of the magnetic field changes, with a `bulge' above the superfast critical surface. At even larger resistivities, the third mode of solutions sets in, in which the magnetic field is no longer collimated, but is pressed towards the disc. This third mode is also the final one: it does not change with further increase of resistivity. These modes describe topological change in a magnetic field above the accretion disc because of the uniform, constant Ohmic resistivity.

We investigate the differences between an outflow in a highly resistive accretion disc corona, and the results with smaller or vanishing resistivity. For the first time, we determine conditions at the base of a two-dimensional radially self-similar outflow in the regime of very large resistivity. We performed simulations using the PLUTO magnetohydrodynamics (MHD) code, and found three modes of solutions. The first mode, with small resistivity, is similar to the ideal-MHD solutions. In the second mode, with larger resistivity, the geometry of the magnetic field changes, with a `bulge' above the superfast critical surface. At even larger resistivities, the third mode of solutions sets in, in which the magnetic field is no longer collimated, but is pressed towards the disc. This third mode is also the final one: it does not change with further increase of resistivity. These modes describe topological change in a magnetic field above the accretion disc because of the uniform, constant Ohmic resistivity.

We present an extension of the layer-multiple-scattering method to photonic crystals of gyrotropic spheres in a homogeneous host medium. The efficiency of the method is demonstrated on specific examples of three-dimensional chiral structures and surfaces of crystals of plasma spheres in an external static uniform magnetic field that lack, simultaneously, time-reversal and space-inversion symmetries, and exhibit a nonreciprocal spectral response.

The dorsiventral, amphistomatic, hairy, summer and winter leaves of Cistuscreticus had a secretory apparatus in which the secreted resinous material was not preserved in a cutinous wrap, as common during excretion in xerophytes, but was directly spread all over the protective trichomes and the leaf surface. Summer and winter leaves differed in trichome function and density, mesophyll structure, and compactness and secondary metabolite accumulation, mainly phenolics, secreted in excess in the mesophyll cells of the summer leaves. In vitro cell cultures may be used for the production of novel compounds from low-cost precursors. © 2014 Copyright Taylor & Francis Group, LLC.

Background: The combination melphalan-prednisone-thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches. Methods: We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT. Results: The median progression-free survival was 25.5 months with continuous lenalidomide-dexamethasone, 20.7 months with 18 cycles of lenalidomide-dexamethasone, and 21.2 months with MPT (hazard ratio for the risk of progression or death, 0.72 for continuous lenalidomide-dexamethasone vs. MPT and 0.70 for continuous lenalidomide-dexamethasone vs. 18 cycles of lenalidomide-dexamethasone; P<0.001 for both comparisons). Continuous lenalidomide-dexamethasone was superior to MPT for all secondary efficacy end points, including overall survival (at the interim analysis). Overall survival at 4 years was 59% with continuous lenalidomide-dexamethasone, 56% with 18 cycles of lenalidomide-dexamethasone, and 51% with MPT. Grade 3 or 4 adverse events were somewhat less frequent with continuous lenalidomide-dexamethasone than with MPT (70% vs. 78%). As compared with MPT, continuous lenalidomide-dexamethasone was associated with fewer hematologic and neurologic toxic events, a moderate increase in infections, and fewer second primary hematologic cancers. Conclusions: As compared with MPT, continuous lenalidomide-dexamethasone given until disease progression was associated with a significant improvement in progression-free survival, with an overall survival benefit at the interim analysis, among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation. Copyright © 2014 Massachusetts Medical Society.

The purpose of this pooled analysis was to synthesize all available data so as to evaluate the efficacy and safety of lenalidomide in patients with POEMS syndrome. Eligible articles were identified by a search in MEDLINE and ClinicalTrials.gov databases using a predefined combination. Eligible cases of patients treated in our department were additionally included. Overall, 51 patients were included. The median age of patients was 54.5 years (range: 32-79 years). Lenalidomide was given as first- or second-line treatment in 28.6% and 47.6% of patients, respectively. Hematological responses included complete response in 18.6%, very good partial response in 39.5% and partial response in 37.2% of cases. Vascular endothelial growth factor (VEGF) reduction was reported in all cases. Neuropathy improved in 92.0% of cases and stabilized in 8%. The progression-free survival (PFS) estimate at 12 months was 93.9%. Lenalidomide can represent a safe and effective option for the treatment of patients with POEMS. © 2014 Informa UK, Ltd.

In this issue of Blood, Farr et al showed that patients with monoclonal gammopathy of undetermined significance (MGUS) have increased cortical bone porosity and reduced bone strength,1 conditions that can lead to the increased fracture risk, which has been reported in MGUS patients. © 2014 by The American Society of Hematology.

Strawberry flavor is one of the most popular fruit flavors worldwide, with numerous applications in the food industry. In addition, the biosynthetic origin of the most important strawberry flavor components, such as 2,5-dimethyl-4-hydroxy-2H-furan-3-one (DMHF), is a challenging research area. DMHF's precursor, 2-hydroxy-propanal (or lactaldehyde), is biosynthesized by the endophytic bacterium Methylobacterium extorquens (M. extorquens). In particular, the alcohol dehydrogenase (ADH) enzymes of M. extorquens are involved in the biogenesis of DMHF precursors since they have the capacity to oxidize the strawberry-derived 1,2-propanediol to lactaldehyde. In this study, the expression of the endophytic ADH and the plant DMHF biosynthesis genes was examined in the tissues of raw and ripe strawberry receptacles by in situ hybridization. The presence of endophytic bacteria was studied in the same tissues by probes targeting bacterial 16S ribosomal ribonucleic acid. Hybridization signals of probes specific for endophytic ADH and plant DMHF biosynthesis genes, as well as bacteria-specific probes, were detected in the same locations. The probes were localized near the plasma membranes or intercellular spaces of cortical and vascular tissues of the receptacle, and intracellularly in the tissues of achenes. By localizing the expression of the endophytic methanol ADH and plant DMHF biosynthesis genes to the same tissues, we have reinforced our original hypothesis that an intimate symbiotic relationship between strawberry and endophytic cells exists and leads to the biosynthesis of DMHF.

In this paper we examine the relation of loneliness with psychopathology and psychotherapy. More specifically, first we present interpretations about the long-standing neglect of loneliness by the disciplines of Psychology and Psychiatry. Next, we analyze psychoanalytic and existential views from the clinical field about the associations between loneliness and psychopathology. We focus on narcissistic trauma and incapacity for love, as accompanying aspects of loneliness in many forms of psychopathology. Also, we discuss the role of loneliness in the psychotherapeutic relationship, according to the aforementioned views. Finally, we propose that we should recognize the paradoxical nature of loneliness, which means that this experience has both distressing and beneficial aspects, and that apart from being an inescapable universal condition, it may become an index of psychopathology as well.

Optimal treatment of chronic total occlusions (CTOs) remains one of the major challenges in interventional cardiology. A number of factors, including both patient clinical conditions and technical procedural considerations, have been identified to affect percutaneous coronary intervention (PCI) success and long-term outcomes, in large multicenter cohorts as well as smaller patient groups. As opposed to patient-centered factors, technical factors can be managed and as a result, a lot of research aims at improving stent technology and imaging guidance, toward enhancing PCI efficiency, in regards to patient safety.

A large number of prostate cancer (PCa) patients receive treatment without significant benefits, strengthening the need for accurate prognosis, which can be supported by the study of miRNAs. In silico specificity analysis was performed for the identification of miRNAs able to regulate KLK2 and KLK4 expression. Total RNA was extracted from prostate tissues obtained from PCa and benign prostate hyperplasia patients. Thereafter, RNA was polyadenylated and reverse transcribed to cDNA, which was used for qPCR analysis. miR-378 was predicted to target both KLK2 and KLK4 and downregulated levels detected in PCa patients (p=0.050). The reduction of miR-378 was correlated with higher Gleason score (p=0.018), larger diameter tumors (p=0.034), and elevated serum PSA (p=0.006). Regarding prognosis, miR-378 was able to improve risk stratification according to Gleason score or tumor stage, while higher risk to recur highlighted for the patients expressing lower miR-378 levels. Finally, the loss of miR-378 was able to predict the short-term relapse of 'high'- and 'very high'-recurrence-risk patients, independent of Gleason score, tumor stage, PSA, and age as indicated by Kaplan-Meier survival curves (p=0.030) and multivariate Cox regression analysis (p=0.018). In conclusion, loss of miR-378 expression increases the risk for PCa progression and relapse, despite active treatment.

Aim: The mesenchymal-epithelial transition factor (MET) is a receptor tyrosine kinase that plays a key role in cell survival, growth, angiogenesis and metastasis. Because its expression is frequently altered in tumors, MET is currently under investigation as a potential target for anticancer therapy. The purpose of the present study was to determine the prognostic value of tumor MET expression levels in patients with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-positive breast cancer, in order to strengthen the rationale for targeted therapy using MET inhibitors in this breast cancer subpopulation. Materials and Methods: We determined the expression of MET in formalin-fixed paraffin-embedded surgical specimens of ERand HER2-positive breast cancer by immunohistochemistry. Results: Comparisons of MET expression with clinical parameters, including survival of the patients, were performed with MET expression as a dichotomized variable classified as high or low. Out of 78 tumors, 3 (3.8%) showed high MET expression. The analysis examining the association between MET and survival did not yield any statistically significant result regarding overall survival or disease-free survival. Conclusion: ER- and HER2-positive breast carcinomas do not exhibit high MET expression. This null finding, the first to be reported in the literature, is of great importance, since it indicates that this sub-group population is not proper candidate for clinical trials with MET inhibitors.

The magnetic properties of double wall carbon nanotubes (DWCNTs) were investigated using electron spin resonance (ESR) spectroscopy. An asymmetric resonance line of low intensity was identified and analyzed by the superimposition of a narrow and a broad metallic lineshape, attributed to the distinct contributions of defect spins located on the inner and outer DWCNTs shells. The spin susceptibilities of both ESR components revealed a ferromagnetic phase transition at low temperatures (T<10K) with small variation in the corresponding Curie-Weiss temperatures, approaching closely that of metallic single wall carbon nanotubes. Interlayer coupling between the DWCNT layers is suggested to effectively reduce the difference between the transition temperatures for the inner and outer shells and enhance spin-spin interactions between defect spins via the RKKY-type interaction of localized spins with conduction electrons. © 2014 AIP Publishing LLC.

We report the detection of two M 31 novae as supersoft X-ray sources (SSS) in a recent XMM-Newton target of opportunity (ToO) observation. The 24 ks observation was obtained on 2014-08-09.89 UT to study the SSS emission of nova M31N 2014-02a, previously detected by Swift (ATel #6374).

To establish the effectiveness of interventions for the acute and long-term management of anaphylaxis, seven databases were searched for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series and - only in relation to adrenaline - case series investigating the effectiveness of interventions in managing anaphylaxis. Fifty-five studies satisfied the inclusion criteria. We found no robust studies investigating the effectiveness of adrenaline (epinephrine), H1-antihistamines, systemic glucocorticosteroids or methylxanthines to manage anaphylaxis. There was evidence regarding the optimum route, site and dose of administration of adrenaline from trials studying people with a history of anaphylaxis. This suggested that administration of intramuscular adrenaline into the middle of vastus lateralis muscle is the optimum treatment. Furthermore, fatality register studies have suggested that a failure or delay in administration of adrenaline may increase the risk of death. The main long-term management interventions studied were anaphylaxis management plans and allergen-specific immunotherapy. Management plans may reduce the risk of further reactions, but these studies were at high risk of bias. Venom immunotherapy may reduce the incidence of systemic reactions in those with a history of venom-triggered anaphylaxis.

The aim of the current study was to examine the relationship between cohesion and its antecedents (match participations, field position and length of team membership). 173 players of Greek amateur leagues participated in the study. They completed the Greek version of the 18-item Group Environment Questionnaire, and also improvised scales for the other variables in the end of the season 2009-2010. The Cronbach alphas of the Group Environment Questionnaire were satisfied for both task and social cohesion. The MANOVA analyses indicated the existence of statistical significant differences on perceptions of cohesion among players with different number of participations, and length of team membership. However, the MANOVA analysis showed that there were not statistical significant differences on perceptions of cohesion among players of different field position. Specifically, players with less participations perceived lower task and social cohesion than players with more participations. Furthermore, players who were members of their team for shorter period perceived lower social cohesion and higher task cohesion than players who were members for longer. Although the no significant results regarding the relationship between cohesion and field position, some trends showed that goalkeepers and attackers perceived the highest cohesion.

Background: The aim of this study was to determine maternal serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9), and MMP-9/NGAL complex longitudinally in pregnancy, in normal pregnancies, in pregnancies that developed preeclampsia and in pregnancies that delivered a small for gestational age infant (SGA). Methods: Neutrophil gelatinase-associated lipocalin, MMP-9, and MMP-9/NGAL were determined in the first, second, and third trimesters in 33 normal pregnancies, 12 pregnancies complicated by preeclampsia, and 14 pregnancies that delivered a SGA neonate. Results: Median NGAL concentration (ng/mL) in normal pregnancies increased significantly from 12.8 in the first trimester to 25.9 in the second trimester (p=0,002) and 48.0 (p<0.0001) in the third trimester. In preeclamptic pregnancies, NGAL was significantly higher, compared with normal pregnancies, in the first (30.9; p=0.006) and second (44.6; p=0.015) trimesters. MMP-9 and MMP-9/NGAL complex concentrations in preeclamptic pregnancies did not differ significantly from normal pregnancies in either trimester. Pregnancies with an SGA infant did not have different marker concentrations in either trimester, compared with normal pregnancies. Conclusion: Maternal serum NGAL, MMP-9, and MMP-9/NGAL complex concentrations tend to increase during pregnancy in normal and preeclamptic pregnancies. NGAL was significantly elevated in the first and second trimesters, in pregnancies that later developed preeclampsia. © 2014 John Wiley & Sons, Ltd.

