Publications by Year: 2013

The aim of the International Myeloma Working Group was to develop practice recommendations for the management of multiple myeloma (MM) -related bone disease. An interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations based on published data through August 2012. Expert consensus was used to propose additional recommendations in situations where there were insufficient published data. Levels of evidence and grades of recommendations were assigned and approved by panel members. Bisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability.

Excess body weight constitutes a worldwide health problem with epidemic proportions impacting on the risk and prognosis of several disease states including malignancies. It is believed that the metabolic changes associated with weight gain, particularly visceral obesity, and physical inactivity could lead to dysfunctional adipose and muscle tissues causing insulin resistance, low-grade chronic inflammation and abnormal secretion of adipokines and myokines. The complex paracrine and endocrine interconnection between adipokines and myokines reflects a yin-yang balance with important implications in processes such as lipolysis control, insulin sensitivity and prevention from obesity-driven chronic low-grade inflammation and cancer promotion through anti-inflammatory adipokines and myokines. Furthermore, the complex pathophysiology of cancer cachexia is based on the interplay between muscle and adipose tissue mediated by free fatty acids, various adipokines and myokines. The purpose of this editorial is to explore the role of the adipose and muscle tissue interplay in carcinogenesis, cancer progression and cachexia, and to examine the mechanisms underpinning their association with malignancy. Understanding of the mechanisms connecting the interplay of adipokines and myokines with cancer pathophysiology is expected to be of importance in the development of therapeutic strategies against cancer cachexia. Advances in the field of translational investigation may lead to tangible benefits to obese and inactive persons who are at increased risk of cancer as well as to cancer patients with cachexia.

Leptomeningeal carcinomatosis (MC) represents an uncommon, but devasting manifestation of metastatic breast cancer. This is the first systematic review/pooled analysis to synthesize all available data evaluating the efficacy and safety of intrathecal (IT) administration of trastuzumab for the treatment of MC in HER2-positive breast cancer patients. This study was performed in accordance with the PRISMA guidelines. A total of 13 articles (17 patients) were eligible. The mean age of patients at IT trastuzumab administration was 48.2 years (SD 8.4, range 38-66). The mean total dose was 399.8 mg (SD 325.4, range 35-1,110 mg). IT trastuzumab alone or as part of combination therapies seemed to be safe; no serious adverse events were reported in 88.2 % of cases. In 68.8 % of cases, a significant clinical improvement was observed, while stabilization or progression of the disease was noticed in 31.2 % of cases. Cerebrospinal fluid (CSF) response was noted in 66.7 % of cases. The median overall survival was 13.5 months, whereas the median central nervous system progression-free survival (CNS-PFS) was 7.5 months. In 23.5 % of cases, IT trastuzumab was administered beyond CNS progression with a response noticed in 75 % of cases and a CNS-PFS of 9.4 months. The cumulative dose of IT trastuzumab given was 1,040 mg (SD 697.9, median 1,215, range 55-1,675). The protective effect of prior radio- or neurosurgery upon CNS-PFS was sizeable but did not reach formal statistical significance (HR 0.28, 95 % CI 0.06-1.37). Clinical improvement (HR 0.14, 95 % CI 0.02-0.91) and CSF response (HR 0.09, 95 % CI 0.01-0.89) were associated with longer CNS-PFS. IT trastuzumab administration seems to represent a safe and in some cases effective option for the treatment of HER2-positive breast cancer patients with leptomeningeal involvement. However, clinical trials are urgently needed to establish the definite role of IT trastuzumab in HER2-positive metastatic breast cancer patients with MC. © 2013 Springer Science+Business Media New York.

The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project.

The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project.

The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project.

The scope of the research project is to investigate the consequences of climate change on deltaic plains, as one of the most vulnerable coastal and wealth-producing ecosystems. The Pinios river delta, located in the region of Thessaly (Greece) has been selected as a case study, as one of the largest Greek rivers with very limited flow controls. But, despite the fact that deltaic plain is part of the NATURA network, human intervention continuous to occur at an increasing rate. The main objectives of the project are to: (i) study the relative contribution of fluvial fluxes (water/sediment), nearshore hydrodyanmics and climate conditions in the formation and evolution of deltas; (ii) evaluate the impact of human activities in the evolution of the River Pinios delta (e.g., alteration of riverine fluxes, agricultural pollution, over-pumping of the aquifer); (iii) assess and to evaluate quantitatively changes in the deltaic environment for different climate change scenarios, i.e. water balance, issues of water quality, desertification, coastal erosion, inundation; (iv) investigate the interaction between natural processes and parameters associated with socio-economic development and use; (v) develop Sustainable Development Strategies for the natural deltaic system, in order to mitigate the consequences of the climate change, towards a better management of the wealth- producing resources (i.e. fresh water yield); (vi) contribute to the training of young scientists in environmental issues, related to the impact of the climate change on coastal environments; and (vii) disseminate science based management strategies to the local and scientific communities. During the first phase of project implementation, the study of the surface and ground water and their interrelationship is investigated through: (i) the climatological conditions of the deltaic plain and the drainage basin; (ii) the determination of the subsurface geological/stratigraphical information provided by geophysical data; (iii) surface and water fluxes estimated on monthly measurements (quantitative and qualitative) of river flow and phreatic water table.

The scope of the research project is to investigate the consequences of climate change on deltaic plains, as one of the most vulnerable coastal and wealth-producing ecosystems. The Pinios river delta, located in the region of Thessaly (Greece) has been selected as a case study, as one of the largest Greek rivers with very limited flow controls. But, despite the fact that deltaic plain is part of the NATURA network, human intervention continuous to occur at an increasing rate. The main objectives of the project are to: (i) study the relative contribution of fluvial fluxes (water/sediment), nearshore hydrodyanmics and climate conditions in the formation and evolution of deltas; (ii) evaluate the impact of human activities in the evolution of the River Pinios delta (e.g., alteration of riverine fluxes, agricultural pollution, over-pumping of the aquifer); (iii) assess and to evaluate quantitatively changes in the deltaic environment for different climate change scenarios, i.e. water balance, issues of water quality, desertification, coastal erosion, inundation; (iv) investigate the interaction between natural processes and parameters associated with socio-economic development and use; (v) develop Sustainable Development Strategies for the natural deltaic system, in order to mitigate the consequences of the climate change, towards a better management of the wealthproducing resources (i.e. fresh water yield); (vi) contribute to the training of young scientists in environmental issues, related to the impact of the climate change on coastal environments; and (vii) disseminate science based management strategies to the local and scientific communities. During the first phase of project implementation, the study of the surface and ground water and their interrelationship is investigated through: (i) the climatological conditions of the deltaic plain and the drainage basin; (ii) the determination of the subsurface geological/stratigraphical information provided by geophysical data; (iii) surface and water fluxes estimated on monthly measurements (quantitative and qualitative) of river flow and phreatic water table.

The volatile constituents of 22 samples of commercial beers (lager, ale, and lambic) were isolated using adsorption resin XAD-4 and analyzed by gas chromatography, using mass-spectrometric detection. The presence of 63 volatile components was examined in each sample. Major common compounds identified in all of the studied samples were 2-methylpropanol (0.77-12.9%), 3-methylbutanol (32.0-55.5%), phenylethanol (18.7- 58.8%), and tyrosol (0.69-5.82%), expressed as TIC percent. Most other components were found in various concentrations but their presence was not uniformly distributed in all the studied beers. One of the minor volatile compounds, 2-(3H)-benzoxazolone, was found only in beers made with wheat malt. Additionally, for the first time, tryptophol acetate was identified as beer constituent. Finally, principal component analysis of the volatile compounds was able to discriminate the group of beers containing wheat. © 2013 American Society of Brewing Chemists, Inc.

Innovative redox electrolytes for dye-sensitized solar cells (DSCs) were prepared using binary mixtures of 1-methyl-3-propylimidazolium iodide (MPII) with 1-alkyl-methylimidazolium tricyanomethanide, CνmimTCM (ν = 2, 4, 6, 8) ionic liquids (ILs) to lower the high viscosity of MPII. The investigation of the physicochemical properties of the IL blends as a function of temperature has shown that both density and viscosity strongly depend on the kind of the Cνmim cation in the mixture. The corresponding Raman spectra were dominated by the vibrational modes of the IL components in an additive way and confirmed the absence of any specific interaction, independent of the Cν alkyl chain length. The electrochemical properties (triiodide diffusion coefficients, specific conductivity), determined in symmetrical thin layer cells using polarization and electrochemical impedance spectroscopy (EIS) measurements, have shown that both diffusion and conductivity decreased with increasing viscosity, and further confirmed the electrolytes' compatibility with the cathode. Incorporation of the novel electrolytes in DSC devices revealed a systematic dependence of the cell photovoltaic performance on the alkyl chain length of CνmimTCM; the maximum power conversion efficiency exceeded 5 and 6.5% under 1 and 0.1 sun AM 1.5 G illumination, respectively, for the ionic liquid with the shortest alkyl chain. The solar cells were further characterized by EIS (IMPS) spectroscopy, exploring charge recombination dynamics and identifying conduction band edge shifts. Solidification of the electrolytes with silica nanoparticles, demonstrated that the ionic liquid electrolytes with long chain length (ν > 4) not only retain their efficiencies, but also exhibit a 22% efficiency enhancement, which is most pronounced for the electrolytes employing ionic liquids with the longest (hexyl- and octyl-) alkyl chains. © 2013 The Royal Society of Chemistry.

Central nervous system (CNS) involvement in patients with primary mediastinal large B-cell (PMLBCL) lymphoma is a rare event, occurring in approximately 6% of patients, on the basis of the review of the literature prior to induction of Rituximab. The aim of this retrospective study was to describe the incidence of CNS relapse among 100 consecutive patients with PMLBCL who were treated with R-CHOP±RT in comparison to patients treated with CHOP±RT (n=45) in 11 hospitals in Greece. Two patients experienced a CNS relapse, representing an overall frequency of 2.0% in R-CHOP treated patients and a 2-year actuarial incidence of 2.3%. Both patients had isolated CNS relapses. The incidence of CNS relapse after CHOP without Rituximab was 2/45 (4.4%) for a 2-year actuarial incidence of 7.5% (p=0.29). Again, both patients had isolated CNS relapses. Parenchymal-only localizations accounted for 3/4 cases. Risk factors for CNS involvement could include leukocytosis, poor performance status and higher age-adjusted International Prognostic Index, although their impact was weakened by competing risk survival analysis. Both patients relapsing after R-CHOP required CNS radiotherapy to achieve a complete remission and be forwarded to high-dose therapy and autologous stem cell transplantation: They are both alive and disease-free 18 and 23months after CNS relapse. Both cases relapsing after CHOP without Rituximab were salvaged by CNS radiotherapy (one also received intrathecal chemotherapy) entering long-term remissions. In conclusion, CNS relapses are rare in PMLBCL tending to be isolated in the CNS, probably reflecting the persistence of latent CNS disease than dissemination of resistant disease. The impact of Rituximab in reducing CNS relapses remains unknown. Established risk factors for CNS involvement in aggressive lymphomas may not be helpful in assessing the risk of CNS recurrence in this disease. Routine CNS prophylaxis is not probably required in PMLBCL. © 2012 John Wiley & Sons, Ltd.