Quinones are central intermediates in wine oxidation that can degrade the quality of wine by reactions with varietal thiols, such as 3-sulfanylhexanol, decreasing desirable aroma. Protection by wine preservatives (sulphur dioxide, glutathione, ascorbic acid and model tannin, phloroglucinol) was assessed by competitive sacrificial reactions with 4-methyl-1,2-benzoquinone, quantifying products and ratios by HPLC-UV-MS. Regioselectivity was assessed by product isolation and identification by NMR spectroscopy. Nucleophilic addition reactions compete with two electron reduction of quinones by sulphur dioxide or ascorbic acid, and both routes serve as effective quenching pathways, but minor secondary products from coupled redox reactions between the products and reactants are also observed. The wine preservatives were all highly reactive and thus all very protective against 3-sulfanylhexanol loss to the quinone, but showed only additive antioxidant effects. Confirmation of these reaction rates and pathways in wine is needed to assess the actual protective action of each tested preservative. © 2014 Elsevier Ltd. All rights reserved.

Quinones are central intermediates in wine oxidation that can degrade the quality of wine by reactions with varietal thiols, such as 3-sulfanylhexanol, decreasing desirable aroma. Protection by wine preservatives (sulphur dioxide, glutathione, ascorbic acid and model tannin, phloroglucinol) was assessed by competitive sacrificial reactions with 4-methyl-1,2-benzoquinone, quantifying products and ratios by HPLC-UV-MS. Regioselectivity was assessed by product isolation and identification by NMR spectroscopy. Nucleophilic addition reactions compete with two electron reduction of quinones by sulphur dioxide or ascorbic acid, and both routes serve as effective quenching pathways, but minor secondary products from coupled redox reactions between the products and reactants are also observed. The wine preservatives were all highly reactive and thus all very protective against 3-sulfanylhexanol loss to the quinone, but showed only additive antioxidant effects. Confirmation of these reaction rates and pathways in wine is needed to assess the actual protective action of each tested preservative.

OBJECTIVE: Adherence to a Mediterranean-style diet (MeDi) may protect against clinical vascular events by reducing atherosclerosis, but data is limited. This is the first observational study of the association between MeDi adherence and carotid plaque thickness and area. METHODS: The study included 1374 participants of the population-based Northern Manhattan Study with diet assessed and carotid intima-media thickness (cIMT) and plaque measured using B-mode ultrasound (mean age 66 ± 9 years, 60% female, 60% Hispanic, 18% White, 19% Black). A MeDi adherence score (range = 0-9, 9 representing maximal adherence) was examined continuously and in quintiles (3/4/5/6-9 vs. 0-2). RESULTS: Mean cIMT = 0.9 ± 0.1 mm and 57% had plaque (median plaque thickness = 1.5 mm, 75th percentile = 2.2; median plaque area = 4.2 mm(2), 75th percentile = 15.8). There was no association between MeDi and cIMT or plaque presence. MeDi adherence was inversely associated with the 75th percentile of plaque thickness and median of plaque area in quantile regression analyses. These associations persisted after controlling for demographics, smoking, physical activity, and total energy consumption (effect of a 1-point increase in MeDi score on the 75th percentile of plaque thickness = -0.049 mm, p = 0.03; median of plaque area = -0.371 mm(2), p = 0.03), and when additionally controlling for vascular disease biomarkers, medication use, BMI, and previous cardiac disease. The protective associations appeared strongest for those with a MeDi score of 5 (4th quintile) vs. 0-2 (bottom quintile). Differential effects of a MeDi on plaque thickness and area across race/ethnic groups was suggested. CONCLUSIONS: Moderate and strict adherence to a MeDi may protect against a higher burden of carotid atherosclerotic plaque, which may mediate the protection against clinical vascular events. Efforts to improve adherence to a MeDi are critical to reducing the burden of atherosclerotic disease.

Ferroelectric materials have attracted much interest due to their wide and important technological applications. Regarding their piezoelectric properties, these materials are evaluated by means of relatively complicate global methods. In this work a comparatively simple and efficient local method for the direct estimation of the d(ij) coefficients is presented. The method is based on conventional optical microscopy (OM) and advanced Atomic Force Microscopy (AFM) employed to image the local deformation of a specimen upon variation of a dc electric field. The feasibility and reliability of the method is demonstrated at room temperature in single crystals of (1-x)Pb(Mg1/3Nb2/3)O-3-xPbTiO(3). Non-homogeneous electromechanical processes are detected. Accordingly, the estimated d(ij) coefficients exhibit a spatial variation over the crystal surface. Except for electro-mechanical systems, the introduced local method could find wide application for the investigation of spatially non-homogeneous properties that possibly exist in relevant magneto-mechanical and thermo-mechanical complex systems. (C) 2014 Elsevier B.V. All rights reserved.

Breast cancer (BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, prognostic or predictive usefulness as well as therapeutic value for BC. Micro-RNAs (miRNAs) belong to a novel class of endogenous interfering RNAs that play a crucial role in post transcriptional gene silencing through mRNA targeting and, thus, are involved in many biological processes encompassing apoptosis, cell-cycle control, cell proliferation, DNA repair, immunity, metabolism, stress, aging, etc. MiRNAs exert their action mainly in a tumor suppressive or oncogenic manner. The specific aberrant expression patterns of miRNAs in BC that are detected with the use of high-throughput technologies reflect their key role in cancer initiation, progression, migration, invasion and metastasis. The detection of circulating extracellular miRNAs in plasma of BC patients may provide novel, non-invasive biomarkers in favor of BC diagnosis and prognosis and, at the same time, accumulating evidence has underscored the possible contribution of miRNAs as valuable biomarkers to predict response to chemotherapy or radiotherapy. Data from in vitro and in vivo studies on BC have revealed promising therapeutic approaches via miRNA delivery and miRNA inhibition. The purpose of this review is to explore the ontological role of miRNAs in BC etiopathogenesis as well as to highlight their potential, not only as non-invasive circulating biomarkers with diagnostic and prognostic significance, but also as treatment response predictors and therapeutic targets aiding BC management.

MicroRNAs (miRNAs) have emerged as potent modulators of mammalian gene expression, thereby broadening the spectrum of molecular mechanisms orchestrating human physiological and pathological cellular functions. Growing evidence suggests that these small non-coding RNA molecules are pivotal regulators of cardiovascular development and disease. Importantly, multiple miRNAs have been specifically implicated in the onset and progression of heart failure, thus providing a new platform for battling this multi-faceted disease. This review introduces the basic concepts of miRNA biology, describes representative examples of miRNAs associated with multiple aspects of HF pathogenesis, and explores the prognostic, diagnostic and therapeutic potential of miRNAs in the cardiology clinic.

Mitochondria are highly dynamic organelles and their proper function is crucial for the maintenance of cellular homeostasis. Mitochondrial biogenesis and mitophagy are two pathways that regulate mitochondrial content and metabolism preserving homeostasis. The tight regulation between these opposing processes is essential for cellular adaptation in response to cellular metabolic state, stress and other intracellular or environmental signals. Interestingly, imbalance between mitochondrial proliferation and degradation process results in progressive development of numerous pathologic conditions. Here we review recent studies that highlight the intricate interplay between mitochondrial biogenesis and mitophagy, mainly focusing on the molecular mechanisms that govern the coordination of these processes and their involvement in age-related pathologies and ageing.

Allergy to banana fruit appears to have become an important cause of fruit allergy in Europe. Among five allergens that have been found, beta-1,3-glucanase denoted as Mus a 5 was identified as a candidate allergen for the component-resolved allergy diagnosis of banana allergy. Because of the variations in protein levels in banana fruit, in this study Mus a 5 was produced as a fusion protein with glutathione-S-transferase in Escherichia coli. The recombinant Mus a 5 was purified under native conditions by a combination of affinity, ion-exchange, and reversed phase chromatography. N-terminal sequence was confirmed by Edman degradation and 55 % of the primary structure was identified by mass fingerprint, while the secondary structure was assessed by circular dichroism spectroscopy. IgG reactivity of recombinant protein was shown in 2-D immunoblot with anti-Mus a 5 antibodies, while IgG and IgE binding to natural Mus a 5 was inhibited with the recombinant Mus a 5 in immunoblot inhibition test. IgE reactivity of recombinant Mus a 5 was shown in ELISA within a group of ten persons sensitized to banana fruit. Recombinant Mus a 5 is a novel reagent suitable for the component-resolved allergy diagnosis of banana allergy.

{This study investigated the effects of short-term eccentric exercise training using a custom-made isokinetic leg press device, on concentric and eccentric strength and explosiveness as well as jumping performance. Nineteen healthy males were divided into an eccentric (ECC

{This study investigated the effects of short-term eccentric exercise training using a custom-made isokinetic leg press device, on concentric and eccentric strength and explosiveness as well as jumping performance. Nineteen healthy males were divided into an eccentric (ECC

We present an extended version of the layer-multiple-scattering method, which is ideally suited for the study of photonic crystals of different kinds of particles, encompassing homogeneous and multicoated chiral and nonchiral spheres, gyrotropic spheres, as well as homogeneous nonspherical particles. The efficiency of the method is demonstrated on specific examples of planar magnetoplasmonic nanostructures that lack, simultaneously, time-reversal and space-inversion symmetries. Nonreciprocal transport of light at the (001) surface of a semi-infinite face centered cubic (fcc) crystal of plasma nanospheres under the action of an external, in-plane, static magnetic field and of surface plasmon polaritons at the surface of a plasmonic material coated with an overlayer of magnetized garnet nanospheres is demonstrated in the Voigt geometry.

Muscle lim protein (MLP) has emerged as a critical regulator of striated muscle physiology and pathophysiology. Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, have been directly associated with human cardiomyopathies, whereas aberrant expression patterns are reported in human cardiac and skeletal muscle diseases. Increasing evidence suggests that MLP has an important role in both myogenic differentiation and myocyte cytoarchitecture, although the full spectrum of its intracellular roles has not been delineated. We report the discovery of an alternative splice variant of MLP, designated as MLP-b, showing distinct expression in neuromuscular disease and direct roles in actin dynamics and muscle differentiation. This novel isoform originates by alternative splicing of exons 3 and 4. At the protein level, it contains the N-terminus first half LIM domain of MLP and a unique sequence of 22 amino acids. Physiologically, it is expressed during early differentiation, whereas its overexpression reduces C2C12 differentiation and myotube formation. This may be mediated through its inhibition of MLP/cofilin-2-mediated F-actin dynamics. In differentiated striated muscles, MLP-b localizes to the sarcomeres and binds directly to Z-disc components, including α-actinin, T-cap and MLP. The findings of the present study unveil a novel player in muscle physiology and pathophysiology that is implicated in myogenesis as a negative regulator of myotube formation, as well as in differentiated striated muscles as a contributor to sarcomeric integrity.

Muscle lim protein (MLP) has emerged as a critical regulator of striated muscle physiology and pathophysiology. Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, have been directly associated with human cardiomyopathies, whereas aberrant expression patterns are reported in human cardiac and skeletal muscle diseases. Increasing evidence suggests that MLP has an important role in both myogenic differentiation and myocyte cytoarchitecture, although the full spectrum of its intracellular roles has not been delineated. We report the discovery of an alternative splice variant of MLP, designated as MLP-b, showing distinct expression in neuromuscular disease and direct roles in actin dynamics and muscle differentiation. This novel isoform originates by alternative splicing of exons 3 and 4. At the protein level, it contains the N-terminus first half LIM domain of MLP and a unique sequence of 22 amino acids. Physiologically, it is expressed during early differentiation, whereas its overexpression reduces C2C12 differentiation and myotube formation. This may be mediated through its inhibition of MLP/cofilin-2-mediated F-actin dynamics. In differentiated striated muscles, MLP-b localizes to the sarcomeres and binds directly to Z-disc components, including alpha-actinin, T-cap and MLP. The findings of the present study unveil a novel player in muscle physiology and pathophysiology that is implicated in myogenesis as a negative regulator of myotube formation, as well as in differentiated striated muscles as a contributor to sarcomeric integrity.

BACKGROUND: The ability to predict the length of time to death and institutionalization has strong implications for Alzheimer's disease patients and caregivers, health policy, economics, and the design of intervention studies. OBJECTIVE: To develop and validate a prediction algorithm that uses data from a single visit to estimate time to important disease endpoints for individual Alzheimer's disease patients. METHOD: Two separate study cohorts (Predictors 1, N = 252; Predictors 2, N = 254), all initially with mild Alzheimer's disease, were followed for 10 years at three research centers with semiannual assessments that included cognition, functional capacity, and medical, psychiatric, and neurologic information. The prediction algorithm was based on a longitudinal Grade of Membership model developed using the complete series of semiannually-collected Predictors 1 data. The algorithm was validated on the Predictors 2 data using data only from the initial assessment to predict separate survival curves for three outcomes. RESULTS: For each of the three outcome measures, the predicted survival curves fell well within the 95% confidence intervals of the observed survival curves. Patients were also divided into quintiles for each endpoint to assess the calibration of the algorithm for extreme patient profiles. In all cases, the actual and predicted survival curves were statistically equivalent. Predictive accuracy was maintained even when key baseline variables were excluded, demonstrating the high resilience of the algorithm to missing data. CONCLUSION: The new prediction algorithm accurately predicts time to death, institutionalization, and need for full-time care in individual Alzheimer's disease patients; it can be readily adapted to predict other important disease endpoints. The algorithm will serve an unmet clinical, research, and public health need.

Treatment in medical oncology is gradually shifting from the use of nonspecific chemotherapeutic agents toward an era of novel targeted therapy in which drugs and their combinations target specific aspects of the biology of tumor cells. Multiple myeloma (MM) has become one of the best examples in this regard, reflected in the identification of new pathogenic mechanisms, together with the development of novel drugs that are being explored from the preclinical setting to the early phases of clinical development. We review the biological rationale for the use of the most important new agents for treating MM and summarize their clinical activity in an increasingly busy field. First, we discuss data from already approved and active agents (including second- and third-generation proteasome inhibitors (PIs), immunomodulatory agents and alkylators). Next, we focus on agents with novel mechanisms of action, such as monoclonal antibodies (MoAbs), cell cycle-specific drugs, deacetylase inhibitors, agents acting on the unfolded protein response, signaling transduction pathway inhibitors and kinase inhibitors. Among this plethora of new agents or mechanisms, some are specially promising: anti-CD38 MoAb, such as daratumumab, are the first antibodies with clinical activity as single agents in MM. Moreover, the kinesin spindle protein inhibitor Arry-520 is effective in monotherapy as well as in combination with dexamethasone in heavily pretreated patients. Immunotherapy against MM is also being explored, and probably the most attractive example of this approach is the combination of the anti-CS1 MoAb elotuzumab with lenalidomide and dexamethasone, which has produced exciting results in the relapsed/refractory setting. © 2014 Macmillan Publishers Limited.

The Elefsis Bay is a typical coastal setting characterized by a semi-closed shallow environment with intense anthropogenic activity. This study describes a peculiar low cell density and species poor late-winter coccolithophore assemblages from Elefsis Bay compared to those from further offshore of the Aegean Sea. Helicosphaera carteri contributes significantly to the assemblage inside the Elefsis Bay and together with Emiliania huxleyi both represent the dominant component of the calcareous nannoplankton. Water column data confirmed the opportunistic behavior of H. carteri, thus providing new evidence for the ecology of the species. It is suggested that an increase in this species can be associated with distinct pollution in neritic environments. 

The effectiveness of radiotherapy in patients with basal cell carcinoma (BCC) has been already reported in the literature. However, there is little information about the irradiation of BCC in elderly patients, especially due to the low conformity of them to daily irradiation. Thirty-eight retrospectively selected elderly patients (78 years as median age) diagnosed with skin BCC of the head and neck area were treated with five weekly fractions of 600 cGy by three-dimensional conformal radiotherapy (3DCRT) as an adjuvant treatment. The primary endpoint was the relapse free survival. Acute toxicity, as secondary endpoint, was assessed according to EORTC/RTOG criteria. Among our patients, there were only three local recurrences at 15, 32 and 38 months post-3DCRT. There was no severe toxicity, while only 10 out of 38 patients presented grade II/III skin toxicity. Our proposed irradiation schedule seems effective in terms of local control and acute toxicity and could be an alternative scheme for elderly patients unfit for daily irradiation.

The Collective Article ‘New Mediterranean Biodiversity Records’ of the Mediterranean Marine Science journal offers the means to publish biodiversity records in the Mediterranean Sea. The current article is divided in two parts, for records of alien and native species respectively. The new records of alien species include: the red alga Asparagopsis taxiformis (Crete and Lakonikos Gulf, Greece); the red alga Grateloupia turuturu (along the Israeli Mediterranean shore); the mantis shrimp Clorida albolitura (Gulf of Antalya, Turkey); the mud crab Dyspanopeus sayi (Mar Piccolo of Taranto, Ionian Sea); the blue crab Callinectes sapidus (Chios Island, Greece); the isopod Paracerceis sculpta (northern Aegean Sea, Greece); the sea urchin Diadema setosum (Gökova Bay, Turkey); the molluscs Smaragdia souverbiana, Murex forskoehlii, Fusinus verrucosus, Circenita callipyga, and Aplysia dactylomela (Syria); the cephalaspidean mollusc Haminoea cyanomarginata (Baia di Puolo, Massa Lubrense, Campania, southern Italy); the topmouth gudgeon Pseudorasbora parva (Civitavecchia, Tyrrhenian Sea); the fangtooth moray Enchelycore anatine (Plemmirio marine reserve, Sicily); the silver-cheeked toadfish Lagocephalus sceleratus (Saros Bay, Turkey; and Ibiza channel, Spain); the Indo-Pacific ascidian Herdmania momus in Kastelorizo Island (Greece); and the foraminiferal Clavulina multicamerata (Saronikos Gulf, Greece). The record of L. sceleratus in Spain consists the deepest (350-400m depth) record of the species in the Mediterranean Sea. The new records of native species include: first record of the ctenophore Cestum veneris in Turkish marine waters; the presence of Holothuria tubulosa and Holothuria polii in the Bay of Igoumenitsa (Greece); the first recorded sighting of the bull ray Pteromylaeus bovinus in Maltese waters; and a new record of the fish Lobotes surinamensis from Maliakos Gulf.

ΚΑΝΟΝ ΧΧΙΙ, Jahrbuch der Gesellschaft fur das Recht der Ostkirchen, Partilularrecht. ed. Roman Kovar, Hennef 2014

The Notch signaling pathway controls cell fates through interactions between neighboring cells by positively or negatively affecting the processes of proliferation, differentiation and apoptosis in a context-dependent manner. This pathway has been implicated in human cancer as both an oncogene and a tumor suppressor. Here we report new inactivating mutations in Notch pathway components in over 40% of human bladder cancers examined. Bladder cancer is the fourth most commonly diagnosed malignancy in the male population of the United States. Thus far, driver mutations in fibroblast growth factor receptor 3 (FGFR3) and, less commonly, in RAS proteins have been identified. We show that Notch activation in bladder cancer cells suppresses proliferation both in vitro and in vivo by directly upregulating dual-specificity phosphatases (DUSPs), thus reducing the phosphorylation of ERK1 and ERK2 (ERK1/2). In mouse models, genetic inactivation of Notch signaling leads to Erk1/2 phosphorylation, resulting in tumorigenesis in the urinary tract. Collectively our findings show that loss of Notch activity is a driving event in urothelial cancer.

The purpose of the present work is to develop a non-binary biopharmaceutical classification system the so called AB Gamma system. The original mathematical model used for the development of BCS, appropriately modified, was applied to estimate the limiting values of drug solubility and permeability when the fraction of dose absorbed, Fa, was 0.90 or 0.20. The AB Gamma system is based on the fraction of dose absorbed and relies on permeability, solubility plane. The first category (A, alpha) includes drugs with Fa = 0.90, whereas the B (beta) category consists of drugs with Fa = 0.20. The area lying between the two boundaries of A and B defines the third category (gamma), Gamma, (0.20 < Fa < 0.90). For comparative purposes, the BCS classes I-IV were co-plotted together with the AB Gamma system. Most of the BCS classes II and III are included in category Gamma which mainly consists of drugs with properties like moderate or low solubility and permeability. Due to the dynamic character of dissolution and uptake processes, category A is expanded toward BCS Class II. The AB Gamma system allows the classification of all compounds into three categories (A, B, Gamma) in terms of the fraction of dose absorbed. (C) 2014 Elsevier B. V. All rights reserved.

It is shown that a planar defect in the stacking sequence of an all-dielectric photonic crystal of garnet spheres supports localized optical guided modes, which originate from Mie resonances of the individual spheres. If the defect breaks space-inversion symmetry and the garnet particles are magnetized inplane, nonreciprocal and lossless transport of light on the defect plane, expected on the basis of group theory in the Voigt–Cotton–Mouton configuration, is demonstrated in ultrathin films of the defect crystal by means of full electrodynamic calculations using the layer-multiple-scattering method properly extended to photonic crystals of gyrotropic spheres.

Tornadoes have been reported in Greece over recent decades in specific sub-geographical areas and have been associated with strong synoptic forcing. While it has been established that meteorological conditions over Greece are affected at various scales by the significant variability of topography, the Ionian Sea to the west and the Aegean Sea to the east, there is still uncertainty regarding topography's importance on tornadic generation and development. The aim of this study is to investigate the role of topography in significant tornadogenesis events that were triggered under strong synoptic scale forcing over Greece. Three tornado events that occurred over the last years in Thebes (Boeotia, 17 November 2007), Vrastema (Chalkidiki, 12 February 2010) and Vlychos (Lefkada, 20 September 2011) were selected for numerical experiments. These events were associated with synoptic scale forcing, while their intensities were T4-T5 (on the TORRO scale), causing significant damage. The simulations were performed using the non-hydrostatic weather research and forecasting model (WRF), initialized by European Centre for Medium-Range Weather Forecasts (ECMWF) gridded analyses, with telescoping nested grids that allow for the representation of atmospheric circulations ranging from the synoptic scale down to the mesoscale. In the experiments, the topography of the inner grid was modified by: (a) 0% (actual topography) and (b)-100% (without topography), making an effort to determine whether the occurrence of tornadoes-mainly identified by various severe weather instability indices-could be indicated by modifying topography. The principal instability variables employed consisted of the bulk Richardson number (BRN) shear, the energy helicity index (EHI), the storm-relative environmental helicity (SRH), and the maximum convective available potential energy (MCAPE, for parcels with maximum (θe). Additionally, a model verification was conducted for every sensitivity experiment accompanied by analysis of the absolute vorticity budget. Numerical simulations revealed that the complex topography constituted an important factor during the 17 November 2007 and 12 February 2010 events, based on EHI, SRH, BRN, and MCAPE analyses. Conversely, topography around the 20 September 2011 event was characterized as the least significant factor based on EHI, SRH, BRN, and MCAPE analyses. © 2014 Author(s).

BACKGROUND: Austerity measures and health-system redesign to minimise hospital expenditures risk adversely affecting patient outcomes. The RN4CAST study was designed to inform decision making about nursing, one of the largest components of hospital operating expenses. We aimed to assess whether differences in patient to nurse ratios and nurses' educational qualifications in nine of the 12 RN4CAST countries with similar patient discharge data were associated with variation in hospital mortality after common surgical procedures. METHODS: For this observational study, we obtained discharge data for 422,730 patients aged 50 years or older who underwent common surgeries in 300 hospitals in nine European countries. Administrative data were coded with a standard protocol (variants of the ninth or tenth versions of the International Classification of Diseases) to estimate 30 day in-hospital mortality by use of risk adjustment measures including age, sex, admission type, 43 dummy variables suggesting surgery type, and 17 dummy variables suggesting comorbidities present at admission. Surveys of 26,516 nurses practising in study hospitals were used to measure nurse staffing and nurse education. We used generalised estimating equations to assess the effects of nursing factors on the likelihood of surgical patients dying within 30 days of admission, before and after adjusting for other hospital and patient characteristics. FINDINGS: An increase in a nurses' workload by one patient increased the likelihood of an inpatient dying within 30 days of admission by 7% (odds ratio 1·068, 95% CI 1·031-1·106), and every 10% increase in bachelor's degree nurses was associated with a decrease in this likelihood by 7% (0·929, 0·886-0·973). These associations imply that patients in hospitals in which 60% of nurses had bachelor's degrees and nurses cared for an average of six patients would have almost 30% lower mortality than patients in hospitals in which only 30% of nurses had bachelor's degrees and nurses cared for an average of eight patients. INTERPRETATION: Nurse staffing cuts to save money might adversely affect patient outcomes. An increased emphasis on bachelor's education for nurses could reduce preventable hospital deaths. FUNDING: European Union's Seventh Framework Programme, National Institute of Nursing Research, National Institutes of Health, the Norwegian Nurses Organisation and the Norwegian Knowledge Centre for the Health Services, Swedish Association of Health Professionals, the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet, Committee for Health and Caring Sciences and Strategic Research Program in Care Sciences at Karolinska Institutet, Spanish Ministry of Science and Innovation.

BACKGROUND: Despite concerns as to whether nurses can perform reliably and effectively when working longer shifts, a pattern of two 12- to 13-hour shifts per day is becoming common in many hospitals to reduce shift to shift handovers, staffing overlap, and hence costs. OBJECTIVES: To describe shift patterns of European nurses and investigate whether shift length and working beyond contracted hours (overtime) is associated with nurse-reported care quality, safety, and care left undone. METHODS: Cross-sectional survey of 31,627 registered nurses in general medical/surgical units within 488 hospitals across 12 European countries. RESULTS: A total of 50% of nurses worked shifts of ≤ 8 hours, but 15% worked ≥ 12 hours. Typical shift length varied between countries and within some countries. Nurses working for ≥ 12 hours were more likely to report poor or failing patient safety [odds ratio (OR)=1.41; 95% confidence interval (CI), 1.13-1.76], poor/fair quality of care (OR=1.30; 95% CI, 1.10-1.53), and more care activities left undone (RR=1.13; 95% CI, 1.09-1.16). Working overtime was also associated with reports of poor or failing patient safety (OR=1.67; 95% CI, 1.51-1.86), poor/fair quality of care (OR=1.32; 95% CI, 1.23-1.42), and more care left undone (RR=1.29; 95% CI, 1.27-1.31). CONCLUSIONS: European registered nurses working shifts of ≥ 12 hours and those working overtime report lower quality and safety and more care left undone. Policies to adopt a 12-hour nursing shift pattern should proceed with caution. Use of overtime working to mitigate staffing shortages or increase flexibility may also incur additional risk to quality.

The purpose of this study is register the opinion of nurses on the compatibility of the Nursing Information System with the provision of nursing care, and the ease of learning of the subsystem. This paper is an empirical study that was conducted using a questionnaire in Cancer and Oncology Hospital "Agios Savvas". Specifically, 121 nurses (108 women and 13 men) of all education levels participated in the survey. According to user responses, 86% agreed partially that the subsystem was easy to learn, and 40.5 % of this 86% believe that the clinical subsystem adequately supports nursing care, mainly engaged in designing the necessary processes, and followed by reducing errors. In conclusion, we can consider that the use of information systems in nursing is important for improving clinical practice and quality of patient care.

Oleuropein is a bioactive natural product from olives known to display a broad variety of health beneficial properties. However its presence in most edible olives is lowered due to debittering. In this respect, we envisaged the incorporation of oleuropein into dairy products (cow’s milk and yogurt) aiming to produce novel functional foods. Additionally, an analytical method for the monitoring of oleuropein in milk and yogurt was also developed and validated. Oleuropein was not affected during heat treatment of milk, while during the milk fermentation process it was not hydrolysed by the produced acids. Oleuropein was not metabolised by lactic acid bacteria, did not inhibit their growth and its stability in the final products was proven. The novel products displayed same taste, colour and texture as the conventional ones. Results herein indicate that oleuropein can be added as an active ingredient in milk and yogurt preparations to provide two novel functional dairy products. © 2014 Published by Elsevier Ltd.