This review starts with an introduction on the theoretical aspects of biopharmaceutics and developments in this field from mid-1950s to late 1970s. It critically addresses issues related to fundamental processes in oral drug absorption such as the complex interplay between drugs and the gastrointestinal system. Special emphasis is placed on drug dissolution and permeability phenomena as well as on the mathematical modeling of oral drug absorption. The review ends with regulatory aspects of oral drug absorption focusing on bioequivalence studies and the US Food and Drug Administration and European Medicines Agency guidelines dealing with Biopharmaceutics Classification System and Biopharmaceutic Drug Disposition Classification System. (C) 2013Wiley Periodicals, Inc. and the American Pharmacists Association

Conventional experimental models of respiratory allergy have contributed greatly to our current knowledge of the pathophysiology of allergic airway diseases; nevertheless, they are contingent upon unnatural sensitization techniques, entailing adjuvant-aided intraperitoneal (i.p) administration of antigen. Currently, there is a growing appreciation of the impact of tolerance mechanics in the pathophysiology of respiratory allergy. Thus, inasmuch as adjuvants exert a robust tolerance-modifying action, a transition from the conventional method of experimental sensitization to one that is more naturally and clinically relevant becomes important. We therefore opted to survey the literature and identify agents that could interfere with sensitization mechanics following non-adjuvant-aided airway exposure of laboratory rodents to aeroallergen. GM-CSF was found to exert robust Th2-polarizing action in this setting. Conversely, IL-10 fulfilled an important, albeit not so clear-cut, tolerance-favoring role; TGF-β was also identified as a likely instigator of tolerogenesis. The role of Notch signaling in the sensitization versus tolerance dilemma appeared to be important but diverse. Collectively, these factors appeared to profoundly and diversely modulate the balance between tolerance and sensitization in naturally relevant experimental models of allergic airway disease.

Kiwifruit is a common cause of food allergy. Symptoms range from mild to anaphylactic reactions.|We sought to elucidate geographic differences across Europe regarding clinical patterns and sensitization to kiwifruit allergens. Factors associated with the severity of kiwifruit allergy were identified, and the diagnostic performance of specific kiwifruit allergens was investigated.|This study was part of EuroPrevall, a multicenter European study investigating several aspects of food allergy. Three hundred eleven patients with kiwifruit allergy from 12 countries representing 4 climatic regions were included. Specific IgE to 6 allergens (Act d 1, Act d 2, Act d 5, Act d 8, Act d 9, and Act d 10) and kiwifruit extract were tested by using ImmunoCAP.|Patients from Iceland were mainly sensitized to Act d 1 (32%), those from western/central and eastern Europe were mainly sensitized to Act d 8 (pathogenesis-related class 10 protein, 58% and 44%, respectively), and those from southern Europe were mainly sensitized to Act d 9 (profilin, 31%) and Act d 10 (nonspecific lipid transfer protein, 22%). Sensitization to Act d 1 and living in Iceland were independently and significantly associated with severe kiwifruit allergy (odds ratio, 3.98 [P = .003] and 5.60 [P < .001], respectively). Using a panel of 6 kiwifruit allergens in ImmunoCAP increased the diagnostic sensitivity to 65% compared with 20% for skin prick tests and 46% ImmunoCAP using kiwi extract.|Kiwifruit allergen sensitization patterns differ across Europe. The use of specific kiwifruit allergens improved the diagnostic performance compared with kiwifruit extract. Sensitization to Act d 1 and living in Iceland are strong risk factors for severe kiwifruit allergy.

Proposition initiale: Avant toute tentative de définition métathéorique lakatienne de l’analyse géopolitique systémique et de définition ontologique de ses notions structurelles, nous admettrons que l’approche théorique de l’analyse géopolitique systémique contemporaine, laquelle est de nature interdisciplinaire et se fonde sur la géographie politico-économique1 participe sur un pied d’égalité à l’ensemble des approches théoriques qui constituent le programme de recherche géopolitique néo-positiviste.

A submarine survey along the coasts of Ithaca and Fiscardo has permitted the identification of fossil shorelines produced by recent co-seismic movements. In both areas a tidal notch slightly submerged below present MSL was observed at various sites. This “modern” notch is known to have been submerged by the global sea-level rise during the 19th and 20th centuries. The depth after tide and air-pressure correction of the vertex of the “modern” notch (= MSL before the recent sea-level rise) was measured between -19±6 and -25±6 cm at Fiscardo and between -34±6 and -43±6 cm at Ithaca. The presence of this “modern” notch at the same depth on both sides of the Ionian Thrust would give evidence that both areas were not affected by the co-seismic vertical movements that occurred in 1953 in the wider area, while a greater depth in Ithaca could be an effect of co-seismic subsidence. Both cases are discussed and analysed in this paper. Assuming that the development of the “modern” notch was produced by bioerosion, it is possible to deduce a period of relative sea-level stability before the 19th century during 2.4 to 4 centuries at Ithaca and 1.5 to 4 centuries at Fiscardo. Over the longer term, the tectonic behavior of Ithaca differs from Fiscardo. At Ithaca no evidence of emergence has been found and Holocene vertical movements have been only of subsidence: fossil submerged tidal notches can be distinguished below MSL at depths (±6 cm) of about -40 (modern), -60, -75, -90, -100, -120, -130, -140, -150 and -220 cm. A southward tilting of the island is suggested from the -110 cm notch, but this is not the case for the -70 cm shoreline. On the east coast of Fiscardo Peninsula impacts of ancient earthquakes have left some marks (±6 cm) of emergence at about +15 and +40 cm, and of submergence at about -20 (modern) -35, -50, -60, -70, -80, -90, -100 and -230 cm, with even some evidence of past uplift and subsidence at the same sites.

Analytical radially self-similar models are the best available solutions describing disk-winds, but they need several improvements. We introduce models of jets from truncated disks, i.e. numerical simulations based on a radially self-similar MHD solution but including the effects of a finite radius of the jet-emitting disk, hence the outflow. We compare these models with available observational data, by varying the jet density and velocity, the mass of the protostar, the radius of this truncation and the inclination. In order to our models with observed jet widths inferred from recent optical images taken with HST and ground-based AO observations, we create emission maps in different forbidden lines, and from such emission maps, determine the jet width as the full-width half-maximum of the emission. We can reproduce the jet widths of several examples and its variations very well. We conclude that truncation - i.e. taking the finite radius of the jet launching region into account - is needed to reproduce the observed jet widths, and our simulations limit the possible range of truncation radii. The effects of inclination are important for modeling the intrinsic variations seen in observed jet widths. Our models can be used to infer the inclinations in the observed sample independently.

The anatomy of the dorsiventral, amphistomatic leaf of Papaver rhoeas was investigated. It was a simple structure possessing large epidermal cells having their vacuole impregnated with glycoproteins which varied in texture, forming a dense, hard core in the middle of the vacuole. Slender rays of cisternae radiated from the dense central core to the cell wall. Thin-walled palisade cells presented a unique, lobed shape probably creating larger surfaces for gas exchange. Mesophyll cells secreted phenolics, condensed tannins, alkaloids, terpene containing steroids and sesquiterpenes. P. rhoeas although being a therophyte, has adopted some structural features common in mediterranean phanerophytes. © 2013 Taylor & Francis Group, LLC.

The dorsiventral, amphistomatic, hairy leaf of Pelargonium odoratissimum was lacking the variety of the anatomical features considered advantages for the Mediterranean plant life compared to the leaf of most Mediterranean xerophytes. Conversely, it had a well-equipped and intensely functioning secretory apparatus. Light, scanning, and transmission electron microscopy were employed to investigate the leaf structure while histochemical reactions traced the nature of the secreted metabolites. The numerous trichomes of the leaf were very active in producing phenolics, terpenes, and flavonoids mixed in a fragrant essential oil accumulated in an ovoid chamber at the top of each secreting hair. In-vitro cell cultures may be used for the production of novel compounds from low-cost precursors. © 2013 Taylor & Francis Group, LLC.

The MM-015 trial assessed the effect of lenalidomide-based therapy on health-related quality of life. Patients (n=459) with newly diagnosed multiple myeloma aged 65 years or over were randomized 1:1:1 to nine 4-week cycles of lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance; or lenalidomide, melphalan, and prednisone, or melphalan and prednisone, with no maintenance therapy. Patients completed health-related quality of life questionnaires at baseline, after every third treatment cycle, and at treatment end. Health-related quality of life improved in all treatment groups during induction therapy. Patients receiving lenalidomide maintenance had the most pronounced improvements, Global Health Status/Quality of Life (P<0.05), Physical Functioning (P<0.01), and Side Effects of Treatment (P<0.05) out of 6 pre-selected health-related quality of life domains. More patients receiving lenalidomide maintenance achieved minimal important differences (P<0.05 for Physical Functioning). Therefore, lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance, improves health-related quality of life in patients with newly diagnosed multiple myeloma. (Clinicaltrials.gov identifier NCT00405756). © 2013 Ferrata Storti Foundation.

Since its discovery as an adipocyte-secreted hormone, leptin has been found to impact food intake, energy homeostasis, and metabolism through its effects on the central nervous system and peripheral organs. Recent research indicates that leptin may also be involved in cognition, immune function, and bone metabolism. These findings place leptin at the intersection of neuroendocrinology and metabolism, and possibly immune function, and render it an appealing therapeutic target for several niche areas of unmet clinical need. Current evidence regarding classic and emerging roles of leptin as well as the pros and cons of its potential clinical use are summarized herein.

Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes.

Cet article, basé sur les sources des textes sacrés du Coran ainsi que sur des textes de kanunistes importants de l’Islam, soutient le point de vue que le seul qui a le pouvoir absolu de déclarer le Djihad (en arabe égyptien: Gehad) c’est le Calife de l’Oumma qui a été choisi selon la Loi Sacrée (Shari’a). Cependant, puisque dans les circonstances actuelles l’Oumma des croyants (des musulmans) n’a pas la structure califale et donc n’a pas du calife, personne ne peut déclarer le Gehad selon les dispositions de la Loi Sacrée (Shari’a). Ainsi, «la Réouverture des Portes de l’Idjtihad (en arabe égyptien: Edgehad)» que les islamistes tentent et leur indifférence pour l’idjma’a (en arabe égyptien: egma’a) des kanunistes ne permet pas le support, du point de vue juridique, de la «déclaration du Gehad» par les dirigeants des divers secteurs des mouvements islamistes.

Le présent article, qui a été publié en français, en anglais et en turc dans le cadre de l’exposition sur Smyrne est accompagné d’une riche illustration des œuvres d’art du XVIIIe  siècle. En nous appuyant sur des récits viatiques nous avons étudié l’image de l’Orient qu’ils décrivaient. Après avoir brièvement abordé l’héritage iconographique de l’Orient nous traitons de la thématique adoptée dans leurs œuvres d’art.  Plus précisément, nous examinons, la présence du paysage et l’évolution de sa représentation ainsi que  l’importance de l’intégration des habitants dans les compositions des voyageurs français. Ensuite, nous analysons les caractéristiques du « voyage archéologique » s’attardant sur ceux du comte de Caylus, des Fourmont et de Julien-David Leroy. Finalement nous étudions le « voyage pittoresque » dont le caractère polymorphe a rendu les différents aspects de l’Orient.

This review summarizes the findings and importance of 12 articles from research at Columbia University in New York City that were among the most cited in the literature between 2006 and 2011. The 12 articles summarized in this review made important contributions to the field of Alzheimer's disease in the last 5 years. Four of the articles established the Mediterranean diet as a food consumption pattern that may prevent Alzheimer's disease in addition to physical activity. Two of the articles advanced our knowledge of predictors of conversion from mild cognitive impairment to dementia. Four of the articles provided important knowledge of risk factors for the progression of Alzheimer's disease and its complications. Lastly, one of the articles laid the theoretical framework for the study of cognitive reserve, an important modifier of the manifestation of Alzheimer's disease. These studies have advanced our knowledge about risk factors, modifiers, and progression of late onset Alzheimer's disease

This book combines legal as well as political and theoretical questions in a variety of contexts, ranging from legal issues in the early modern period to critical explorations of law/s, justice and textuality in contemporary literature and culture. The essays in this volume offer critical perspectives on the role of literature and theory in relation to the law and explore otherness and justice in early modern, Victorian and contemporary texts, postmodern theory, colonial and postcolonial contexts and popular culture. Examining how legal and literary narratives construct, repress, legitimise, but also enable the Other, this volume offers new insights into forms of alterity, marginality and exclusion and articulates the imperative need to reconfigure issues of justice as always intertwined with the Other.

BACKGROUND: International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe. RESULTS: Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 2002-2007 were included.We identified 457 clusters including 1330 persons (31.2% of all patients). The cluster size ranged between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that consisted only of patients originating from the same country. In addition, 135 patients (10.2%) were in a cluster including only individuals from neighboring countries. Finally, 208 patients (15.6%) clustered with individuals from countries without a common border. Clustering with patients from the same country was less prevalent in patients being infected with B subtype (P-value <0.0001), in men who have sex with men (P-value <0.0001), and in recently infected patients (P-value =0.045). CONCLUSIONS: Our findings indicate that the transmission of HIV-1 in Europe is predominantly occurring between patients from the same country. This could have implications for HIV-1 transmission prevention programmes. Because infections through travelling between countries is not frequently observed it is important to have good surveillance of the national HIV-1 epidemics.

The major risk factor of perinatal transmission of Hepatitis B virus (HBV) infection is the level of maternal HBV-deoxyribonucleic acid (DNA) during the third trimester of pregnancy. The primary aim of this study was to evaluate the hematological and biochemical status in Hepatitis B e-antigen (HBeAg)-negative chronic HBV-infected pregnant women and to correlate the findings with the presence or absence of viremia. Ninety-five consecutive chronic HBV-infected pregnant women were evaluated between the 28th and 32nd week of gestation. Viral load was determined by using the COBAS TaqMan HBV test. Sixty-nine women were evaluated and 14 of them exhibited HBV-DNA levels higher than 2000 IU·ml. In this study, viremic women exhibited significantly higher alanine aminotransferase (ALT), creatinine, and uric acid values as well as significantly lower white blood cell count compared with nonviremic women. There was also a significant statistical difference concerning ALT/sodium ratio between viremic and nonviremic women (0.20 ± 0.22 vs. 0.10 ± 0.09, respectively, p= .024). The optimal cutoff points discriminating those women with a high probability to have detectable serum HBV-DNA were 0.092 for ALT/sodium ratio (sensitivity = 73.0%, specificity = 61.5%, area under the receiver operating characteristic curve [AUC] = 71.05%) and 12.8 IU/L for ALT (sensitivity = 73.0%, specificity = 63.0%, AUC = 72.2%). Chronic HBV-infected pregnant women with ALT/sodium ratio ≥ 0.11 had the higher probability of having serum HBV-DNA levels higher than 2000 IU/ml (sensitivity = 76.92%, specificity = 58%, AUC = 62.38%). Presence of HBV-DNA in maternal blood during the third trimester of pregnancy is significantly associated with maternal serum ALT levels in HBeAg-negative chronic HBV-infected pregnant women. Women with an ALT/sodium ratio greater than 0.092 have the higher probability of HBV-DNA presence in maternal blood whereas an ALT/sodium ratio greater than 0.11 could discriminate those women with HBV-DNA levels higher than 2000 IU/ml.

The influence of microscale and mesoscale meteorology on the local scale variation of air temperature cannot be correctly simulated by the coarse resolution Global Climate Models. The scope of this work is to develop a hybrid dynamic-statistical downscaling procedure and quantify its predictive ability to estimate air temperature variability at finer spatial scales. The study focuses on the warm period of the year (June - August) and the method is applied to eight sites located in Greece with different topographical characteristics. The two-step methodology initially involves the dynamic downscaling of coarse resolution climate data via the RegCM4 regional climate model and subsequently the statistical downscaling of the modeled outputs by training site-specific artificial neural networks (ANN). The RegCM4 model is employed to enhance the representativity of the dataset, while the ANNs are used as function approximators to model the relationship between a number of atmospheric predictor variables and the observed air temperature time series. An insight of the ANN transfer function is obtained by examining the relative contribution of each input variable. The performance of the methodology is evaluated and the results indicate significant improvement from the inclusion of the ANN models in downscaling air temperature. © 2013 Global NEST Printed in Greece. All rights reserved.

OBJECTIVES: To examine in an observational study (1) relationships between cholinesterase inhibitors (ChEI) and memantine use, and functional and cognitive end points and mortality in patients with Alzheimer's disease (AD); (2) relationships between other patient characteristics and these clinical end points; and (3) whether effects of the predictors change across time. METHODS: The authors conducted a multicenter, natural history study that included three university-based AD centers in the United States. A total of 201 patients diagnosed with probable AD with modified Mini-Mental State Examination (MMSE) scores ≥ 30 at study entry were monitored annually for 6 years. Discrete-time hazard analyses were used to examine relationships between ChEI and memantine use during the previous 6 months reported at each assessment, and time to cognitive (MMSE score ≤ 10) and functional (Blessed Dementia Rating Scale score ≥ 10) end points and mortality. Analyses controlled for clinical characteristics, including baseline cognition, function, and comorbid conditions, and presence of extrapyramidal signs and psychiatric symptoms at each assessment interval. Demographic characteristics included baseline age, sex, education, and living arrangement at each assessment interval. RESULTS: ChEI use was associated with delayed time in reaching the functional end point and death. Memantine use was associated with delayed time to death. Different patient characteristics were associated with different clinical end points. CONCLUSIONS: Results suggest long-term beneficial effects of ChEI and memantine use on patient outcomes. As for all observational cohort studies, observed relationships should not be interpreted as causal effects.

Laboratory-size dye solar cells (DSCs), based on industrially feasible materials and processes employing liquid electrolytes, have been developed. Cells based on two electrolyte solvents with different physical properties were subjected to thermal stress test at 80 C for 2000 h in the dark to monitor their long-term thermal stability. The DSCs incorporating a methoxypropionitrile (MPN)-based electrolyte presented a severe efficiency loss at 1 sun AM 1.5G of more than 70% upon thermal aging, while the solar cells using tetraglyme (TG) as a high boiling point solvent attained a promising stability with only 20% loss of performance. To better understand the above behavior, systematic experiments, including optical microscopy, linear sweep voltammetry, UV-vis absorption, electrochemical impedance, and Raman spectroscopies were conducted. Virtually no dye degradation/desorption, electrolyte decomposition, semiconductor passivation, or loss of cathode activity could be identified. For the MPN-based cells, a sharp decrease in the short-circuit photocurrent was observed at high illumination intensities following thermal stress, attributed to charge-transfer limitations due to severe triiodide loss, verified by different experimental techniques. These degradation effects were efficiently mitigated by replacing MPN with the high-boiling-point solvent in the electrolyte. © 2013 American Chemical Society.

The Small Magellanic Cloud (SMC) is host to approximately 100 High-Mass X-ray Binaries (HMXBs), predominantly Be X-ray Binaries (BeXRBs), a number which is surprisingly high when compared to the Milky Way. As these galaxies present different metallicities it is reasonable to ask if their populations of HMXBs are different. In order to address this we investigated their properties such as their spectral types and orbital parameters (periods and eccentricities). We find no apparent differences, implying that the nature of these systems is similar which sets at the same time strong constraints on the magnitude of supernova kicks in low metallicities. In order to extend the sample of BeXRBs we performed a systematic photometric survey of selected active regions of the SMC. Since the optical counterparts of the BeXRBs display Halpha excess they can be identified through Halpha imaging. Observations in 5 regions with the Wide Field Imager at the 2.2m MPG/ESO telescope yield approximately 24000 Halpha emitting stars. By cross-correlating these sources with those identified in the Chandra and XMM-Newton shallow surveys of the SMC and the census of HMXBs of Liu et al. (2005), we find 34 Halpha emitting X-ray sources. These are most likely BeXRBs, which we will confirm with follow-up spectroscopic runs.

BACKGROUND: Prostate cancer (PCa) is characterised by great heterogeneity of the disease progression rate. Tumours range from insignificant and not life threatening to high risk for relapse ones. Consequently, a large number of patients undergo unnecessary treatment. miR-145 is a well-documented tumour suppressor and its expression, which is regulated by the p53 pathway, has been found to be decreased in the majority of human malignancies. The aim of our study was to evaluate the clinical utility of miR-145 for the prognostication of PCa. METHODS: Total RNA was isolated from 137 prostate tissue specimens obtained from 73 radical prostatectomy-treated PCa patients and 64 transurethral- or open prostatectomy-treated benign prostate hyperplasia (BPH) patients. Following polyadenylation and reverse transcription, miR-145 levels were determined by quantitative real-time PCR assay, using SNORD48 (RNU48) for normalisation purposes. RESULTS: Downregulated miR-145 expression was found in PCa compared with BPH patients. The reduction of miR-145 expression in PCa was correlated with higher Gleason score, advanced clinical stage, larger tumour diameter and higher prostate-specific antigen (PSA) and follow-up PSA levels. In addition, higher risk for biochemical recurrence and significantly shorter disease-free survival (DFS) was found for the PCa patients expressing lower miR-145. Focusing on 'low- and intermediate-recurrence risk' PCa patients, miR-145 loss was revealed to be a reliable predictor of biochemical relapse and poor DFS independent from Gleason score, clinical stage, PSA and patients' age. CONCLUSION: The loss of the tumour-suppressor miR-145 increases the risk for disease progression and predicts the poor survival of PCa patients.

Introduction and hypothesis: Congenital vaginal aplasia is a condition with devastating implications for fertility and sexuality. However, little is known on whether urinary symptomatology is more common prior and following vaginal lengthening procedures in these women. Methods: We performed a prospective observational study of 19 women with vaginal agenesis before and after vaginal dilation treatment or a laparoscopic Vecchietti procedure. All women completed the ICIQ FLUTS questionnaire before and after treatment in order to assess incidence and changes in urinary symptomatology. Results: Urinary symptoms were present in 53{%} of women prior to treatment. The majority of bladder symptoms were not significantly altered by treatment, except for incomplete bladder emptying. Women following the Vecchietti procedure had increased urinary hesitancy and a poorer steam compared with those completing dilation treatment. The longer the vaginal length, the greater the urinary frequency. Conclusion: Women with vaginal agenesis had significant levels of urinary symptoms and to our knowledge this has not been reported before. The majority of symptoms were not altered by treatment. © 2012 The International Urogynecological Association.

Malassezia yeasts are commensal microorganisms, which under insufficiently understood conditions can become pathogenic. We have previously shown that specific strains isolated from diseased human skin can preferentially produce agonists of the aryl hydrocarbon receptor (AhR), whose activation has been linked to certain skin diseases. Investigation of skin scale extracts from patients with Malassezia-associated diseases demonstrated 10-to 1,000-fold higher AhR-activating capacity than control skin extracts. Liquid chromatography-tandem mass spectrometry analysis of the patients’ extracts revealed the presence of indirubin, 6-formylindolo[3,2-b]carbazole (FICZ), indolo[3,2-b]carbazole (ICZ), malassezin, and pityriacitrin. The same compounds were also identified in 9 out of 12 Malassezia species culture extracts tested, connecting their presence in skin scales with this yeast. Studying the activity of the Malassezia culture extracts and pure metabolites in HaCaT cells by reverse transcriptase real-time PCR revealed significant alterations in mRNA levels of the endogenous AhR-responsive genes Cyp1A1, Cyp1B1, and AhRR. Indirubin-and FICZ-activated AhR in HaCaT and human HepG2 cells with significantly higher, yet transient, potency as compared with the prototypical AhR ligand, dioxin. In loco synthesis of these highly potent AhR inducers by Malassezia yeasts could have a significant impact on skin homeostatic mechanisms and disease development. © 2013 The Society for Investigative Dermatology.