Oleuropein is a bioactive natural product from olives known to display a broad variety of health beneficial properties. However its presence in most edible olives is lowered due to debittering. In this respect, we envisaged the incorporation of oleuropein into dairy products (cow’s milk and yogurt) aiming to produce novel functional foods. Additionally, an analytical method for the monitoring of oleuropein in milk and yogurt was also developed and validated. Oleuropein was not affected during heat treatment of milk, while during the milk fermentation process it was not hydrolysed by the produced acids. Oleuropein was not metabolised by lactic acid bacteria, did not inhibit their growth and its stability in the final products was proven. The novel products displayed same taste, colour and texture as the conventional ones. Results herein indicate that oleuropein can be added as an active ingredient in milk and yogurt preparations to provide two novel functional dairy products.

Aims: We investigate the role of the second synchrotron self-Compton (SSC) photon generation to the multiwavelength emission from the compact regions of sources that are characterized as misaligned blazars. For this, we focus on the nearest high-energy emitting radio galaxy Centaurus A and we revisit the one-zone SSC model for its core emission. Methods: We have calculated analytically the peak luminosities of the first and second SSC components by first deriving the steady-state electron distribution in the presence of synchrotron and SSC cooling, and then by using appropriate expressions for the positions of the spectral peaks. We have also tested our analytical results against those derived from a numerical code where the full emissivities and cross-sections were used. Results: We show that the one-zone SSC model cannot account for the core emission of Centaurus A above a few GeV, where the peak of the second SSC component appears. We thus propose an alternative explanation for the origin of the high-energy (≳0.4 GeV) and TeV emission, where these are attributed to the radiation emitted by a relativistic proton component through photohadronic interactions with the photons produced by the primary leptonic component. We show that the required proton luminosities are not extremely high, i.e. ~1043 erg/s, provided that the injection spectra are modelled by a power law with a high value of the lower energy cutoff. Finally, we find that the contribution of the core emitting region of Cen A to the observed neutrino and ultra-high-energy cosmic-ray fluxes is negligible.

Aims: We investigate the role of the second synchrotron self-Compton (SSC) photon generation to the multiwavelength emission from the compact regions of sources that are characterized as misaligned blazars. For this, we focus on the nearest high-energy emitting radio galaxy Centaurus A and we revisit the one-zone SSC model for its core emission. Methods: We have calculated analytically the peak luminosities of the first and second SSC components by first deriving the steady-state electron distribution in the presence of synchrotron and SSC cooling, and then by using appropriate expressions for the positions of the spectral peaks. We have also tested our analytical results against those derived from a numerical code where the full emissivities and cross-sections were used. Results: We show that the one-zone SSC model cannot account for the core emission of Centaurus A above a few GeV, where the peak of the second SSC component appears. We thus propose an alternative explanation for the origin of the high-energy (≳0.4 GeV) and TeV emission, where these are attributed to the radiation emitted by a relativistic proton component through photohadronic interactions with the photons produced by the primary leptonic component. We show that the required proton luminosities are not extremely high, i.e. ~1043 erg/s, provided that the injection spectra are modelled by a power law with a high value of the lower energy cutoff. Finally, we find that the contribution of the core emitting region of Cen A to the observed neutrino and ultra-high-energy cosmic-ray fluxes is negligible.

The following paper presents a scientific contribution that explores the clinicians' use of online information retrieval systems for their clinical decision making. Particularly, the research focuses on the ability of doctors and nurses in seeking information through MEDLINE and ScienceDirect. The research process took place by an electronic form consisted of five clinical scenarios and an evaluation sheet. The results testify that only a small percent of clinicians use the recommended electronic bibliographic databasesand take the right clinical decision to the scenarios. Health professionals have to be educated in information searching and take advantage from the provided literature taking more useful and reliable answers on their clinical questions.

BACKGROUND: Patterns of health-care use and comorbidities present in patients in the period before diagnosis of chronic obstructive pulmonary disease (COPD) are unknown. We investigated these factors to inform future case-finding strategies. METHODS: We did a retrospective analysis of a clinical cohort in the UK with data from Jan 1, 1990 to Dec 31, 2009 (General Practice Research Database and Optimum Patient Care Research Database). We assessed patients aged 40 years or older who had an electronically coded diagnosis of COPD in their primary care records and had a minimum of 3 years of continuous practice data for COPD (2 years before diagnosis up to a maximum of 20 years, and 1 year after diagnosis) and at least two prescriptions for COPD since diagnosis. We identified missed opportunites to diagnose COPD from routinely collected patient data by reviewing patterns of health-care use and comorbidities present before diagnosis. We assessed patterns of health-care use in terms of lower respiratory consultations (infective and non-infective), lower respiratory consultations with a course of antibiotics or oral steroids, and chest radiography. If these events did not lead to a diagnosis of COPD, they were deemed to be missed opportunities. This study is registered with ClinicalTrials.gov, number NCT01655667. FINDINGS: We assessed data for 38,859 patients. Opportunities for diagnosis were missed in 32,900 (85%) of 38,859 patients in the 5 years immediately preceding diagnosis of COPD; in 12,856 (58%) of 22,286 in the 6-10 years before diagnosis, in 3943 (42%) of 9351 in the 11-15 years before diagnosis; and in 95 (8%) of 1167 in the 16-20 years before diagnosis. Between 1990 and 2009, we noted decreases in the age at diagnosis (0·05 years of age per year, 95% CI 0·03-0·07) and yearly frequency of lower respiratory prescribing consultations (rate ratio 0·982 opportunities per year, 95% CI 0·979-0·985). Prevalence of all comorbidities present at COPD diagnosis increased except for asthma and bronchiectasis, which decreased between 1990 and 2007, from 281 (33·4%) of 842 patients to 451 of 1465 (30·8%) for asthma, and from 53 of 842 (6·3%) to 53 of 1465 (3·6%) for bronchiectasis. In the 2 years before diagnosis, of 6897 patients who had had a chest radiography, only 2296 (33%) also had spirometry. INTERPRETATION: Opportunities to diagnose COPD at an earlier stage are being missed, and could be improved by case-finding in patients with lower respiratory tract symptoms and concordant long-term comorbidities. FUNDING: UK Department of Health, Research in Real Life.

The Small Magellanic Cloud (SMC) is well known to harbour a large number of high-mass X-ray binaries (HMXBs). The identification of their optical counterparts provides information on the nature of the donor stars and can help to constrain the parameters of these systems and their evolution. We obtained optical spectra for a number of HMXBs identified in previous Chandra and XMM-Newton surveys of the SMC using the AAOmega/2dF fibre-fed spectrograph at the Anglo-Australian Telescope. We find five new Be/X-ray binaries (BeXRBs; including a tentative one), by identifying the spectral type of their optical counterparts, and we confirm the spectral classification of an additional 15 known BeXRBs. We compared the spectral types, orbital periods and eccentricities of the BeXRB populations in the SMC and the Milky Way and we find marginal evidence for difference between the spectral type distributions, but no statistically significant differences for the orbital periods and the eccentricities. Moreover, our search revealed that the well-known supergiant B[e] star LHA 115-S 18 (or AzV 154) is associated with the weak X-ray source CXOU J005409.57-724143.5. We provide evidence that the supergiant star LHA 115-S 18 is the optical counterpart of the X-ray source, and we discuss different possibilities of the origin of its low X-ray luminosity (Lx ∼ 4 × 1033 erg s-1).

Solar proton flux measurements onboard Geostationary Operational Environmental Satellites (GOES) are of great importance as they cover several solar cycles, increasingly contributing to the development of long-term solar proton models and to operational purposes such as now-casting and forecasting of space weather. A novel approach for the cross calibration of GOES solar proton detectors is developed using as reference energetic solar proton flux measurements of NASA IMP-8 Goddard Medium Energy Experiment (GME). The spurious behavior in a part of IMP-8/GME measurements is reduced through the derivation of a nonlinear intercalibration function. The effective energy values of GOES solar proton detectors lead to a significant reduction of the uncertainties in spectra and may be used to refine existing scientific results, available models, and data products based on measurements over the last three decades. The methods presented herein are generic and may be used for calibration processes of other data sets as well.

Background: Panobinostat is a potent oral pan-deacetylase inhibitor that in preclinical studies has synergistic anti-myeloma activity when combined with bortezomib and dexamethasone. We aimed to compare panobinostat, bortezomib, and dexamethasone with placebo, bortezomib, and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma. Methods: PANORAMA1 is a multicentre, randomised, placebo-controlled, double-blind phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma who have received between one and three previous treatment regimens. Patients were randomly assigned (1:1) via an interactive web-based and voice response system, stratified by number of previous treatment lines and by previous use of bortezomib, to receive 21 day cycles of placebo or panobinostat (20 mg; on days 1, 3, 5, 8, 10, 12, orally), both in combination with bortezomib (1·3 mg/m2 on days 1, 4, 8, 11, intravenously) and dexamethasone (20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, orally). Patients, physicians, and the investigators who did the data analysis were masked to treatment allocation; crossover was not permitted. The primary endpoint was progression-free survival (in accordance with modified European Group for Blood and Marrow Transplantation criteria and based on investigators' assessment) and was analysed by intention to treat. The study is ongoing, but no longer recruiting, and is registered at ClinicalTrials.gov, number NCT01023308. Findings: 768 patients were enrolled between Jan 21, 2010, and Feb 29, 2012, with 387 randomly assigned to panobinostat, bortezomib, and dexamethasone and 381 to placebo, bortezomib, and dexamethasone. Median follow-up was 6·47 months (IQR 1·81-13·47) in the panobinostat group and 5·59 months (2·14-11·30) in the placebo group. Median progression-free survival was significantly longer in the panobinostat group than in the placebo group (11·99 months [95% CI 10·33-12·94] vs 8·08 months [7·56-9·23]; hazard ratio [HR] 0·63, 95% CI 0·52-0·76; p<0·0001). Overall survival data are not yet mature, although at the time of this analysis, median overall survival was 33·64 months (95% CI 31·34-not estimable) for the panobinostat group and 30·39 months (26·87-not estimable) for the placebo group (HR 0·87, 95% CI 0·69-1·10; p=0·26). The proportion of patients achieving an overall response did not differ between treatment groups (235 [60·7%, 95% CI 55·7-65·6] for panobinostat vs 208 [54·6%, 49·4-59·7] for placebo; p=0·09); however, the proportion of patients with a complete or near complete response was significantly higher in the panobinostat group than in the placebo group (107 [27·6%, 95% CI 23·2-32·4] vs 60 [15·7%, 12·2-19·8]; p=0·00006). Minimal responses were noted in 23 (6%) patients in the panobinostat group and in 42 (11%) in the placebo group. Median duration of response (partial response or better) was 13·14 months (95% CI 11·76-14·92) in the panobinostat group and 10·87 months (9·23-11·76) in the placebo group, and median time to response (partial response or better) was 1·51 months (1·41-1·64) in the panobinostat group and 2·00 months (1·61-2·79) in the placebo group. Serious adverse events were reported in 228 (60%) of 381 patients in the panobinostat group and 157 (42%) of 377 patients in the placebo group. Common grade 3-4 laboratory abnormalities and adverse events (irrespective of association with study drug) included thrombocytopenia (256 [67%] in the panobinostat group vs 118 [31%] in the placebo group), lymphopenia (202 [53%] vs 150 [40%]), diarrhoea (97 [26%] vs 30 [8%]), asthenia or fatigue (91 [24%] vs 45 [12%]), and peripheral neuropathy (67 [18%] vs 55 [15%]). Interpretation: Our results suggest that panobinostat could be a useful addition to the treatment armamentarium for patients with relapsed or relapsed and refractory multiple myeloma. Longer follow up will be necessary to determine whether there is any effect on overall survival. Funding: Novartis Pharmaceuticals. © 2014 Elsevier Ltd.

More than 10 years ago Haux et al. tried to answer the question how health care provision will look like in the year 2013. A follow-up workshop was held in Braunschweig, Germany, for 2 days in May, 2013, with 20 invited international experts in biomedical and health informatics. Among other things it had the objectives to discuss the suggested goals and measures of 2002 and how priorities on MI research in this context should be set from the viewpoint of today. The goals from 2002 are now as up-to-date as they were then. The experts stated that the three goals: "patient-centred recording and use of medical data for cooperative care"; "process-integrated decision support through current medical knowledge" and "comprehensive use of patient data for research and health care reporting" have not been reached yet and are still relevant. A new goal for ICT in health care should be the support of patient centred personalized (individual) medicine. MI as an academic discipline carries out research concerning tools that support health care professionals in their work. This research should be carried out without the pressure that it should lead to systems that are immediately and directly accepted in practice.

INTRODUCTION: The prevalence of drug resistance is approximately 10% in Europe and North America among newly infected patients. We aim to investigate the temporal patterns of resistance among drug naive HIV-infected individuals in Greece and also to determine transmission networking among those with resistant strains. MATERIALS AND METHODS: Protease (PR) and partial reverse transcriptase (RT) sequences were determined from 2499 newly diagnosed HIV-1 patients, in Greece, during 2003-2013. Genotypic drug resistance was estimated using the HIVdb: Genotypic Resistance Interpretation Algorithm. We identified transmission clusters of resistant strains on the basis of a large collection of HIV-1 sequences from 4024 seropositives in Greece. Phylodynamic analysis was performed using a Bayesian method. RESULTS: We estimated drug resistance levels among naïve patients on the basis of all resistance mutations in PR and partial RT. The overall prevalence of resistance was 19.6% (490/2499). Resistance to NNRTIs was the most common (397/2499, 15.9%) followed by PIs (116/2499, 4.6%) and NRTIs (79/2499, 3.2%). We found a significant trend for decreasing resistance to NRTIs over time (6.7%-1.6%). There was no time trend for the overall PI and NNRTI resistance. The most frequently observed major resistant sites in PR were V82 (2.0%) and L90 (1.8%). In RT, we found E138 (58.6%), K103 (13.1%), V179 (8.4%) and T215 (7.1%), M41 (4.7%) associated with resistance to NNRTIs and NRTIs, respectively. The prevalence of K103N and E138Q were significantly increased during 2003-2013. Crucially, we found that both K103N, E138Q are associated with transmission networking within men having sex with men (MSM) and intravenous drug user (IDU) local networks. The K103N network included seropositives across Greece, while the latter only from the recent IDU outbreak in Athens metropolitan area (1). Phylodynamic analyses revealed that the exponential growth for K103N network started in 2009 (Figure 1) and for the E138Q in 2010. CONCLUSIONS: The overall resistance has been stable in Greece over time; however, specific NNRTI resistance patterns are increasing. Notably, they are associated with local transmission networking, thus suggesting that this is the cause for the increased patterns of NNRTI resistance and not multiple transmissions of resistant strains from different sources among treated individuals. Our study highlights the advance of molecular epidemiology for understanding the dynamics of resistance.

BACKGROUND: In Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported. METHODS: HIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression. RESULTS: From the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more often from Western Europe origin, infected with subtype B virus, and recently infected (<1 year) (p<0.001). The prevalence of TDRM was highest in MSM (prevalence of 11.1%), followed by heterosexuals (6.6%) and IDU (5.1%, p<0.001). TDRM was predominantly ascribed to nucleoside reverse transcriptase inhibitors (NRTI) with a prevalence of 6.6% in MSM, 3.3% in heterosexuals and 2.0% in IDU (p = 0.001). A significant increase in resistance to non- nucleoside reverse transcriptase inhibitors (NNRTIs) and a decrease in resistance to protease inhibitors was observed in MSM (p = 0.008 and p = 0.006, respectively), but not in heterosexual patients (p = 0.68 and p = 0.14, respectively). CONCLUSIONS: MSM showed to have significantly higher TDRM prevalence compared to heterosexuals and IDU. The increasing NNRTI resistance in MSM is likely to negatively influence the therapy response of first-line therapy, as most include NNRTI drugs.

In this longitudinal study, we examined the extent to which perceived coach- and peer-created motivational climates are associated with athlete-group cohesion and satisfaction with participation among Spanish soccer players competing in the Third National Division. Multilevel modelling analyses showed that perceived coach-created task climate was positively related to perceived cohesion and players’ satisfaction with their participation within their team. Also, perceived peer-created task climate related positively to perceived cohesion. The results indicate the importance of considering peer-related aspects of the motivational climate in addition to considering the coach-related aspects of the motivational climate when examining motivational group dynamics in sport.

An 87 yr man was referred for abdominal pain over a pre-existing hernia in the right iliac fossa. Physical examination revealed a red painful palpable mass in the right lower abdominal quadrant. Abdominal CT scan revealed a loop of small intestine trapped into the abdominal wall. The patient underwent emergency laparotomy and the intraoperative findings consisted of a spigelian hernia, with perforation of the contained small intestine by a chicken bone (clavicle). The intestinal perforation was sutured and a polypropylene mesh plug and patch repair of the hernia was executed. The patient had an uneventful recovery and was discharged in stable condition. Our patient had a rare type of hernia with a rare complication. The arrow-shaped chicken bone led to irreducibility of the hernia and eventually to intestinal perforation. The diagnosis of spigelian hernias by history and physical examination is notoriously difficult. Recently, imaging modalities have increased preoperative diagnostic yield.

We show that a relatively sparse photonic crystal of high-permittivity magnetic garnet particles can induce a giant Faraday rotation of light transmitted through a finite slab of it. The underlying mechanism resides in wave propagation through collective Bloch modes, which are strongly localized in the particles.

BACKGROUND: In approximately 10% of newly diagnosed individuals in Europe, HIV-1 variants harboring transmitted drug resistance mutations (TDRM) are detected. For some TDRM it has been shown that they revert to wild type while other mutations persist in the absence of therapy. To understand the mechanisms explaining persistence we investigated the in vivo evolution of frequently transmitted HIV-1 variants and their impact on in vitro replicative capacity. RESULTS: We selected 31 individuals infected with HIV-1 harboring frequently observed TDRM such as M41L or K103N in reverse transcriptase (RT) or M46L in protease. In all these samples, polymorphisms at non-TDRM positions were present at baseline (median protease: 5, RT: 6). Extensive analysis of viral evolution of protease and RT demonstrated that the majority of TDRM (51/55) persisted for at least a year and even up to eight years in the plasma. During follow-up only limited selection of additional polymorphisms was observed (median: 1).To investigate the impact of frequently observed TDRM on the replication capacity, mutant viruses were constructed with the most frequently encountered TDRM as site-directed mutants in the genetic background of the lab strain HXB2. In addition, viruses containing patient-derived protease or RT harboring similar TDRM were made. The replicative capacity of all viral variants was determined by infecting peripheral blood mononuclear cells and subsequently monitoring virus replication. The majority of site-directed mutations (M46I/M46L in protease and M41L, M41L + T215Y and K103N in RT) decreased viral replicative capacity; only protease mutation L90M did not hamper viral replication. Interestingly, most patient-derived viruses had a higher in vitro replicative capacity than the corresponding site-directed mutant viruses. CONCLUSIONS: We demonstrate limited in vivo evolution of protease and RT harbouring frequently observed TDRM in the plasma. This is in line with the high in vitro replication capacity of patient-derived viruses harbouring TDRM compared to site-directed mutant viruses harbouring TDRM. As site-directed mutant viruses have a lower replication capacity than the patient-derived viruses with similar mutational patterns, we propose that (baseline) polymorphisms function as compensatory mutations improving viral replication capacity.

Atherosclerosis is the main cause of cardiovascular disease (CVD) and can lead to stroke, myocardial infarction, and death. The clinically available atheroprotective drugs aim mainly at reducing the levels of circulating low-density lipoprotein (LDL), increasing high-density lipoprotein (HDL), and attenuating inflammation. However, the cardiovascular risk remains high, along with morbidity, mortality, and incidence of adverse drug events. Pharmacogenomics is increasingly contributing towards the characterization of existing atheroprotective drugs, the evaluation of novel ones, and the identification of promising, unexplored therapeutic targets, at the global molecular pathway level. This chapter presents highlights of pharmacogenomics investigations and discoveries that have contributed towards the elucidation of pharmacological atheroprotection, while opening the way to new therapeutic approaches.

This work presents an investigation of the CO2 and N2 single and mixed gas phase permeability through supported ionic liquid membranes (SILMs) developed on ceramic nanoporous substrates with different pore size (1, 5 and 10 nm). ILs from the 1-alkyl-3-methylimidazolium tricyanomethanide family ([RMIM][TCM], with alkyl group, R: ethyl, butyl or octyl) were used as nanopore modifiers. These ILs exhibit high chemical and thermal stability, low viscosity and enhanced CO2 absorption capacity compared to other imidazolium based ILs. Thermal analysis of the developed SILMs unveiled a drastic liquid-to-solid transition upon confinement of the ILs into the pore channels with a size of 1 nm. The IL crystals formed inside these extremely small cavities possessed considerable thermal stability and underwent thermally induced phase transitions that differed significantly from those occurring in the unconfined bulk IL phase or in the IL phase when entrapped into the larger pore channels. The different physical state of the IL under confinement into the pores of different size resulted to significant variation of the flux properties between the developed SILM membranes. The effect of temperature on the CO2 permeability dependend strongly on the crystal thermal stability and microstructure dictated by the confinement into the nanopores. © 2014 Elsevier B.V. All rights reserved.

Background: Plasmablastic lymphoma (PBL) is a rare entity which is often causally related to infection by the Human Immunodeficiency Virus (HIV). Despite its predilection for oral cavity involvement, multiple cases of extra-oral involvement have been reported in the literature, more often among immunocompetent individuals. Case report: Herein we present the first case of primary PBL of the breast in an otherwise immunocompetent 36-year-old woman who was successfully treated with consolidation megatherapy and autologous stem cell transplantation. Conclusion: PBL carries a particularly poor prognosis and more intensive treatment is usually warranted. However, no treatment guidelines exist and treatment choices are made based on case reports and small retrospective case series. © 2014, International Institute of Anticancer Research. All rights reserved.

Purpose. The purpose of this paper is to present our technique for the treatment of periplate fractures. Methods. From 2009 to 2012 we treated three patients. In all cases the existing plate was left and the new one placed over the existing. Locking screws were placed through both plates. The other screws in the new plate were used as best suited the fracture. Results. In all cases less than 6 months had passed between fractures. None of the original fractures had healed. Mean followup was 2 years. All fractures proceeded to union within 7 months. No complications were recorded. All the patients returned to their normal activities and were satisfied with the results of their treatment. Conclusion. Our plate on plate technique is effective for the treatment of periplate fractures. A solid fusion can be achieved at the new fracture site without disturbing the previous fixation.

Platelet-rich plasma (PRP) is defined as an autologous concentrated preparation of platelets and their associated growth factors in a small volume of plasma. The presence of these growth factors has stimulated the scientific community to search about possible benefits of the use of PRP in tissue regeneration. Provided that previously in vitro and animal research demonstrated that PRP could probably play an important role in the treatment of neural tissue disorders, we aimed to review the current literature, regarding the clinical studies that have been conducted to confirm this hypothesis. More specifically, we have reviewed the literature concerning the clinical application of PRP in peripheral neuropathies and investigated if there is strong evidence to establish the use of PRP in clinical practice as a therapeutic option. In contrast with animal studies, we have been able to identify only few clinical data concerning the use of PRP in peripheral neuropathies. We found five trials matched to our research that yields positive and promising results for the future for the application of PRP for the therapy of disorders of the peripheral nervous system. It is obvious that this interesting field of research gives to the scientists the ability to expand it extensively, in terms of both quality and quantity.

Manifold advantages are foreseen by using carbon nanotubes (CNTs) as support for inorganic TiO2 nanoparticles due to the unique texture/morphology and adsorption capacity of CNTs. Synergistic effects might also result from interfacial charge transfer between the CNTs and TiO2. Effective charge transfer has the potentiality to limit electron/hole recombination and shift the TiO2 photocatalytic response to the visible range. Homogeneous mixing and intimate contact between the graphitic and TiO2 surfaces are of high importance in order to trigger synergistic effects. Thus, the existence of complementary methods to shed light on both these features is of high importance when developing TiO2/CNT composite photocatalysts. In this work, a wide variety of TiO2/CNT composites was prepared by a simple hydration/dehydration procedure, using single-wall (SWCNTs) and multi-wall (MWCNTs) carbon nanotubes, either functionalized or not, and TiO2 nanoparticles of different size. To evaluate the degree of homogeneity between the graphitic and inorganic phases, a new methodology which was based on a complex interpretation of the liquid nitrogen porosimetry (LN2) isotherms of the composites and of each phase in the composite separately was developed. Furthermore, interface interaction characteristics were elucidated by micro-Raman spectroscopy while small-angle X-ray scattering (SAXS) measurements provided insight on the surface roughness and micropore structure of the TiO2/SWCNT samples. The Raman analysis concluded to the absence of any interfacial interaction. In this context the efficiency of the prepared composites to photocatalytically oxidize caffeine was evaluated in regard to their homogeneity, as derived by the LN2 method. As expected, in the absence of synergetic effects the photocatalytic efficiency correlated well with the extent of mixing between the CNTs and TiO2 phases. The discrepancy observed for one of the samples was attributed to the existence of large micropores, a feature that was distinguishable solely by SAXS measurements. © 2013 Elsevier B.V.

Herein we report on enhanced organic solar cell performance through the incorporation of cathode interfacial layers consisting of self-organized porphyrin nanostructures with a face-on configuration. In particular, a water/methanol-soluble porphyrin molecule, the free base meso-tetrakis(1- methylpyridinium-4-yl)porphyrin chloride, is employed as a novel cathode interlayer in bulk heterojunction organic photovoltaics. It is demonstrated that the self-organization of this porphyrin compound into aggregates in which molecules adopt a face-to-face orientation parallel to the organic semiconducting substrate induces a large local interfacial electric field that results in a significant enhancement of exciton dissociation. Consequently, enhanced photocurrent and open circuit voltage were obtained resulting in overall device efficiency improvement in organic photovoltaics based on bulk heterojunction mixtures of different polymeric donors and fullerene acceptors, regardless of the specific combination of donor-acceptor employed. To highlight the impact of molecular orientation a second porphyrin compound, the Zn-metallated meso-tetrakis(1-methylpyridinium-4-yl)porphyrin chloride, was also studied and it was found that it forms aggregates with an edge-to-edge molecular configuration inducing a smaller increase in the device performance. © The Royal Society of Chemistry.

AIM: Posterior cervical spine fixation has undergone tremendous advancement in recent years. The purpose of this study is to present our experience with the Roy-Camille instrumentation for posterior cervical stabilization after injury in a long-term follow-up. PATIENTS AND METHODS: From 1985 to 1995, 76 patients with a lower cervical spine traumatic lesion were treated in a single institution by posterior plate stabilization using the Roy-Camille plates (R-C plates). Fifty-four men and 22 women with a mean age of 43.2 years were involved. In 59 patients the injuries were due to a road traffic accident, in 14 cases the fall from a high was responsible, while in two cases the injuries were due to sport activities. There were four bilateral dislocations, nine unilateral dislocations, 56 fracture dislocations, five fracture separations of a lateral mass and two burst fractures. Neurological lesions were present in 65 patients (9 ASIA A, 16 ASIA B, 22 ASIA C, 18 ASIA D and 11 ASIA E). All patients had minimum follow-up of 7 years. Fifty-nine patients were followed up for a mean period of 21 years (14-27 years). RESULTS: Stability was obtained in all but two cases. Reoperation was done in two cases: in one for the correction of the lost reduction and in a second for the reinsertion of a screw irritating a nerve root. No case in the ASIA A group showed neurological improvement, a fact observed in the other groups. CONCLUSIONS: The R-C plates were used in the last quarter of the last century. This technique showed good short-time results, and we have shown good results in a long-term follow-up as well. The literature referred to this technique was favorable, as far as the biomechanical behavior and also clinical application concern. The question about this plating system abundance still remains unanswered.