Kriging interpolation technique is adapted to create the mapping of surface ozone seasonality and trends across Europe during 1997-2006, based on European Monitoring and Evaluation Programme ground measurements. The climatology, the annual and seasonal trends and the altitude above sea level (asl) dependence were studied as well as the relation with the North Atlantic Oscillation (NAO). The mean seasonal cycle amplitude and seasonal maximum display an increasing gradient from northwest to southeast, with high levels in Austria and eastern Mediterranean. Significantly close to 0 positive trends appear in UK, Slovakia, southern Scandinavia and Austria in winter and autumn. In Northern Hemisphere winter (December-February), about 40 % of near-surface ozone variability in the western edge of Europe may be attributed to circulation changes and ozone precursors' transport related to NAO. © 2013 Springer Science+Business Media Dordrecht.

INTRODUCTION: Our objective was to investigate potential associations between maxillary sinus floor extension and inclination of maxillary second premolars and second molars in patients with Class II Division 1 malocclusion whose orthodontic treatment included maxillary first molar extractions. METHODS: The records of 37 patients (18 boys, 19 girls; mean age, 13.2 years; SD, 1.62 years) treated between 1998 and 2004 by 1 orthodontist with full Begg appliances were used in this study. Inclusion criteria were white patients with Class II Division 1 malocclusion, sagittal overjet of ≥4 mm, treatment plan including extraction of the maxillary first permanent molars, no missing teeth, and no agenesis. Maxillary posterior tooth inclination and lower maxillary sinus area in relation to the palatal plane were measured on lateral cephalograms at 3 time points: at the start and end of treatment, and on average 2.5 years posttreatment. Data were analyzed for the second premolar and second molar inclinations by using mixed linear models. RESULTS: The analysis showed that the second molar inclination angle decreased by 7° after orthodontic treatment, compared with pretreatment values, and by 11.5° at the latest follow-up, compared with pretreatment. There was evidence that maxillary sinus volume was negatively correlated with second molar inclination angle; the greater the volume, the smaller the inclination angle. For premolars, inclination increased by 15.4° after orthodontic treatment compared with pretreatment, and by 8.1° at the latest follow-up compared with baseline. The volume of the maxillary sinus was not associated with premolar inclination. CONCLUSIONS: We found evidence of an association between maxillary second molar inclination and surface area of the lower sinus in patients treated with maxillary first molar extractions. Clinicians who undertake such an extraction scheme in Class II patients should be aware of this potential association and consider appropriate biomechanics to control root uprighting.

A hindcast simulation in the Aegean–Levantine basins for the years 1960–2000 is performed, using an eddy resolving ocean model (1°/30). The model incorporates a 6-h atmospheric forcing provided by the ARPERA and captures the observed variability of the 40-years. The Eastern Mediterranean Transient (EMT) is the most prominent climatic event of the period. We investigate the impact of the atmospheric versus lateral forcing on the buoyancy content of the Aegean–Levantine basins. During the pre-EMT period, the basins’ buoyancy content is lowered by surface fluxes by about 1.5×10−8m2s−3 in the Aegean Sea, mostly related to surface heat loss, and lateral fluxes by about 0.9×10−8m2s−3, mostly related to salt flux, with the Levantine changes leading those of the Aegean. Furthermore, while long-term trends of surface and lateral inputs are preconditioning the changes in the Aegean stratification, it is the extreme heat loss pulses, related to the variability of the wind field that is controlling the formation processes by abruptly lowering the buoyancy content. Those events are possibly linked to an eastern Mediterranean bimodal atmospheric oscillation, with the anomalous surface heat fluxes shifting from the Levantine in the 1960s to the Aegean in the 1990s. The central Aegean due to its topography and thermohaline properties trigger events of excessive formation and producing the Aegean’s densest waters. During the EMT winters the central Aegean lower layers contain very dense waters, with σΘ larger than 29.3kgm−3. These waters form the core of the water mass outflowing in the Eastern Mediterranean, after being mixed with ambient waters along their southward flow. The outflowing layer is characterized by density of 29.21kgm−3. The deepest parts of the NW Levantine is initially filled with the new water mass, which later spreads to the SE parts of the basin, flowing over the Eastern Mediterranean Ridge.

OBJECTIVE: This meta-analysis aims to quantitatively synthesize all studies that examine the association between adherence to a Mediterranean diet and risk of stroke, depression, cognitive impairment, and Parkinson disease. METHODS: Potentially eligible publications were those providing effect estimates of relative risk (RR) for the association between Mediterranean diet and the aforementioned outcomes. Studies were sought in PubMed up to October 31, 2012. Maximally adjusted effect estimates were extracted; separate analyses were performed for high and moderate adherence. RESULTS: Twenty-two eligible studies were included (11 covered stroke, 9 covered depression, and 8 covered cognitive impairment; only 1 pertained to Parkinson's disease). High adherence to Mediterranean diet was consistently associated with reduced risk for stroke (RR = 0.71, 95% confidence interval [CI] = 0.57-0.89), depression (RR = 0.68, 95% CI = 0.54-0.86), and cognitive impairment (RR = 0.60, 95% CI = 0.43-0.83). Moderate adherence was similarly associated with reduced risk for depression and cognitive impairment, whereas the protective trend concerning stroke was only marginal. Subgroup analyses highlighted the protective actions of high adherence in terms of reduced risk for ischemic stroke, mild cognitive impairment, dementia, and particularly Alzheimer disease. Meta-regression analysis indicated that the protective effects of Mediterranean diet in stroke prevention seemed more sizeable among males. Concerning depression, the protective effects of high adherence seemed independent of age, whereas the favorable actions of moderate adherence seemed to fade away with more advanced age. INTERPRETATION: Adherence to a Mediterranean diet may contribute to the prevention of a series of brain diseases; this may be of special value given the aging of Western societies.

Accumulating evidence supports that psoriasis may be a potential multisystem inflammatory disease associated with a range of co-morbidities showing an overlapping pathology and an important health impact such as metabolic diseases.   Psoriasis is associated with an increased risk of obesity, metabolic syndrome (Mets) and diabetes mellitus type 2 (t2DM), following a “dose-response” relationship from mild to severe psoriasis. Conversely, recent evidence from large prospective studies suggests that obesity constitutes a risk factor for psoriasis and psoriatic arthritis. Also, a dyslipidemic profile may precede psoriasis onset. Both obesity, Mets and psoriasis, characterized as chronic inflammatory states, stem from a shared underlying pathophysiology exhibiting common genetic predisposition and risk factors such as high caloric intake, physical inactivity and psychological stress. Excess weight may potentiate the inflammation of psoriasis through the deregulation of adipocytokines while, at the same time, it may help the development of Mets. Interestingly, recent translational data has shown that psoriasis, through increased T-helper inflammatory cytokines in skin and sera, may exert a plethora of effects on insulin regulation and lipid metabolism. Larger population-based prospective cohort and longitudinal studies are needed to unravel the association between psoriasis and metabolic co-morbidities. The recognition of the intricate complex interplay between psoriasis and metabolic co-morbidities may help dermatologists to be aware of associated metabolic co-morbidities in order to screen for metabolic diseases and manage holistically and effectively the psoriatic patient.

Medullary thyroid carcinoma (MTC) is a rare tumour which frequently occurs in the context of the multiple endocrine neoplasia syndromes, where it coexists with other usually benign tumours. The clinical picture varies and distant metastases are frequently present at diagnosis. Calcitonin levels are elevated in the presence of metastatic disease. Two MTC cases are presented, which had elevated postoperative calcitonin levels. Imaging revealed lung lesions which were originally attributed to metastatic disease from the MTC. However, at follow-up, these cases presented unusual features. The rapid increase in the lung lesions and the development of hypercalcaemia in the first patient suggested a second unrelated tumour. Biopsy of the lung lesion was compatible with lung adenocarcinoma. In the second patient, the appearance of a liver mass, although calcitonin levels remained stable, led to biopsy of the lesion: this was negative for calcitonin and compatible with metastatic lung adenocarcinoma. These MTC cases show that further malignancies may coexist with MTC and may obscure the clinical picture and influence the therapeutic decisions, especially in the case of metastatic disease. Features such as unusual imaging characteristics and the development of hypercalcemia, never encountered in MTC outside the MEN2 syndromes, as well as 'disproportionately' low calcitonin levels, incompatible with extensive metastatic disease, were the factors that led to further work-up. Both the cases subsequently proved to carry an unsuspected second malignancy. It is crucial to discriminate the metastatic lesion attributed to MTC from another coexisting primary malignancy, because different therapeutic strategies are needed for each setting. © 2013 Springer Science+Business Media New York.

Integrating amplifying media with metamaterials allows loss-free plasmonic operation and opens a route for controlling nanoscale quantum emitters.

The Aegean region of Greece hosts a series of crustal-scale extensional detachment systems that have accommodated the southward retreating Hellenic subduction zone. Extension has overprinted and dissected the Alpine nappe pile and locally exhumed Cordilleran-type metamorphic core complexes. On the island of Paros, a low-angle extensional detachment fault separates metamorphic footwall rocks from an unmetamorphosed sedimentary succession of the hanging wall. Basement orthogneisses were extensionally sheared in the footwall of the detachment until after 16. Ma (zircon U-Pb age of a slightly deformed granite), but pervasive ductile deformation had ceased by 7. Ma (zircon U-Pb age of an undeformed rhyolite dike that intrudes gneisses). Apatite and zircon (U-Th)/He ages from the gneisses confirm a period of cooling at rates >. 100. °C/Ma from 16 to 7. Ma. In the upper-plate, the basal sedimentary unit yields reset detrital apatite (U-Th)/He (DAHe) ages from 17 to 7. Ma and detrital zircon (U-Th)/He (DZHe) ages ranging from 270 to 18. Ma. DAHe ages from the stratigraphically higher fanglomerate units are reset to 10-7. Ma. The DZHe data have a primary thermal signature of 12-7. Ma, but preserve ages up to 113. Ma. The uppermost conglomerates exhibit completely reset DAHe ages of 15-9. Ma and reset DZHe ages from 10 to 8. Ma, with DZHe ages up to 104. Ma. Reset DAHe ages indicate late exposure of the footwall and constrain the depositional age of most sedimentary rocks on Paros to be from 14 to 7. Ma. Unreset DZHe ages preserve thermal signatures from the major Mesozoic-Tertiary tectonic events in the Aegean Region: [1] Cretaceous Pelagonian-type metamorphism; [2] Eocene peak HP metamorphism; and [3] Miocene Barrovian overprinting. Preservation of these signatures indicates long-term upper-plate recycling prior to syn-extensional deposition. The Paros supradetachment basin represents a classic inverted unroofing sequence deposited during progressive core complex exhumation in the Middle to Late Miocene. © 2012 Elsevier B.V.