© 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. (S.M. Creighton). Objective: In 2001, this team published an observational study of the clinical outcomes of a cohort of adolescent girls born with ambiguous genitalia. The poor outcomes observed represented a major scientific challenge to the standard practice of childhood feminising genital surgery. That publication was one of several contributing to a call for change in surgical practice, which culminated in the publication of the Chicago Consensus Document in 2006. The aim of this current study was to repeat the same evaluation of clinical outcomes on a recent cohort of adolescent girls and compare the two cohorts to identify differences in adolescent outcomes which may indicate a change in paediatric surgical practice. Methods: This was an observational study of a current cohort of adolescent girls treated in childhood for ambiguous genitalia and referred to a specialist adolescent disorders of sex development (DSD) service for assessment. Data were collected on surgical history, genital examination findings and treatment recommendations for 30 consecutive adolescents over a 5-year period. Findings were compared with those of a similar cohort of adolescent girls published over a decade previously. Results: Clitoral surgery remained common (93{%} vs 100{%}, current cohort vs historical cohort). However, concomitant vaginoplasty was performed less frequently (80 vs 100{%} current vs historical). Vaginoplasty revision surgery was also less commonly required (65 vs 81{%}), although 24{%} of the recent cohort still required major revision surgery prior to intercourse. There was some improvement to the cosmetic outcomes as deemed by the surgical team using the same criteria as the previous report. Conclusions: This study provides someslight evidence of recent practice change.Therewas asmall reduction in the number of vaginoplasties performed in childhood and an improvement in vaginoplasty outcomes and cosmesis.However, therewas no identifiable change inmanagement of clitoromegaly and the numbers of clitoral reduction operations remained high. This is surprising given the clear evidence of a detrimental impact of surgery on clitoral sensation and sexual function.

The article discusses the significance of on-the-spot observation and eye witnessing as powerfulscientific tools for establishing the real in the early sixteenth century. In particular, I argue that thesimulation of such tools in the paratextual material to Utopia, especially the prefatory/postscriptletters, enhance, preemptively, the verisimilitude of the Utopian society as well as the materialityof the island at hand. If eye witnessing is reality-conferring, then, the powerful Renaissance actof reading a text as a simulation of eye witnessing is reality-conferring too. In this light, to readUtopia through the paratextual letters is to place one’s trust in the literal existence of Utopia insofaras reading simulates the act of seeing with one’s own eyes and bearing witness to a palpable reality.Keywords: Eye Witnessing, Humanism, Paratext, Utopia, Verisimilitude1. Paratext, Utopia and LiminalityNearly five hundred years after its first publication in 1516, Thomas More’sUtopia continues to spark endless discussions in relation to its potentialmeanings or its exact nature.1 More could not have written Utopia at a bettertime. As Alistair Fox maintains, when he sat down to write it in 1515, ‘Hisimagination had been excited by the discoveries of Cabot and Vespucci in theNew World… the momentum of Erasmian reform was approaching its height;and he had the stimulating company… of Cuthbert Tunstal, Busleyden andPeter Giles, humanists with interests and ambitions similar to his own’ (1984,53). The publication of Utopia was accompanied by paratextual material (attimes called parerga) – maps, illustrations, verses as well as a number of letterswritten by friends or acquaintances from the wider humanist continentalcircles. By fervently supporting the project, this paratextual material – whichwas altered to a great degree from edition to edition, thus also constantlyreshaping readers’ reception of Utopia – worked towards legitimising More’sendeavour, establishing its truthfulness, and announcing beforehand its acceptanceby early sixteenth-century readership.2‘Paratext’ in literature covers everything that lies around a text. GérardGenette has famously called paratext ‘a zone between text and off-text, a zonenot only of transition but also of transaction’ between the author(s) and thepublic, or ‘the most socialized side of the practice of literature’ (1997, 1, 14).

Suppression of uninvolved immunoglobulins is common in multiple myeloma (MM) but the prognostic significance of this phenomenon has not been assessed. We evaluated the prognostic significance of the preservation of uninvolved immunoglobulins in 1755 consecutive, unselected, patients with newly diagnosed, symptomatic MM with pre-therapy immunoglobulin levels measured by nephelometry. Suppression of at least one uninvolved immunoglobulin was observed in 87% of patients and was more common in patients with immunoglobulin A myeloma, those aged over 65 years, in patients with advanced-International Staging System (ISS) stage, extensive-bone marrow infiltration, anemia, low platelet counts, high levels of serum M-monoclonal protein or renal dysfunction. Patients with preserved immunoglobulins had a better survival than patients with suppressed immunoglobulins (median survival 55 vs 41.5 months, P<0.001). In multivariate analysis, preservation of uninvolved immunoglobulins was independently associated with better survival (hazard ratio: 0.781, 95% confidence interval: 0.618-0.987, P=0.039); irrespective of the treatment. In a subset of 500 patients, which were strictly followed for disease progression, preservation of uninvolved immunoglobulins was associated with a significantly longer progression-free survival (60 vs 25 months, P<0.001), independently of other common prognostic factors. In conclusion, preservation of uninvolved immunoglobulins in newly diagnosed patients with symptomatic MM was independently associated with long term disease control and improved survival. © 2014 Macmillan Publishers Limited. All rights reserved.

Allergy to cow's milk, egg, wheat, soy, peanut, tree nuts, fish, and shellfish constitutes the majority of food allergy reactions, but reliable estimates of their prevalence are lacking. This systematic review aimed to provide up-to-date estimates of their prevalence in Europe.Studies published in Europe from January 1, 2000, to September 30, 2012, were identified from searches of four electronic databases. Two independent reviewers appraised the studies and extracted the estimates of interest. Data were pooled using random-effects meta-analyses. Fifty studies were included in a narrative synthesis and 42 studies in the meta-analyses. Although there were significant heterogeneity between the studies, the overall pooled estimates for all age groups of self-reported lifetime prevalence of allergy to cow's milk, egg, wheat, soy, peanut, tree nuts, fish, and shellfish were 6.0% (95% confidence interval: 5.7-6.4), 2.5% (2.3-2.7), 3.6% (3.0-4.2), 0.4% (0.3-0.6), 1.3% (1.2-1.5), 2.2% (1.8-2.5), and 1.3% (0.9-1.7), respectively. The prevalence of food-challenge-defined allergy to cow's milk, egg, wheat, soy, peanut, tree nuts, fish, and shellfish was 0.6% (0.5-0.8), 0.2% (0.2-0.3), 0.1% (0.01-0.2), 0.3% (0.1-0.4), 0.2% (0.2-0.3), 0.5% (0.08-0.8), 0.1% (0.02-0.2), and 0.1% (0.06-0.3), respectively. Allergy to cow's milk and egg was more common among younger children, while allergy to peanut, tree nuts, fish, and shellfish was more common among the older ones. There were insufficient data to compare the estimates of soy and wheat allergy between the age groups. Allergy to most foods, except soy and peanut, appeared to be more common in Northern Europe. In summary, the lifetime self-reported prevalence of allergy to common foods in Europe ranged from 0.1 to 6.0%. The heterogeneity between studies was high, and participation rates varied across studies reaching as low as <20% in some studies. Standardizing the methods of assessment of food allergies and initiating strategies to increase participation will advance this evidence base.

BACKGROUND: Little is known of the extent to which nursing-care tasks are left undone as an international phenomenon. AIM: The aim of this study is to describe the prevalence and patterns of nursing care left undone across European hospitals and explore its associations with nurse-related organisational factors. METHODS: Data were collected from 33 659 nurses in 488 hospitals across 12 European countries for a large multicountry cross-sectional study. RESULTS: Across European hospitals, the most frequent nursing care activities left undone included 'Comfort/talk with patients' (53%), 'Developing or updating nursing care plans/care pathways' (42%) and 'Educating patients and families' (41%). In hospitals with more favourable work environments (B=-2.19; p<0.0001), lower patient to nurse ratios (B=0.09; p<0.0001), and lower proportions of nurses carrying out non-nursing tasks frequently (B=2.18; p<0.0001), fewer nurses reported leaving nursing care undone. CONCLUSIONS: Nursing care left undone was prevalent across all European countries and was associated with nurse-related organisational factors. We discovered similar patterns of nursing care left undone across a cross-section of European hospitals, suggesting that nurses develop informal task hierarchies to facilitate important patient-care decisions. Further research on the impact of nursing care left undone for patient outcomes and nurse well-being is required.

The aim of the present study is to investigate the morphodynamic regime of the coastal area of Xylokastro (north coast of Peloponnese), in order to identify and evaluate the processes controlling its formation and evolution. Within this concept, a number of factors have been considered and evaluated; near-shore morphometry and granulometry along shore-normal profiles, the direction and potential volumes of long- and cross-shore sediment transport the decadal and future trends of coastline displacement, the available information for terrestrial sediment influx and the geological processes operating in the broader coastal region of Xylokastro (i.e. subaqueous slides) as well as human interference. On the basis of these results, the formation and evolution of this coastal stretch seems to be governed primarily by the neotectonic activity and relative change of sea level rise, and secondarily by the wave-induced near-shore sediment transport; the role of the latter could be enhanced substantially by human intervention (i.e. construction of marina, seafront walls). Moreover, the expected eustatic increase in sea level by the year 2100, could cause a coastline retreat up to 9 m (SLR=0.38 m) or >19 m (SLR≥1 m).

Angiogenesis has been implicated in ovarian cancer pathogenesis. Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, has recently been incorporated in ovarian cancer treatment in combination with chemotherapy both in a frontline setting and in disease recurrence. However, resistance eventually develops and treatment with bevacizumab is associated with increased risk for toxicities such as thromboembolic and hemorrhagic events, gastrointestinal perforation, and impaired wound healing, suggesting the need for new therapeutic approaches. Targeting of the angiopoietins/Tie2 pathway has gained accumulating interest during the last few years as a strategy to overcome bevacizumab resistance and toxicities. Trebananib is a first-in-class peptibody that inhibits angiopoietin 1 and 2 interaction with their receptor Tie2. The molecular profile of this agent, the preclinical data, and clinical studies demonstrating its efficacy in ovarian cancer are discussed in this review. © 2014 Liontos et al.

In recent decades, there has been an increasing interest in the prognosis of maximum surface ozone concentrations due to the adverse effects on human health, animal population, agricultural productivity and forestry. The present study deals with the development and application of Artificial Neural Network (ANN) models in predicting the maximum daily surface ozone concentration in several locations within the greater Athens area (GAA), 24-hours in advance. Meteorological and air pollution data during the period 2001 to 2005 were provided by the network of the Hellenic Ministry of the Environment, Energy and Climate Change. Hourly values of barometric pressure and total solar irradiance for the same period have been recorded by the National Observatory of Athens. A training data set for the ANN prognostic model was generated by employing the superposed epoch analysis.The evaluation of the performance of the developed model, using appropriate statistical indices, clearly indicates that the risk of surface ozone values exceeding the European Union (EU) threshold for human health protection can be successfully predicted. This suggests that the proposed ANN model can be used to issue warnings for the general public and especially certain sensitive groups of the population. © 2014 Global NEST Printed in Greece. All rights reserved.

In our multicenter retrospective analysis in 186 patients with metastatic renal cell carcinoma (mRCC) and synchronous metastases treated with sunitinib, we examined the role of cytoreductive nephrectomy (CN) in this clinical setting. CN proved to have a beneficial prognostic effect in survival independent of other diseaseor patient-related factors. CN remains a reasonable option for mRCC patients scheduled to be treated with vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs). Introduction/Background: The aim of this study was to evaluate the prognostic role of CN in patients with mRCC and synchronous metastases treated with the VEGF receptor TKI, sunitinib. Patients and Methods: Patients with a diagnosis of metastases before, at the time of, or within 3 months from the diagnosis of renal cell carcinoma (RCC) and first-line treatment with sunitinib were included. Baseline characteristics were correlated with overall survival (OS) according to hazard ratios estimated from univariate Cox proportional hazards models. Significant factors were then included in a multivariate Cox proportional hazards model. Results: One hundred eighty-six patients treated between January 2006 and March 2012 were selected. Thirty-six (19%) had not undergone CN. CN was offered to younger patients with better prognoses. Patients who underwent CN lived significantly longer than patients without CN (median OS, 23.9 [95% confidence interval (CI), 20.8-28.8] vs. 9 [95% CI, 4-16.4] months; P < .001). Multivariate analysis showed that CN had an independent prognostic significance. No specific subgroup benefiting from CN was identified. Conclusion: CN was an independent favorable prognostic factor in patients with synchronous metastases from RCC, treated with sunitinib. Information regarding the selection of mRCC patients likely to benefit from CN might be derived by ongoing phase III trials. © 2014 Elsevier Inc. All rights reserved.

The molecular pathways implicated in multiple myeloma (MM) development are rather unknown. We studied epigenetic and DNA damage response (DDR) signals at selected model loci (N-ras, p53, d-globin) in bone marrow plasma cells and peripheral blood mononuclear cells (PBMCs) from patients with monoclonal gammopathy of undetermined significance (MGUS; n=20), smoldering/asymptomatic MM (SMM; n=29) and MM (n=18), as well as in healthy control-derived PBMCs (n=20). In both tissues analyzed, a progressive, significant increase in the looseness of local chromatin structure, gene expression levels and DNA repair efficiency from MGUS to SMM and finally to MM was observed (all P<0.002). Following ex vivo treatment with melphalan, a gradual suppression of the apoptotic pathway occurred in samples collected at different stages of myelomagenesis, with the severity and duration of the inhibition of RNA synthesis, p53 phosphorylation at serine15 and induction of apoptosis being higher in MGUS than SMM and lowest in MM patients (all P<0.0103). Interestingly, for all endpoints analyzed, a strong correlation between plasma cells and corresponding PBMCs was observed (all P<0.0003). We conclude that progressive changes in chromatin structure, transcriptional activity and DDR pathways during myelomagenesis occur in malignant plasma cells and that these changes are also reflected in PBMCs. © 2014 Macmillan Publishers Limited. All rights reserved.