This case control study aims to investigate the role of MMP-2 -1306C > T polymorphism as a potential risk factor and possible prognostic marker for breast cancer in a South European population. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy controls were recruited. MMP-2 -1306C > T polymorphism was genotyped; multivariate logistic regression as well as Cox regression analysis were performed. MMP-2 -1306C > T status was not associated with breast cancer risk either at the total sample or at the subanalyses on premenopausal and postmenopausal women. At the survival analysis, a trend towards a favorable association between MMP-2 -1306C > T allele and disease-free survival as well as overall survival was observed. Regarding subanalyses on ER-negative and ER-positive cases, the favorable association implicating MMP-2 -1306C > T allele was particularly evident among ER-positive cases; no significant associations emerged among ER-negative cases. MMP-2 -1306C > T polymorphism does not seem to be a risk factor for breast cancer in South European population; however, a trend towards a favorable association with survival has been observed. © 2013 Springer Science+Business Media Dordrecht.

Flood damages for residential and commercial/industrial areas can be direct and indirect. While direct damages are caused by physical contact of floodwater, indirect flood damages are caused through interruption of economic and social activities as a consequence of direct flood damages. Direct and indirect damages can be subdivided into primary and secondary categories as primary are the physical damages on the property and secondary damages are defined by the replacement costs. In this paper we are trying to estimate direct residential flood damages in a section of Kifissos drainage basin (Athens, Greece), taken into account the physical characteristics of the system as well as the landuse and predominant building types of the study area. Taken into account the results of this model each element of the urban environment has to be properly prepared and build capacity to cope with the current and future challenges.

In many cases, technological advances are based on artificial low-dimensional structures of heterogeneous constituents, thus called hybrids, that when come together they provide stand-alone entities that exhibit entirely different properties. Such hybrids are nowadays intensively studied since they are attractive for both basic research and oncoming practical applications. Here, we studied hybrids constituted of piezoelectric (PE) and ferromagnetic (FM) components in the form FM/PE/FM, ultimately aiming to provide means for the controlled modulation of the properties of the FM electrodes, originating from the strain imposed to them by the PE mediator when an electric field is applied. The PE component is in single crystal form, 0.71Pb(Mg1/3Nb2/3)O-3-0.29PbTiO(3) (PMN-PT), while the FM outer layers are Cobalt (Co) in thin film form. Detailed magnetization measurements performed under variation of the electric field applied to PMN-PT demonstrated the efficient modulation of the properties of the Co electrodes at low temperature (coercive field modulation up to 27% and saturation magnetization absolute modulation up to 4% at T = 10K for electric field not exceeding 6 kV/cm). The modulation degree faints upon increase of the temperature, evidencing that the thermal energy eventually dominates all other relevant energy scales. Candidate mechanisms are discussed for the explanation of these experimental observations. The results presented here demonstrate that commercially available materials can result in quantitatively noticeable effects. Thus, such elemental Co/PMN-PT/Co units can be used as a solid basis for the development of devices. (C) 2013 AIP Publishing LLC.

Here we examine the carbapenem and metronidazole resistance mechanisms of 640 Bacteroides strains reported in the 2008-2009 European antibiotic susceptibility survey. Of the 22 strains with elevated imipenem minimum inhibitory concentrations (≥4 μg/mL), 10 were cfiA-positive and out of these 5 carried activating insertion sequence (IS) elements in the upstream regions of the cfiA genes. However, resistant strains with cfiA genes but with no activating IS elements were found (n=2) as well as a resistant strain with no cfiA gene. In the former the resistance phenotypes by Etest were heterogeneous, whilst in the latter no carbapenemase production was seen; both mechanisms have been rarely observed, examined and characterised. Interestingly, few (n=3) nim-positive strains were found, including one metronidazole-resistant strain harbouring nimE activated by ISBf6, and two susceptible strains harbouring chromosomally located nim genes.

Background: Organisms are constantly exposed to physiological and environmental stresses and therefore require an efficient surveillance of genome and proteome quality in order to prevent disruption of homeostasis. Central to the intra- and extracellular proteome surveillance system are the molecular chaperones that contribute to both proteome maintenance and clearance. The conventional protein product of the apolipoprotein J/clusterin (CLU) gene is a heterodimeric secreted glycoprotein (also termed as sCLU) with a ubiquitous expression in human tissues. CLU exerts a small heat shock protein-like stress-induced chaperone activity and has been functionally implicated in numerous physiological processes as well as in ageing and most age-related diseases including tumorigenesis, neurodegeneration, and cardiovascular and metabolic syndromes. Objective: The CLU gene is differentially regulated by a wide variety of stimuli due to the combined presence of many distinct regulatory elements in its promoter that make it an extremely sensitive cellular biosensor of environmental and/or oxidative stress. Downstream to CLU gene induction, the CLU protein seems to actively intervene in pathological states of increased oxidative injury due to its chaperone-related property to inhibit protein aggregation and precipitation (a main feature of oxidant injury), as well as due to its reported distribution in both extra- and, most likely, intracellular compartments. Conclusion: On the basis of these findings, CLU has emerged as a unique regulator of cellular proteostasis. Nevertheless, it seemingly exerts a dual function in pathology. For instance, in normal cells and during early phases of carcinogenesis, CLU may inhibit tumor progression as it contributes to suppression of proteotoxic stress. In advanced neoplasia, however, it may offer a significant survival advantage in the tumor by suppressing many therapeutic stressors and enhancing metastasis. This review will critically present a synopsis of recent novel findings that relate to the function of this amazing molecule and support the notion that CLU is a biosensor of oxidative injury; a common link between ageing and all pathologies where CLU has been implicated. Potential future perspectives, implications and opportunities for translational research and the development of new therapies will be discussed.

Correct identification of the culprit allergen is an essential part of diagnosis and treatment in immunoglobulin E (IgE)-mediated allergic diseases. In recent years, molecular biology has made important advances facilitating such identification and overcoming some of the drawbacks of natural allergen extracts, which consist of mixtures of various proteins that may be allergenic or not, specific for the allergen source or widely distributed (panallergens). New technologies offer the opportunity for a more accurate component-resolved diagnosis, of benefit especially to polysensitized allergic patients. The basic elements of molecular diagnostics with potential relevance to immunotherapy prescription are reviewed here, with a focus on Southern European sensitization patterns to pollen allergens. We propose a basic algorithm regarding component-resolved diagnostic work-up for pollen allergen-specific immunotherapy candidates in Southern Europe; this and similar algorithms can form the basis of improved patient management, conceptually a 'Component-Resolved Allergy Management'.

Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the Maillard chemical process of non-enzymatic glycation of free amino groups of proteins, lipids and nucleic acids. This chemical modification of biomolecules is triggered by endogeneous hyperglycaemic or oxidative stress-related processes. Additionally, AGEs can derive from exogenous, mostly diet-related, sources. Considering that AGE accumulation in tissues correlates with ageing and is a hallmark in several age-related diseases it is not surprising that the role of AGEs in ageing and pathology has become increasingly evident. The receptor for AGEs (RAGE) is a single transmembrane protein being expressed in a wide variety of human cells. RAGE binds a broad repertoire of extracellular ligands and mediates responses to stress conditions by activating multiple signal transduction pathways being mostly responsible for acute and/or chronic inflammation. RAGE activation has been implicated in ageing as well as in a number of age-related diseases, including atherosclerosis, neurodegeneration, arthritis, stoke, diabetes and cancer. Here we present a synopsis of findings that relate to AGEs-reported implication in cell signalling pathways and ageing, as well as in pathology. Potential implications and opportunities for translational research and the development of new therapies are also discussed. © 2013 Informa UK, Ltd.

Pancreatic cancer is the fourth leading cause of cancer-related death. Most patients present with an advanced stage of disease that has a dismal outcome, with a median survival of approximately 6 months. Evidently, there is a clear need for the development of new agents with novel mechanisms of action in this disease. A number of biological agents modulating different signal transduction pathways are currently in clinical development, inhibiting angiogenesis and targeting epidermal growth factor receptor, cell cycle, matrix metalloproteinases, cyclooxygenase-2, mammalian target of rapamycin, or proteasome. This is the first systematic review of the literature to synthesize all available data coming from trials and evaluate the efficacy and safety of molecular targeted drugs in unresectable and metastatic pancreatic cancer. However, it should be stressed that although multiple agents have been tested, only 9 phase 3 trials have been conducted and one agent (erlotinib) has been approved by the Food and Drug Administration for use in clinical practice. As knowledge accumulates on the molecular mechanisms underlying carcinogenesis in the pancreas, the anticipated development and assessment of molecularly targeted agents may offer a promising perspective for a disease which, to date, remains incurable. Copyright © 2013 by Lippincott Williams & Wilkins.

We investigate the origin of high-energy emission in blazars within the context of the leptohadronic one-zone model. We find that γ-ray emission can be attributed to synchrotron radiation either from protons or from secondary leptons produced via photohadronic processes. These possibilities imply differences not only in the spectral energy distribution (SED) but also in the variability signatures, especially in the X- and γ-ray regime. Thus, the temporal behaviour of each leptohadronic scenario can be used to probe the particle population responsible for the high-energy emission as it can give extra information not available by spectral fits. In this work, we apply these ideas to the non-thermal emission of Mrk 421, which is one of the best monitored TeV blazars. We focus on the observations of 2001 March, since during that period Mrk 421 showed multiple flares that have been observed in detail both in X-rays and γ-rays. First, we obtain pre-flaring fits to the SED using the different types of leptohadronic scenarios. Then, we introduce random-walk-type, small-amplitude variations on the injection compactness or on the maximum energy of radiating particles and follow the subsequent response of the radiated photon spectrum. For each leptohadronic scenario, we calculate the X-ray and γ-ray fluxes and investigate their possible correlation. Whenever the `input' variations lead, apart from flux variability, also to spectral variability, we present the resulting relations between the spectral index and the flux, both in X-rays and γ-rays. We find that proton synchrotron models are favoured energetically but require fine tuning between electron and proton parameters to reproduce the observed quadratic behaviour between X-rays and TeV γ-rays. On the other hand, models based on pion decay can reproduce this behaviour in a much more natural way.

We investigate the origin of high-energy emission in blazars within the context of the leptohadronic one-zone model. We find that γ-ray emission can be attributed to synchrotron radiation either from protons or from secondary leptons produced via photohadronic processes. These possibilities imply differences not only in the spectral energy distribution (SED) but also in the variability signatures, especially in the X- and γ-ray regime. Thus, the temporal behaviour of each leptohadronic scenario can be used to probe the particle population responsible for the high-energy emission as it can give extra information not available by spectral fits. In this work, we apply these ideas to the non-thermal emission of Mrk 421, which is one of the best monitored TeV blazars. We focus on the observations of 2001 March, since during that period Mrk 421 showed multiple flares that have been observed in detail both in X-rays and γ-rays. First, we obtain pre-flaring fits to the SED using the different types of leptohadronic scenarios. Then, we introduce random-walk-type, small-amplitude variations on the injection compactness or on the maximum energy of radiating particles and follow the subsequent response of the radiated photon spectrum. For each leptohadronic scenario, we calculate the X-ray and γ-ray fluxes and investigate their possible correlation. Whenever the `input' variations lead, apart from flux variability, also to spectral variability, we present the resulting relations between the spectral index and the flux, both in X-rays and γ-rays. We find that proton synchrotron models are favoured energetically but require fine tuning between electron and proton parameters to reproduce the observed quadratic behaviour between X-rays and TeV γ-rays. On the other hand, models based on pion decay can reproduce this behaviour in a much more natural way.

Objective To assess the interaction of the MTHFR C677T polymorphism with changes in lipid and glucose metabolism effected by oral hormone replacement therapy (HRT) in postmenopausal women. Methods In this open-label, prospective, interventional study, parameters of lipid and glucose metabolism, as well as homocysteine, were assessed in 97 postmenopausal women at baseline and 1 year after the initiation of HRT. Participants were stratified into three subgroups, according to the MTHFR C677T polymorphism (wild-type: CC genotype; heterozygous: CT genotype; homozygous for the mutant variable: TT genotype). Results The TT genotype was associated with an elevation of total and low density lipoprotein (LDL) cholesterol, while CT and CC genotypes were associated with a reduction of total cholesterol and LDL cholesterol after 1 year of HRT (p = 0.032 for total cholesterol and p = 0.002 for LDL cholesterol). Women with the TT genotype had higher glucose levels in contrast to women with the CC genotype who had lower glucose levels after 1 year of HRT (p = 0.011). Additionally, CC carriers under HRT had a significant elevation of apolipoprotein A1 levels (p = 0.018), contrarily to CT and TT genotypes. Conclusion While HRT was associated with favorable changes in lipid and metabolic parameters in carriers of the CC genotype, this effect was not evident in carriers of the T allele. The MTHFR C677T polymorphism may modify the effect of HRT on lipid and metabolic parameters in postmenopausal women. © 2013 International Menopause Society.

A multiwalled carbon nanotube (MWCNT)-based electrochemical biosensor is developed for monitoring microcystin-LR (MC-LR), a toxic cyanobacterial toxin, in sources of drinking water supplies. The biosensor electrodes are fabricated using vertically well-aligned, dense, millimeter-long MWCNT arrays with a narrow size distribution, grown on patterned Si substrates by water-assisted chemical vapor deposition. High temperature thermal treatment (2500 °C) in an Ar atmosphere is used to enhance the crystallinity of the pristine materials, followed by electrochemical functionalization in alkaline solution to produce oxygen-containing functional groups on the MWCNT surface, thus providing the anchoring sites for linking molecules that allow the immobilization of MC-LR onto the MWCNT array electrodes. Addition of the monoclonal antibodies specific to MC-LR in the incubation solutions offers the required sensor specificity for toxin detection. The performance of the MWCNT array biosensor is evaluated using micro-Raman spectroscopy, including polarized Raman measurements, X-ray photoelectron spectroscopy, cyclic voltammetry, optical microscopy, and Faradaic electrochemical impedance spectroscopy. A linear dependence of the electron-transfer resistance on the MC-LR concentration is observed in the range of 0.05 to 20 μg L-1, which enables cyanotoxin monitoring well below the World Health Organization (WHO) provisional concentration limit of 1 μg L-1 for MC-LR in drinking water. An highly sensitive Faradaic electrochemical impedance biosensor for monitoring microcystin-LR (MC-LR) in sources of drinking water supplies is developed using millimeter-long multiwalled carbon nanotube (MWCNT) arrays grown by water-assisted chemical vapor deposition with vertical alignment. A linear sensing response shows a wide microcystin-LR concentration range that is below the World Health Organization (WHO) provisional guideline limit of 1 μg L-1 for MC-LR in drinking water. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

En este artículo se presentan la narración y la argumentación desde dos perspectivas:la lingüística y la cognitiva. Por un lado, nos detendremos en la narración y en laargumentación como tipos discursivos presentando las diferentes definiciones dadaspor los investigadores, así como los elementos característicos que las distinguen deotros tipos discursivos. Además, se exponen las diversas maneras en que las mismaspueden estar estructuradas. Por otro, las examinaremos desde la perspectiva cognitiva,es decir, como una modalidad de pensamiento y una habilidad cognitiva humana. Finprincipal del presente estudio es servir de herramienta didáctica a todos aquellosdocentes de LE que se vean involucrados en la enseñanza de los tipos textuales en laproducción escrita.

Πρόκειται για το επεξεργασμένο κείμενο ανακοίνωσης στο διεθνές συνέδριο «Heinrich von Kleist – Για τα 200 χρόνια από το θάνατό του», το οποίο διοργανώθηκε από το Τμήμα Γερμανικής Γλώσσας και Φιλολογίας του Πανεπιστημίου Αθηνών σε συνεργασία με το Εργαστήριο Μελέτης Ελληνογερμανικών Σχέσεων (Πανεπιστήμιο Αθηνών, Τμήμα Πολιτικής Επιστήμης και Δημόσιας Διοίκησης) και πραγματοποιήθηκε στην Αθήνα, στις 8, 9 και 10 Δεκεμβρίου 2011. Ως προς την επιλογή της θεματικής της, η τραγωδία Πενθεσίλεια (1808) του Χάινριχ φον Κλάιστ  (1777-1811) αποτελεί απόδειξη για τον προσανατολισμό του νέου συγγραφέα προς το αρχαίο δράμα και τον αρχαίο μύθο, κάτι καταρχήν απόλυτα σύμφωνο με τις επιταγές της εποχής. Ο Κλάιστ ανατρέχει σε ένα επεισόδιο από τον βίο και τις πράξεις του Αχιλλέα κατά τη διάρκεια της πολιορκίας της Τροίας, που αναφέρεται στη συνάντηση και μονομαχία του με την αμαζόνα Πενθεσίλεια, την οποία σκοτώνει. Στο κείμενό του ο Κλάιστ αντιστρέφει τους όρους, η Πενθεσίλεια είναι εκείνη που θα σκοτώσει τον Αχιλλέα, σε μια πράξη απελπισίας ως απόρροια της εσωτερικής της διαμάχης ανάμεσα στο νόμο των αμαζόνων και την επιθυμία της. Το δράμα δεν συνάδει διόλου με τις επιταγές του κλασικισμού της Βαϊμάρης σύμφωνα με τις οποίες η αρχαιότητα έχει αναχθεί σε ιδεώδες, σε πρότυπο αρμονίας και ανθρωπισμού και βασική κατηγορία του αισθητικού της προγράμματος. Ο Κλάιστ δεν εξωραΐζει την αφήγηση, αντίθετα παραθέτει σκηνές σκληρότητας και πάθους που απεικονίζουν τις εσωτερικές συγκρούσεις του νεωτερικού υποκειμένου, του υποκειμένου του Διαφωτισμού, που βιώνει ως μύθο την μέσω του ορθολογισμού χειραφέτησή του. Και ως προς τη μορφή ο Κλάιστ αποκλίνει από τα ειωθότα, παρουσιάζοντας μια τραγωδία διαρθρωμένη σε 24 σκηνές, σε συνεχή ροή, χωρίς κατανομή σε πράξεις, γεγονός που θεωρείται ότι παραπέμπει στις 24 ραψωδίες της Ιλιάδας. Δεν είναι το μόνο στοιχείο που διαφοροποιεί, ενδεχομένως, τον ειδολογικό χαρακτήρα του έργου. Η Πενθεσίλεια περιλαμβάνει εκτενείς αφηγήσεις, εφαρμόζοντας τεχνικές που ήδη το αρχαίο δράμα χρησιμοποιεί, οι οποίες, όπως και ο χορός, αποτελούν εν τέλει στοιχεία μάλλον επικού χαρακτήρα. Στην μελέτη αναδεικνύεται ο τρόπος προσέγγισης του Κλάιστ της μορφής του δράματος στο σύνολο έργο του, ενώ υποδεικνύεται και δοκιμάζεται ενδεικτικά η εφαρμογή στην ανάλυση της τραγωδίας Πενθεσίλεια ερμηνευτικών εργαλείων που προτείνει η σύγχρονη αφηγηματολογία, με στόχο αφενός τη συμβολή στον επίκαιρο διάλογο σχετικά με την αφηγηματική διάσταση του δράματος ως είδους και αφετέρου την ανάδειξη του ιδιότυπου «επικού» χαρακτήρα της Πενθεσίλειας, που αφηγείται την μήνιν της ηρωίδας.  

Covering: up to the end of June 2013 Ageing is a complex molecular process driven by diverse molecular pathways and biochemical events that are promoted by both environmental and genetic factors. Specifically, ageing is defined as a time-dependent decline of functional capacity and stress resistance, associated with increased chance of morbidity and mortality. These effects relate to age-related gradual accumulation of stressors that result in increasingly damaged biomolecules which eventually compromise cellular homeostasis. Nevertheless, the findings that genetic or diet interventions can increase lifespan in evolutionarily diverse organisms indicate that mortality can be postponed. Natural compounds represent an extraordinary inventory of high diversity structural scaffolds that can offer promising candidate chemical entities in the major healthcare challenge of increasing healthspan and/or delaying ageing. Herein, those natural compounds (either pure forms or extracts) that have been found to delay cellular senescence or in vivo ageing will be critically reviewed and summarized according to affected cellular signalling pathways. Moreover, the chemical structures of the identified natural compounds along with the profile of extracts related to their bioactive components will be presented and discussed. Finally, novel potential molecular targets for screening natural compounds for anti-ageing activity, as well as the idea that anti-ageing interventions represent a systemic approach that is also effective against age-related diseases will be discussed. © The Royal Society of Chemistry.

We use JHK photometry from the 2MASS catalog to construct color-magnitude diagrams and density profiles of intermediate age open clusters in the Galaxy, that appear to contain carbon stars within their radius. The clusters in the sample have not been extensively studied in the past, as they are often very low density as well as extended and therefore difficult to observe. We have used the most recent Padova isochrones (Bressan et al. 2013) to estimate the ages of the clusters.

Neudesin (also known as neuron derived neurotrophic factor, Nenf) is a scarcely studied putative non-canonical neurotrophic factor. In order to understand its function in the brain, we performed an extensive behavioral characterization (motor, emotional, and cognitive dimensions) of neudesin-null mice. The absence of neudesin leads to an anxious-like behavior as assessed in the elevated plus maze (EPM), light/dark box (LDB) and novelty suppressed feeding (NSF) tests, but not in the acoustic startle (AS) test. This anxious phenotype is associated with reduced dopaminergic input and impoverished dendritic arborizations in the dentate gyrus granule neurons of the ventral hippocampus. Interestingly, shorter dendrites are also observed in the bed nucleus of the stria terminalis (BNST) of neudesin-null mice. These findings lead us to suggest that neudesin is a novel relevant player in the maintenance of the anxiety circuitry.

Neudesin (also known as neuron derived neurotrophic factor, Nenf) is a scarcely studied putative non-canonical neurotrophic factor. In order to understand its function in the brain, we performed an extensive behavioral characterization (motor, emotional, and cognitive dimensions) of neudesin-null mice. The absence of neudesin leads to an anxious-like behavior as assessed in the elevated plus maze (EPM), light/dark box (LDB) and novelty suppressed feeding (NSF) tests, but not in the acoustic startle (AS) test. This anxious phenotype is associated with reduced dopaminergic input and impoverished dendritic arborizations in the dentate gyrus granule neurons of the ventral hippocampus. Interestingly, shorter dendrites are also observed in the bed nucleus of the stria terminalis (BNST) of neudesin-null mice. These findings lead us to suggest that neudesin is a novel relevant player in the maintenance of the anxiety circuitry.

We observed a newly discovered X-ray source int X-rays and in the optical to confirm its nature as a high mass X-ray binary. We analysed XMM-Newton and Swift X-ray data, along with optical observations with the ESO Faint Object Spectrograph, to investigate the spectral and temporal characteristics of the source. The XMM-Newton data show coherent X-ray pulsations while the spectra can be modelled with a combination of a power law plus a black body component. We performed optical spectroscopy from which we classify the companion star as a B0-1.5Ve star. The X-ray pulsations, the long-term x-ray variability and the properties of the optical counterpart confirms the the x-ray source as a new Be/X-ray binary pulsar in the LMC.