AIM: The bacterial and atypical etiology of acute exacerbations of chronic obstructive pulmonary disease was investigated and the diagnostic techniques used were compared among 92 hospitalized patients. MATERIALS & METHODS: Sputum specimens were investigated using culture and PCR, serological status evaluation was performed and the inflammatory profile was associated with the microbiological results. RESULTS & CONCLUSION: The majority of the patients (65.2%) had very severe airway obstruction. The most common bacteria were Haemophilus influenzae and Pseudomonas aeruginosa (23.9 and 14.1%, respectively). Acinetobacter baumannii- and P. aeruginosa-positive cultures were associated with prolonged hospitalization and severe airway obstruction (p = 0.03 and 0.031, respectively). Chlamydia pneumoniae or Mycoplasma pneumoniae infection was diagnosed in four and two patients, respectively. Discrepant results were detected between PCR and serology, especially regarding C. pneumoniae.

A highly efficient hybrid photocatalytic/ultrafiltration process is demonstrated for water purification using visible light. The process relies on the development of partially reduced graphene oxide/TiO2 composite membranes and their incorporation into an innovative water purification device that combines membrane filtration with semiconductor photocatalysis. Composites consisting of graphene oxide sheets decorated with TiO2 nanoparticles were deposited and stabilized into the pores of ultrafiltration mono-channel monoliths using the dip-coating technique. Cross-flow and dead-end filtration experiments were sequentially conducted in dark, under UV and visible light. The membrane surface was irradiated for the elimination of two synthetic azo-dyes, methyl orange and methylene blue, from water solutions. The synergetic effects of graphene oxide on pollutant adsorption and photocatalytic degradation capacity of TiO2 were thoroughly studied, while the influence of the pore size of the monolithic substrate on the deposition morphologies was also elucidated. Moreover, the performance of the novel hybrid process was compared with that of standard nanofiltration with respect to pollutant removal efficiency and energy consumption, providing firm evidence for its economic feasibility and efficiency. © 2014 Elsevier B.V.

In the present paper I argue that, since Cyprus came under the British rule and for at least seven decades, Britain did not consider Cyprus a “territory of major strategic importance for the Crown”. I also argue that the policy makers of colonial Britain probably considered this island one of the “poor colonies”, since it did not have raw material deposits or any kind of industrial infrastructure. Thus, I suggest that Greek researchers should examine how Great Britain was perceiving the strategic importance of Cyprus until the end of World War II and, therefore, should not insist on blaming the Greek side that, supposedly, did not take into account Britain’s sensitivity and “unwisely sought the Union (Enosis) of Cyprus with Greece, which annoyed Britain and led to the well-known traumatic events”.

OBJECTIVE: Recent evidence suggests that climacteric symptoms may be intensified by specific temperament and personality traits in postmenopausal women. In this study we investigate Cloninger's model of personality in relation to menopausal symptoms. METHODS: One-hundred and seventy peri- and postmenopausal women consecutively recruited from a menopause clinic of an academic hospital completed the Cloninger's Temperament and Character Inventory (TCI-140) which measures four dimensions of temperament: Harm avoidance, Novelty seeking, Reward dependence and Persistence, as well as three dimensions of character: Self-directedness, Cooperativeness, and Self-transcendence. Menopausal somatic, vasomotor and psychological symptoms were also assessed using the Greene Climacteric Scale. RESULTS: In comparison to the norms of the Greek general population, postmenopausal women presented lower scores in Novelty seeking and Reward dependence and higher scores in Persistence, Self-directedness, Cooperativeness and Self-transcendence. Higher harm avoidance (the inclination to avoid potential punishment, be shy and fearful of uncertainty) significantly correlated with anxiety and depressive symptoms while lower Self-directedness (the ability to have the willpower to adapt to or overcome any changes) correlated with depressive symptoms only. By multivariate regression analysis, higher Harm avoidance and lower Self-directedness were independently associated with the presence of depressive symptoms. No significant associations were observed between TCI-140 traits and somatic or vasomotor symptoms. CONCLUSIONS: Our findings indicate that most temperament and character traits according to Cloninger's model in peri- and postmenopausal women varied significantly as compared to the general population. Among several traits, high Harm avoidance and low Self-directedness were most strongly associated with psychological climacteric distress but not with somatic and vasomotor symptoms.

Objective Recent evidence suggests that climacteric symptoms may be intensified by specific temperament and personality traits in postmenopausal women. In this study we investigate Cloninger's model of personality in relation to menopausal symptoms. Methods One-hundred and seventy peri- and postmenopausal women consecutively recruited from a menopause clinic of an academic hospital completed the Cloninger's Temperament and Character Inventory (TCI-140) which measures four dimensions of temperament: Harm avoidance, Novelty seeking, Reward dependence and Persistence, as well as three dimensions of character: Self-directedness, Cooperativeness, and Self-transcendence. Menopausal somatic, vasomotor and psychological symptoms were also assessed using the Greene Climacteric Scale. Results In comparison to the norms of the Greek general population, postmenopausal women presented lower scores in Novelty seeking and Reward dependence and higher scores in Persistence, Self-directedness, Cooperativeness and Self-transcendence. Higher harm avoidance (the inclination to avoid potential punishment, be shy and fearful of uncertainty) significantly correlated with anxiety and depressive symptoms while lower Self-directedness (the ability to have the willpower to adapt to or overcome any changes) correlated with depressive symptoms only. By multivariate regression analysis, higher Harm avoidance and lower Self-directedness were independently associated with the presence of depressive symptoms. No significant associations were observed between TCI-140 traits and somatic or vasomotor symptoms. Conclusions Our findings indicate that most temperament and character traits according to Cloninger's model in peri- and postmenopausal women varied significantly as compared to the general population. Among several traits, high Harm avoidance and low Self-directedness were most strongly associated with psychological climacteric distress but not with somatic and vasomotor symptoms. © 2014 International Menopause Society.

Depression and anxiety, the most common mental disorders (CMD), are highly prevalent among women of childbearing age, but are even higher among mothers in low- and middle-income countries (LMIC), possibly due to mothers' disproportionate exposure to multiple risk factors, such as poverty, gender disparities and violence, and a high prevalence of medical illness. The extra burden imposed by maternal CMD in LMIC can be nothing short of catastrophic, affecting infant and child growth and leading to preventable illness and death among children. One possible mechanism, by which maternal CMD lead to compromised child development, is through negatively affecting mothers' health-promoting behaviors (e.g., contraceptive use, participation in antenatal care) and child-care practices (e.g., vaccination uptake, cessation of breastfeeding, sanitation practices). The aim of this study was three-fold. First, to assess psychological distress among mothers of young children (aged 0-5 years) as measured by the Kessler 6 (K6), a brief screening instrument for nonspecific psychological distress in Ghana and Uganda. Second, to identify sociodemographic, socioeconomic, obstetric, and psychosocial correlates of maternal psychological distress in Ghana and Uganda. Third, to explore the relationship between maternal psychological distress, child health-promoting practices, and child health outcomes and nutritional status. The study utilized cross-sectional baseline data from the Millennium Villages Project. One hundred mothers in Ghana and 100 in Uganda who had at least one child up to 5 years at the time of baseline collection participated in the study. Results provided evidence for the adequate reliability and validity of the K6 in our study. Several correlates of maternal distress were identified in the study, some of which were common for both sites, while others where site-specific. Maternal distress was associated with maternal sanitation practices in Uganda. An exploratory analysis revealed a significant relationship between maternal distress and risk for child undernutrition. These findings offer partial support for the relationship between maternal psychological distress and poor child health outcomes. Discussion of the study findings focuses on the social roots of maternal distress in SSA. The clinical implications of the study and recommendations for future research are discussed.

The purine utilization pathway has been thoroughly characterized in Aspergillus nidulans. We establish here the subcellular distribution of seven key intracellular enzymes, xanthine dehydrogenase (HxA), urate oxidase (UaZ), 5-hydroxy-isourate hydrolase (UaX), 2-oxo-4-hydroxy-4-carboxy ureido imidazoline decarboxylase (UaW), allantoinase (AlX), allantoicase (AaX), ureidoglycolate lyase (UglA), and the fungal specific a-ketoglutarate Fe(II)-dependent dioxygenase (XanA). HxA, AlX, AaX, UaW and XanA are cytosolic, while UaZ, UaX and UglA are peroxisomal. Peroxisomal localization was confirmed by using appropriate pex mutants. The pathway is largely, but not completely conserved in the Eurotiomycetes, noticeably in some species AaX is substituted by an alternative enzyme of probable bacterial origin. UaZ and the urate–xanthine UapA and UapC transporters, are also localized in specific cells of the conidiophore. We show that metabolic accumulation of uric acid occurring in uaZ null mutations is associated with an increased frequency of appearance of morphologically distinct colony sectors, diminished conidiospore production, UV resistance and an altered response to oxidation stress, which may provide a rationale for the conidiophore-specific localization. The pathway-specific transcription factor UaY is localized in both the cytoplasm and nuclei under non-inducing conditions, but it rapidly accumulates exclusively to the nuclei upon induction by uric acid.

The aim of this paper is to present in a useful and understandable way how climatic change could be interpreted for tourism and recreation. Future climate change conditions are analyzed using the Climate Version of the Local Model (CLM) based on the COSMO model, which is currently used-among other weather services-by the DWD (Deutscher Wetterdienst) for operational weather forecast. The climate simulations concern the future periods 2021-2050 and 2071-2100 against the reference period 1961-1990, under A1B scenario. Based on regional climate simulations, the analysis for tourism can be performed using the Climate-Tourism-Information-Scheme (CTIS). The CTIS contains detailed climate information, which can be used by tourists to anticipate thermal comfort, aesthetical and physical conditions for planning their vacations. Furthermore, the Physiologically Equivalent Temperature (PET), which is one of the most popular physiological thermal indices derived from the human energy balance, is used in the analysis in order to describe the effect of climate. The future simulations concerning PET and CTIS for the area for Athens have been exemplary used, in order to consider them for tourism industry and local authorities for tourism planning. © 2014 Global NEST Printed in Greece. All rights reserved.

A series of methodologies are described in this paper aiming to quantify the natural hazard due to the coastal changes at a deltaic fan. The coastline of Istiaia (North Evia, Greece) has been chosen for this study as several areas of accretion and erosion have been identified during the past few decades. We combined different types of datasets, extracted from high resolution panchromatic aerial photographs and traced the contemporary shoreline by high accuracy surveying with Real Time Kinematics (RTK) GPS equipment. The interpretation of all shorelines required geo-statistical analysis in a Geographical Information System. A large number of high resolution morphological sections were constructed normally to the coast, revealing erosional and depositional parts of the beach. Retreating and extension rates were calculated for each section reaching the values of 0.98 m/yr and 1.36 m/yr, respectively. The results proved to be very accurate, allowing us to expand the developed methodology by using more complete time-series of remote sensing datasets along with more frequent RTK-GPS surveying.

A previously developed method for measurement of oleocanthal and oleacein in olive oil by quantitative 1H NMR was expanded to include the measurement of the monoaldehydic forms of oleuropein and ligstroside aglycons. The method was validated and applied to the study of 340 monovarietal Greek and Californian olive oils from 23 varieties and for a 3-year period. A wide variation concerning the concentrations of all four secoiridoids was recorded. The concentration of each one ranged from nondetectable to 711 mg/kg and the sum of the four major secoiridoids (named as D3) ranged from nondetectable to 1534 mg/kg. Examination of the NMR profile of the olive oil extract before and after contact with normal or reversed stationary chromatography phase proved the artificial formation of the 5S,8S,9S aldehydic forms of oleuropein and ligstroside aglycon isomers during chromatography. Finally, methyl elenolate was identified for the first time as a minor constituent of olive oil. © 2014 American Chemical Society.

A previously developed method for measurement of oleocanthal and oleacein in olive oil by quantitative (1)H NMR was expanded to include the measurement of the monoaldehydic forms of oleuropein and ligstroside aglycons. The method was validated and applied to the study of 340 monovarietal Greek and Californian olive oils from 23 varieties and for a 3-year period. A wide variation concerning the concentrations of all four secoiridoids was recorded. The concentration of each one ranged from nondetectable to 711 mg/kg and the sum of the four major secoiridoids (named as D3) ranged from nondetectable to 1534 mg/kg. Examination of the NMR profile of the olive oil extract before and after contact with normal or reversed stationary chromatography phase proved the artificial formation of the 5S,8S,9S aldehydic forms of oleuropein and ligstroside aglycon isomers during chromatography. Finally, methyl elenolate was identified for the first time as a minor constituent of olive oil.

A previously developed method for measurement of oleocanthal and oleacein in olive oil by quantitative 1H NMR was expanded to include the measurement of the monoaldehydic forms of oleuropein and ligstroside aglycons. The method was validated and applied to the study of 340 monovarietal Greek and Californian olive oils from 23 varieties and for a 3-year period. A wide variation concerning the concentrations of all four secoiridoids was recorded. The concentration of each one ranged from nondetectable to 711 mg/kg and the sum of the four major secoiridoids (named as D3) ranged from nondetectable to 1534 mg/ kg. Examination of the NMR profile of the olive oil extract before and after contact with normal or reversed stationary chromatography phase proved the artificial formation of the 5S,8S,9S aldehydic forms of oleuropein and ligstroside aglycon isomers during chromatography. Finally, methyl elenolate was identified for the first time as a minor constituent of olive oil.

Electrons mediate many of the interactions between atoms in a solid. Their propagation in a material determines its thermal, electrical, optical, magnetic and transport properties. Therefore, the constant energy contours characterizing the electrons, in particular the Fermi surface, have a prime impact on the behaviour of materials. If anisotropic, the contours induce strong directional dependence at the nanoscale in the Friedel oscillations surrounding impurities. Here we report on giant anisotropic charge density oscillations focused along specific directions with strong spin-filtering after scattering at an oxygen impurity embedded in the surface of a ferromagnetic thin film of Fe grown on W(001). Utilizing density functional theory, we demonstrate that by changing the thickness of the Fe films, we control quantum well states confined to two dimensions that manifest as multiple flat energy contours, impinging and tuning the strength of the induced charge oscillations which allow to detect the oxygen impurity at large distances (approximate to 50 nm).