We report on integrated geomorphological, mineralogical, geochemical and biological investigations of the hydrothermal vent field located on the floor of the density-stratified acidic (pH   5) crater of the Kolumbo shallow-submarine arc-volcano, near Santorini. Kolumbo features rare geodynamic setting at convergent boundaries, where arc-volcanism and seafloor hydrothermal activity are occurring in thinned continental crust. Special focus is given to unique enrichments of polymetallic spires in Sb and Tl (±Hg, As, Au, Ag, Zn) indicating a new hybrid seafloor analogue of epithermal-to-volcanic-hosted-massive-sulphide deposits. Iron microbial-mat analyses reveal dominating ferrihydrite-type phases, and high-proportion of microbial sequences akin to "Nitrosopumilus maritimus", a mesophilic Thaumarchaeota strain capable of chemoautotrophic growth on hydrothermal ammonia and CO2. Our findings highlight that acidic shallow-submarine hydrothermal vents nourish marine ecosystems in which nitrifying Archaea are important and suggest ferrihydrite-type Fe3+-(hydrated)-oxyhydroxides in associated low-temperature iron mats are formed by anaerobic Fe2+-oxidation, dependent on microbially produced nitrate.

This paper concerns records of species that have extended their distribution in the Mediterranean Sea. The finding of the rare brackish angiosperm Althenia filiformis in the island of Cyprus is interesting since its insertion in the Red Data Book of the Flora of Cyprus is suggested. The following species enriched the flora or fauna lists of the relevant countries: the red alga Sebdenia dichotoma (Greece), the hydrachnid mite Pontarachna adriatica (Slovenia), and the thalassinid Gebiacantha talismani (Turkey). Several alien species were recorded in new Mediterranean localities. The record of the burrowing goby Trypauchen vagina in the North Levantine Sea (Turkish coast), suggests the start of spreading of this Lessepsian immigrant in the Mediterranean Sea. The findings of the following species indicate the extension of their occurrence in the Mediterranean Sea: the foraminifer Amphistegina lobifera (island of Zakynthos, Greece), the medusa Cassiopea andromeda (Syria), the copepod Centropages furcatus (Aegean Sea), the decapod shrimp Melicertus hathor (island of Kastellorizo, Greece), the crab Menoethius monoceros (Gulf of Tunis), the barnacles Balanus trigonus, Megabalanus tintinnabulum, Megabalanus coccopoma and the bivalves Chama asperella, Cucurbitula cymbium (Saronikos Gulf, Greece).

This paper concerns records of species that have extended their distribution in the Mediterranean Sea. The finding of the rare brackish angiosperm Althenia filiformis in the island of Cyprus is interesting since its insertion in the Red Data Book of the Flora of Cyprus is suggested. The following species enriched the flora or fauna lists of the relevant countries: the red alga Sebdenia dichotoma (Greece), the hydrachnid mite Pontarachna adriatica (Slovenia), and the thalassinid Gebiacantha talismani (Turkey). Several alien species were recorded in new Mediterranean localities. The record of the burrowing goby Trypauchen vagina in the North Levantine Sea (Turkish coast), suggests the start of spreading of this Lessepsian immigrant in the Mediterranean Sea. The findings of the following species indicate the extension of their occurrence in the Mediterranean Sea: the foraminifer Amphistegina lobifera (island of Zakynthos, Greece), the medusa Cassiopea andromeda (Syria), the copepod Centropages furcatus (Aegean Sea), the decapod shrimp Melicertus hathor (island of Kastellorizo, Greece), the crab Menoethius monoceros (Gulf of Tunis), the barnacles Balanus trigonus, Megabalanus tintinnabulum, Megabalanus coccopoma and the bivalves Chama asperella, Cucurbitula cymbium (Saronikos Gulf, Greece).

Several epidemiological studies have shown that the traditional Mediterranean diet is associated with a lower incidence of atherosclerosis, cardiovascular disease, neurodegenerative diseases, and certain kinds of cancer. These appreciable health-promoting properties have been partially correlated with the regular consumption of extra virgin olive oil as the principal source of fat. Olive oil is the most famous agricultural product in the Mediterranean, with a history as old as that region’s civilization. Olive fruits and olive oil not only are delicious but also have been considered as medicines since ancient times.

Group VIA calcium-independent phospholipase A2 (GVIA iPLA2) has recently emerged as an important pharmaceutical target. Selective and potent GVIA iPLA2 inhibitors can be used to study its role in various neurological disorders. In the current work, we explore the significance of the introduction of a substituent in previously reported potent GVIA iPLA2 inhibitors. 1,1,1,2,2-Pentafluoro-7-(4-methoxyphenyl)heptan-3-one (GK187) is the most potent and selective GVIA iPLA2 inhibitor ever reported with a XI(50) value of 0.0001, and with no significant inhibition against GIVA cPLA2 or GV sPLA2. We also compare the inhibition of two difluoromethyl ketones on GVIA iPLA2, GIVA cPLA2, and GV sPLA2.

In a monitoring observation of the central region of the Andromeda Galaxy (M 31) with the Ultra-violet/Optical Telescope (UVOT) on board the Swift satellite (ObsID 00035336102, starting 2013-05-27.15 UT), we detected a new UV transient (UVW1 filter, 181-321 nm). The source is located at RA 00h 42m 55.62s, Dec +41d 14' 12.3" (± 0.5", J2000, 90% confidence level). The following table lists the Swift ObsID, the MJD at the beginning of the exposure, UVW1 magnitudes (Vega system), and 1σ statistical uncertainties.

In the early 80s, the word automation was used in the clinical laboratory setting referring only to analyzers. But in late 80s and afterwards, automation found its way into all aspects of the diagnostic process, embracing not only the analytical but also the pre- and post-analytical phase. While laboratories in the eastern world, mainly Japan, paved the way for laboratory automation, US and European laboratories soon realized the benefits and were quick to follow. Clearly, automation and robotics will be a key survival tool in a very competitive and cost-concious healthcare market. What sets automation technology apart from so many other efficiency solutions are the dramatic savings that it brings to the clinical laboratory. Further standardization will assure the success of this revolutionary new technology. One of the main difficulties laboratory managers and personnel must deal with when studying solutions to reengineer a laboratory is familiarizing themselves with the multidisciplinary and technical terminology of this new and exciting field. The present review/glossary aims at giving an overview of the most frequently used terms within the scope of laboratory automation and to put laboratory automation on a sounder linguistic basis.

Organisms are constantly challenged by stressors and thus the maintenance of biomolecules functionality is essential for the assurance of cellular homeostasis. Proteins carry out the vast majority of cellular functions by mostly participating in multimeric protein assemblies that operate as protein machines. Cells have evolved a complex proteome quality control network for the rescue, when possible, or the degradation of damaged polypeptides. Nevertheless, despite these proteostasis ensuring mechanisms, new protein synthesis, and the replication-mediated dilution of proteome damage in mitotic cells, the gradual accumulation of stressors during aging (or due to lifestyle) results in increasingly damaged proteome. Non-enzymatic post-translational protein modifications mostly arise by unbalanced redox homeostasis and/or high glucose levels and may cause disruption of proteostasis as they can alter protein function. This outcome may then increase genomic instability due to reduced fidelity in processes like DNA replication or repair. Herein, we present a synopsis of the major non-enzymatic post-translation protein modifications and of the proteostasis network deregulation in carcinogenesis. We propose that activation of the proteostasis ensuring mechanisms in premalignant cells has tumor-preventive effects, whereas considering that over-activation of these mechanisms represents a hallmark of advanced tumors, their inhibition provides a strategy for the development of anti-tumor therapies.This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine. © 2013 Elsevier B.V.

A detailed and rigorous theoretical investigation of the optical properties of a generic three-dimensional chiral structure of plasma spheres, without and under the action of an external static uniform magnetic field, is presented. Corresponding photonic band diagrams in conjunction with relevant transmission spectra, calculated by the full electrodynamic layer-multiple-scattering method properly extended to the case of gyrotropic spherical scatterers, are discussed in the light of the theory of nonsymmorphic space groups. This analysis provides a consistent interpretation of some remarkable features and effects like Dirac points, polarization-dependent transmission, as well as band splitting and non-reciprocal optical response that emerge as a result of time-reversal-symmetry breaking, induced by the external static magnetic field, and the lack of space-inversion symmetry in the crystal.

We report on the occurrence and properties of photonic surface states in periodic structures of magnetized plasma nanospheres by means of rigorous calculations using the full-electrodynamic layer-multiple-scattering method, properly extended to treat gyrotropic spheres with arbitrarily oriented gyration vector. More specifically, dispersion diagrams of Tamm states at the (001) surface of a semi-infinite fcc crystal of plasma nanospheres and of guided modes of a square array of such spheres supported by a quartz substrate, without and under the action of an in-plane static uniform magnetic field, are analyzed and nonreciprocal optical response, which emerges as a result of the simultaneous lack of space-inversion and time-reversal symmetries, is demonstrated in the Voigt geometry.

When a healthy woman expresses concerns about her vulva, the doctor's response should be informed by clinical knowledge. For many doctors, accumulation of such knowledge would have begun with undergraduate teaching and medical textbooks. The aim of this study is to examine the information on female genital morphology in medical textbooks. A total of 59 gynaecology and anatomy textbooks were searched for information on the dimensions of vulval constitutent parts. No textbook gave measurements for all vulval structures. Vaginal length was reported in 21/59 textbooks, clitoral size in 15/59 and labia minora in 1/59. Where measurements appear, they suggest narrower ranges than recent reports. Information of vulval morphology is scanty and inaccurate in medical textbooks. The general lack of professional resources means that doctors may consciously or non-consciously rely upon personal experiences and popular culture to form their opinions, as do their patients. © 2013 Informa UK, Ltd.

Selected CCD photometry of the nova forwarded by E. Waagen, AAVSO: Aug. 13.955 UT, [10.2 (G. Murawski, Suwalki, Poland; V-band); 14.817, V = 6.5 (I. Sergey, Molodechno, Belarus); 14.872, V = 6.43 (P. Hallsten, Vasterhaninge, Sweden); 14.876, B = 6.43 (L. Corp, Rodez, France); 14.877, V = 6.11 (Corp); 14.878, R = 5.68 (Corp); 15.837, B = 5.35 (T. Wikander, Borlange, Sweden); 15.883, V = 5.13 (A. Sonka, Bucharest, Romania); 16.037, I = 4.60 (K. Gazeas, Athens, Greece); 16.035, R = 4.71 (Gazeas); 16.033, V = 4.80 (Gazeas); 16.031, B = 4.97 (Gazeas); 16.279, V = 4.44 (A. Oksanen, Muurame, Finland); 16.278, B = 4.82 (Oksanen);

DYRK kinases are involved in alternative pre-mRNA splicing as well as in neuropathological states such as Alzheimer’s disease and Down syndrome. In this study, we present the design, synthesis, and biological evaluation of indirubins as DYRK inhibitors with enhanced selectivity. Modifications of the bis-indole included polar or acidic functionalities at positions 5' and 6' and a bromine or a trifluoromethyl group at position 7, affording analogues that possess high activity and pronounced specificity. Compound 6i carrying a 5'-carboxylate moiety demonstrated the best inhibitory profile. A novel inverse binding mode, which forms the basis for the improved selectivity, was suggested by molecular modeling and confirmed by determining the crystal structure of DYRK2 in complex with 6i. Structure-activity relationships were further established, including a thermodynamic analysis of binding site water molecules, offering a structural explanation for the selective DYRK inhibition. © 2012 American Chemical Society.