Purpose; Hepatic resection is the mainstay of the curative treatment of primary hepatic tumors, with constantly improving short and long term results. Radiofrequency ablation (RFA)-assisted liver resection is a relatively new method of transection of the liver parenchyma with favorable intra- and perioperative results. The aim of this study was to investigate the oncological efficacy (long term overall survival/OS and disease free survival/DFS) and to confirm the favorable short term morbidity and mortality. Methods: Between May 2004 and January 2007, 28 patients underwent 32 resections with removal of 50 hepatocellular carcinoma (HCC) lesions. The technique of parenchymal transection has been described previously as RFA-assisted liver resection. Results: Thirty-day morbidity and mortality were 42.8 and 0%, respectively. Blood transfusion was necessary for 28.5% of the patients. The median hospital stay was 16.5 days (range 5-34). The 1- and 3-year OS were 92.9 and 65.7%, respectively. The 1- and 3-year DFS were 62.3 and 54.6% respectively. No patient developed metastatic disease or local recurrence at the margin site. Twelve patients (42.9%) developed in-the-liver recurrence away from the resection area. Conclusion: RFA-assisted liver resection is a safe and oncologically efficacious method for the surgical treatment of HCC with results comparable to other surgical techniques.

We construct and analyze a model of the relativistic steady-state magnetohydrodynamic rarefaction that is induced when a planar symmetric flow (with one ignorable Cartesian coordinate) propagates under a steep drop of the external pressure profile. Using the method of self-similarity, we derive a system of ordinary differential equations that describe the flow dynamics. In the specific limit of an initially homogeneous flow, we also provide analytical results and accurate scaling laws. We consider that limit as a generalization of the previous Newtonian and hydrodynamic solutions already present in the literature. The model includes magnetic field and bulk flow speed having all components, whose role is explored with a parametric study.

We construct and analyze a model of the relativistic steady-state magnetohydrodynamic rarefaction that is induced when a planar symmetric flow (with one ignorable Cartesian coordinate) propagates under a steep drop of the external pressure profile. Using the method of self-similarity, we derive a system of ordinary differential equations that describe the flow dynamics. In the specific limit of an initially homogeneous flow, we also provide analytical results and accurate scaling laws. We consider that limit as a generalization of the previous Newtonian and hydrodynamic solutions already present in the literature. The model includes magnetic field and bulk flow speed having all components, whose role is explored with a parametric study.

BACKGROUND: Allergen immunotherapy (AIT) has been thoroughly documented in randomized controlled trials (RCTs). It is the only immune-modifying and causal treatment available for patients suffering from IgE-mediated diseases such as allergic rhinoconjunctivitis, allergic asthma and insect sting allergy. However, there is a high degree of clinical and methodological heterogeneity among the endpoints in clinical studies on AIT, for both subcutaneous and sublingual immunotherapy (SCIT and SLIT). At present, there are no commonly accepted standards for defining the optimal outcome parameters to be used for both primary and secondary endpoints. METHODS: As elaborated by a Task Force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) Immunotherapy Interest Group, this Position Paper evaluates the currently used outcome parameters in different RCTs and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic rhinoconjunctivitis. RESULTS: Based on a thorough literature review, the TF members have outlined recommendations for nine domains of clinical outcome measures. As the primary outcome, the TF recommends a homogeneous combined symptom and medication score (CSMS) as a simple and standardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner. All outcomes, grouped into nine domains, are reviewed. CONCLUSION: A standardized and globally harmonized method for analysing the clinical efficacy of AIT products in RCTs is required. The EAACI TF highlights the CSMS as the primary endpoint for future RCTs in AIT for allergic rhinoconjunctivitis.

The reaction of Appel salt 1 with 1H-pyrazol-5-amines 2 gives main products N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-1H-pyrazol-5-amines 3, and 6H-pyrazolo[3,4-c]isothiazole-3-carbonitriles 5, together with several minor side products. When the pyrazoles are N-1 methylated, the product ratio 3:5 can be modified by adjusting the pH of the reaction medium: acidic conditions favor formation of the dithiazolylidenes 3, while basic conditions favor formation of pyrazolo[3,4-c]isothiazoles 5. Furthermore, thermolysis of N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-1H-pyrazol-5-amines 3 gives 1H-pyrazolo[3,4-d]thiazole-5-carbonitriles 4. Single crystal X-ray crystallography supports the structure of 4,6-dimethyl-6H-pyrazolo[3,4-c]isothiazole-3-carbonitrile (5a) and helps resolve a previous incorrect structural assignment of 1H-pyrazolo[3,4-d]thiazole-5-carbonitriles 4.

Excess body weight is associated with various types of malignancies. Resistin, originally described as an adipocyte-specific hormone modulating insulin resistance in rodents, may exhibit proliferative, antiapoptotic, proinflammatory, proangiogenic and metastatic properties. Accumulating evidence supports a role of resistin as a risk factor and potential diagnostic and prognostic biomarker in cancer. In this report, the current knowledge about resistin's properties and pathophysiological implications in cancer in the context of dysregulated adipose tissue in obesity is summarized; clinical translations, preventive and therapeutic considerations, and future perspectives in the field of resistin research are discussed. At the same time, several enigmatic issues involving resistin receptor and signaling pathways remain to be clarified in order to unmask its ontological role in cancer pathophysiology.

The issue of violence on the soccer field in our time is a very complicated sport-social phenomenon. The subject has already been extensively researched, but there is still room for further inquiry. In accordance with internationally accepted theoretical tendencies, previous studies examining the issue of violence in soccer in Greece have focused on the understanding of this phenomenon as it relates to either the social conditions in society in general, or to the social characteristics of the spectators of the soccer clubs that are involved in that violence. This study looked at the issue from another point of view. Specifically, it focuses on the understanding of the phenomenon as it relates with the space, the time and the structural conditions under which it is produced. For that purpose, a questionnaire was administered to 696 subjects divided into four different groups of individuals related to soccer. The results, divided in three categories, indicate that, when we examine issues of violence in soccer, we should consider how a variety of socialcultural and emotional conditions inside football stadiums are shaped, keeping in mind that those conditions are specific in each game. This would enable us to differentiate violence in sport from other forms of violence and would assist in understanding the limits of responsibility of football institutions and organizations. Key Words: violence, football stadium, emotional energy, structural characteristics and conditions, expectations.

Bortezomib-dexamethasone is widely used for relapsed myeloma in routine clinical practice, but comparative data versus single-agent bortezomib are lacking. This retrospective analysis compared second-line treatment with bortezomib- dexamethasone and bortezomib using 109 propensity score-matched pairs of patients treated in three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. Propensity scores were estimated using logistic regression analyses incorporating 13 clinical variables related to drug exposure or clinical outcome. Patients received intravenous bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11, in 21-day cycles, alone or with oral dexamethasone 20 mg on the days of/after bortezomib dosing. Median bortezomib cumulative dose (27.02 and 28.60 mg/m2) and treatment duration (19.6 and 17.6 weeks) were similar with bortezomib-dexamethasone and bortezomib, respectively. The overall response rate was higher (75% vs. 41%; odds ratio=3.467; P<0.001), and median time-to-progression (13.6 vs. 7.0 months; hazard ratio [HR]=0.394; P=0.003) and progression-free survival (11.9 vs. 6.4 months; HR=0.595; P=0.051) were longer with bortezomib-dexamethasone versus bortezomib, respectively. Rates of anygrade adverse events, most common grade 3 or higher adverse events, and discontinuations due to adverse events appeared similar between the groups. Two patients per group died of treatment-related adverse events. These data indicate the potential benefit of bortezomib-dexamethasone compared with single-agent bortezomib at first relapse in myeloma. The MMY-2045, APEX, and DOXIL-MMY-3001 clinical trials were registered at, respectively, clinicaltrials.gov identifier: 00908232, 00048230, and 00103506. ©2014 Ferrata Storti Foundation.

Automatic segmentation of the arterial lumen from ultrasound images is an important task in clinical diagnosis. Carotid artery recognition, the first task in lumen segmentation, should be performed in a fully automated, fast, and reliable way to further facilitate the low-level task of arterial delineation. In this paper, a user-independent, real-time algorithm is introduced for carotid artery localization in longitudinal B-mode ultrasound images. The proposed technique acts directly on the raw image, and exploits basic statistics along with anatomical knowledge. The method's evaluation and parameter value optimization were performed on a threefold cross validation basis. In addition, the introduced algorithm was systematically compared with another algorithm for common carotid artery recognition in B-mode scans, separately for multi-frame and single-frame data. The data sets used included 2,149 images from 100 subjects taken from three different institutions and covering a wide range of possible lumen and surrounding tissue representations. Using the optimized values, the carotid artery was recognized in all the processed images in both multi-frame and single-frame data. Thus, the introduced technique will further reinforce automatic segmentation in longitudinal B-mode ultrasound images.

Background: Chemokine receptor signaling pathways are implicated in the pathobiology of renal cell carcinoma (RCC). However, the clinical relevance of CXCR2 receptor, mediating the effects of all angiogenic chemokines, remains unclear. SOCS (suppressor of cytokine signaling)-3 is a negative regulator of cytokine-driven responses, contributing to interferon-α resistance commonly used to treat advanced RCC with limited information regarding its expression in RCC.Methods: In this study, CXCR2 and SOCS-3 were immunohistochemically investigated in 118 RCC cases in relation to interleukin (IL)-6 and (IL)-8, their downstream transducer phosphorylated (p-)STAT-3, and VEGF expression, being further correlated with microvascular characteristics, clinicopathological features and survival. In 30 cases relationships with hypoxia-inducible factors, i.e. HIF-1a, p53 and NF-κΒ (p65/RelA) were also examined. Validation of immunohistochemistry and further investigation of downstream transducers, p-JAK2 and p-c-Jun were evaluated by Western immunoblotting in 5 cases.Results: Both CXCR2 and IL-8 were expressed by the neoplastic cells their levels being interrelated. CXCR2 strongly correlated with the levels of HIF-1a, p53 and p65/RelA in the neoplastic cells. Although SOCS-3 was simultaneously expressed with p-STAT-3, its levels tended to show an inverse relationship with p-JAK-2 and p-c-Jun in Western blots and were positively correlated with HIF-1a, p53 and p65/p65/RelA expression. Neither CXCR2 nor SOCS-3 correlated with the extent of microvascular network. IL-8 and CXCR2 expression was associated with high grade, advanced stage and the presence/number of metastases but only CXCR2 adversely affected survival in univariate analysis. Elevated SOCS-3 expression was associated with progression, the presence/number of metastasis and shortened survival in both univariate and multivariate analysis.Conclusions: Our findings implicate SOCS-3 overexpression in RCC metastasis and biologic aggressiveness advocating its therapeutic targeting. IL-8/CXCR2 signaling also contributes to the metastatic phenotype of RCC cells but appears of lesser prognostic utility. Both CXCR2 and SOCS-3 appear to be related to transcription factors induced under hypoxia. © 2014 Stofas et al.; licensee BioMed Central Ltd.

We investigate the effects of hadronic cascades on the gamma-ray burst (GRB) prompt emission spectra in scenarios of efficient neutrino production. By assuming a fiducial GRB spectrum and a power-law proton distribution extending to ultrahigh energies, we calculate the proton cooling rate and the neutrino emission produced through photopion processes. For this, we employ a numerical code that follows the formation of the hadronic cascade by taking into account non-linear feedback effects, such as the evolution of the target photon field itself due to the contribution of secondary particles. We show that in cases of efficient proton cooling and subsequently efficient high-energy neutrino production, the emission from the hadronic cascade distorts and may even dominate the GRB spectrum. Taking this into account, we constrain the allowable values of the ratio ηp = Lp/Lγ, where Lp and Lγ are the isotropic equivalent proton and prompt gamma-ray luminosities. For the highest value of ηp that does not lead to the dominance of the cascading emission, we then calculate the maximum neutrino luminosity from a single burst and show that it ranges between (0.01-0.6)Lp and (0.5-1.4)Lγ for various parameter sets. We discuss possible implications of other parameters, such as the magnetic field strength and the shape of the initial gamma-ray spectrum, on our results. Finally, we compare the upper limit on ηp derived here with various studies in the field, and we point out the necessity of a self-consistent treatment of the hadronic emission in order to avoid erroneously high neutrino fluxes from GRB models.

Clinical outcomes for patients with multiple myeloma (MM) have improved substantially since the introduction of novel agents including the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide. However, most patients with MM eventually relapse, and prognosis remains poor among patients with relapsed and/or refractory disease. Combination therapy using agents with different mechanisms of action is emerging as an attractive treatment approach in oncology to increase efficacy and/or overcome resistance to standard treatment regimens. This review discusses unmet needs in the treatment of MM and the development of histone deacetylase inhibitors as a treatment modality for MM. © 2013 Informa UK, Ltd.

Photocatalysis has gained relevance in many applications, including production of fuels, green synthesis of added value products and water detoxification. Graphene-TiO2 photocatalysts are attracting great attention, but they should be prepared adequately, protecting the carbon material from the surrounding reactive media, maximizing the contact between TiO2 and graphene, and envisaging solar applications. Hereby, graphene oxide was chemically reduced using vitamin C and glucose (environmental friendly reducing agents) as well as hydrazine, and the evolution of the graphene oxygenated surface groups was systematically analyzed (pHPZC, TPD, TG, XPS, DRUV-Vis, Raman and ATR-FTIR). These functionalities (such as epoxy and hydroxyl groups) mediate the efficient and uniform assembly of the TiO2 nanoparticles on the graphene oxide sheets, leading to highly efficient photocatalysts both under near-UV/Vis and visible light, which is of particular relevance for solar applications. © 2014 Elsevier B.V.