Blending of chewing gums of different colours is used in the clinical setting, as a simple and reliable means for the assessment of chewing efficiency. However, the available software is difficult to use in an everyday clinical setting, and there is no possibility of automated classification of the patient's chewing ability in a graph, to facilitate visualisation of the results and to evaluate potential chewing difficulties. The aims of this study were to test the validity of ViewGum - a novel image analysis software for the evaluation of boli derived from a two-colour mixing ability test - and to establish a baseline graph for the representation of the masticatory efficiency in a healthy population. Image analysis demonstrated significant hue variation decrease as the number of chewing cycles increased, indicating a higher degree of colour mixture. Standard deviation of hue (SDHue) was significantly different between all chewing cycles. Regression of the log-transformed values of the medians of SDHue on the number of chewing cycles showed a high statistically significant correlation (r² = 0.94, P < 0.01). ViewGum eliminates drawbacks of previous two-colour chewing gum test methods by the simplicity of its application. The newly developed ViewGum software provides speed, ease of use and immediate extraction of clinically useful conclusions to the already established method of chewing efficiency evaluation and is a valid adjunct for the evaluation of masticatory efficiency with two-colour chewing gum.

Worldwide, breast cancer (BC) represents the most common type of non-skin human malignancy and the second leading cause of cancer-related deaths amid women in Western countries. Obesity and its metabolic complications have rapidly become major global health issues and are associated with increased risk for cancer, especially BC in postmenopausal women. Adipose tissue is considered as a genuine endocrine organ secreting a variety of bioactive adipokines, such as leptin, adiponectin, resistin and nicotinamide phosphoribosyl-transferase/visfatin. Recent evidence has indicated that the constellation of obesity, insulin resistance and adipokines is associated with the risk and prognosis of postmenopausal BC. Direct evidence is growing rapidly supporting the stimulating and/or inhibiting role of adipokines in the process of development and progression of BC. Adipokines could exert their effects on the normal and neoplastic mammary tissue by endocrine, paracrine and autocrine mechanisms. Recent studies support a role of adipokines as novel risk factors and potential diagnostic and prognostic biomarkers in BC. This editorial aims at providing important insights into the potential pathophysiological mechanisms linking adipokines to the etiopathogenesis of BC in the context of a dysfunctional adipose tissue and insulin resistance in obesity. A better understanding of these mechanisms may be important for the development of attractive preventive and therapeutic strategies against obesity-related breast malignancy.

To date, an obesity/asthma link is well defined in adults; however, the nature of such a link is obscure in children, partly due to Body Mass Index (BMI) limitations as a surrogate fat mass marker in childhood. We thus opted to investigate the association of adiposity with asthma in children of different ages, using several indices to assess fat mass.|Wheeze ever/in the last 12 months (current) and physician-diagnosed asthma were retrospectively reported via questionnaire by the parents of 3641 children, participating in two cross-sectional studies: 1626 children aged 2-5 (the Genesis Study) and 2015 children aged 9-13 (the Healthy Growth Study). Perinatal data were recorded from the children's medical records or reported by parents. Anthropometric measurements (i.e., BMI, waist/hip circumference, biceps/triceps/subscapular/suprailiac skinfold thickness) were conducted in both cohorts; bioelectric impedance analysis (BIA) was conducted only in preadolescent children.|In children aged 2-5, asthma was positively correlated with conicity index, waist/hip circumference, waist-to-height ratio, skinfold thickness, and skinfold-derived percentage fat mass (P < 0.05) but not BMI or BMI-defined overweight/obesity, after adjusting for several confounders. In children aged 9-13, asthma was positively associated with conicity index, waist circumference, waist-to-height ratio, skinfold thickness, skinfold-derived percentage fat mass, BIA-derived percentage fat mass, BMI, and BMI-defined overweight/obesity, following adjustment (P < 0.05). Current/ever wheeze was not consistently associated with fat mass in either population.|Fat mass is positively linked to asthma in both 2-5 and 9-13 age spans. However, the failure of BMI to correlate with preschool asthma suggests its potential inefficiency in asthma studies at this age range.

The present study, deals with the 24-hour prognosis of the outdoor biometeorological conditions in an urban monitoring site within the Greater Athens area, Greece. For this purpose, artificial neural networks (ANNs) modelling techniques are applied in order to predict the maximum and the minimum value of the physiologically equivalent temperature (PET) one day ahead as well as the persistence of the hours with extreme human biometeorological conditions. The findings of the analysis showed that extreme heat stress appears to be 10.0% of the examined hours within the warm period of the year, against extreme cold stress for 22.8% of the hours during the cold period of the year. Finally, human thermal comfort sensation accounts for 81.8% of the hours during the year. Concerning the PET prognosis, ANNs have a remarkable forecasting ability to predict the extreme daily PET values one day ahead, as well as the persistence of extreme conditions during the day, at a significant statistical level of P < 0.01. © 2013 K. P. Moustris et al.

This article studies the dynamic control of arrivals of multiple job classes in N-stage production systems with finite buffers and blocking after service. A model with multiple processing stages in series is formulated as a Markov decision process and a state definition from the queueing analysis literature is used to simplify the state-space description. This allows several fundamental admission control results from M/M/N and M/M/N/N queueing models as well as tandem models without blocking to be extended to tandem systems with blocking. Specifically, it is shown that the net benefit of admitting a job declines monotonically with the system congestion; thus the decision to admit any job class is based on threshold values of the number of jobs present in the system. Furthermore, conditions under which a job class is always or never admitted, regardless of the state, are derived. The interaction of blocking and admission control is explored by analyzing the effect of blocking on the optimal admission policy and profit. The article concludes with analyses of why extensions including loss and abandonment cannot sustain the monotonicity properties and two surrogate admission rules that may be used in practice but do not account for the blocking effect. © 2013 Taylor & Francis Group, LLC.

Chios mastic gum, the resin obtained as an exudate from the trunk and branches of Pistacia lentiscus L var. chia, is used extensively as a constituent of herbal drugs or functional foods. The oral absorption of its major constituents still remains unclear. In the context of identifying the features of mastic gum that are responsible for either therapeutic effects or effects of nutritional value, a methodology based on high-performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS) was developed and applied for the quantification of mastic gum triterpenic acids, 24Z-isomasticadienonic acid (IMNA), and 24Z-isomasticadienolic acid (IMLA) in mouse plasma. The specific compounds were selected based on their biological activity and potential against Helicobacter pylori. Concentrations were determined simultaneously in mouse plasma after oral administration of mastic gum or total mastic extract without polymer (TMEWP) in order to evaluate the role of the natural polymer, poly-β-myrcene, in the absorption process. Following TMEWP administration in mice, circulating IMNA and IMLA plasma levels were significantly higher (approximately 10-fold) in comparison to IMNA and IMLA plasma levels following total mastic gum administration (CMG), suggesting that the polymer plays a critical role in the absorption process. More specifically following TMEWP administration, Cmax plasma values were 3300 ± 859 ng/mL for IMNA and 163 ± 58 ng/mL for IMLA. In comparison, following CMG administration, Cmax plasma values were 329 ± 57 ng/mL for IMNA and 28 ± 8 ng/mL for IMLA.The methodological approaches presented in this study, along with the findings, offer valuable information on the availability of bioactive components following ingestion of mastic and facilitate the uses of mastic either as an ingredient of functional foods or as a herbal drug. © Georg Thieme Verlag KG.

Using density functional theory calculations, ultrathin films of SrVO3(d(1)) and SrCrO3(d(2)) on SrTiO3 substrates have been studied as possible multiferroics. Although both are metallic in the bulk limit, they are found to be insulating as a result of orbital ordering driven by lattice distortions at the ultrathin limit. While the distortions in SrVO3 have a first-order Jahn-Teller origin, those in SrCrO3 are ferroelectric in nature. This route to ferroelectricity results in polarizations comparable with conventional ferroelectrics.

In this work, we prepared oriented mesoporous thin films of silica on various solid substrates using the pluronic block copolymer P123 as a template. We attempted to insert guest iron oxide (FexOy) nanoparticles into these films by two different methods: (a) by co-precipitation-where iron precursors are introduced in the synthesis sol before deposition of the silica film-and subsequent oxide production during the film calcination step; (b) by preparing and calcining the silica films first then impregnating them with the iron precursor, obtaining the iron oxide nanoparticles by a second calcination step. We have examined the structural effects of the guest nanoparticles on the silica film structures using grazing incidence X-ray scattering (GISAXS), high-resolution transmission electron spectroscopy (HRTEM), spectroscopic ellipsometry, X-ray photoelectron spectroscopy (XPS), and Raman microscopy. Formation of nanoparticles by co-precipitation may induce substantial changes in the film structure leading, in our adopted process, to the appearance of lamellar ordering in the calcination stage. On the contrary, impregnation-based approaches perturb the film structures much more weakly, but are also less efficient in filling the pores with nanoparticles. © 2013 by the authors.

Background: Tumour-associated lymphocytes (TALs) present in effusions of ovarian cancer patients exhibit impaired activities, due to the immunosuppressive environment of the ascites. Means to enhance their cytotoxicity against autologous tumour cells are of clinical importance. The immunomodulator prothymosin alpha (proTα) increases the specific lysis of tumour cells by activated CD8+ T-lymphocytes and its immunoreactivity is exerted by the carboxy-terminal decapeptide, proTα(100-109). These two molecules were studied on TALs in vitro, and in SCID mice bearing human ovarian tumours. Methods: TALs and tumour cells were isolated from 41 ovarian cancer patients and co-cultured in the presence of proTα or proTα(100-109). The cytotoxicity of peptide-stimulated TALs was tested against autologous tumour cells and K562. Ex vivo peptide-stimulated TALs from three patients were adoptively transferred intraperitoneally in SCID mice, previously inoculated with each patient's autologous tumour cells. Results: ProTα and its immunoreactive peptide proTα(100-109), enhanced the cytotoxic activity of TALs against autologous tumour cells in vitro, but marginally affected the lysis of K562. The effect of proTα and proTα(100-109) was higher after 7-14 days of stimulation, whereas TAL cytotoxicity was significantly decreased after 21 days. Mice administered TALs, ex vivo activated with proTα or proTα(100-109) for 7 days, showed a relatively lower tumour increase rate and a prolongation of their survial, compared to controls. Conclusion: Our data demonstrate that, in the presence of tumour antigens, proTα and proTα(100-109) enhance the depressed cytotoxicity of TALs against autologous tumour cells in vitro and retard tumour growth in vivo. © 2013 Elsevier Ltd. All rights reserved.

BACKGROUND: SAHA syndrome is characterized by the tetrad: seborrhea, acne, hirsutism, and androgenetic alopecia. No previous study has examined the prevalence of glucose abnormalities in ovarian SAHA and explored whether it may be an independent risk factor for glucose abnormalities. OBJECTIVE: In a prospective controlled study, we investigated the spectrum of glucose abnormalities in ovarian SAHA and explored whether it is associated with a more insulin-resistant profile. METHODS: In all, 316 patients with a diagnosis of polycystic ovary syndrome (PCOS) (56 with SAHA) and 102 age-matched healthy women were examined and underwent a 2-hour oral glucose tolerance test. Serum glucose homeostasis parameters, hormones, and adipokines were determined. RESULTS: SAHA prevalence was 17.7% in patients with PCOS and predominance of the severe PCOS phenotype. Ovarian SAHA was independently associated with a more insulin-resistant profile (higher homeostatic model assessment of insulin resistance score, lower quantitative insulin sensitivity check index [QUICKI] and MATSUDA indices, and relative hypoadiponectinemia), and represented an independent risk factor for glucose abnormalities regardless of anthropometric features, age, and PCOS phenotype. LIMITATION: There was no performance of skin biopsies. CONCLUSION: The prompt recognition of SAHA syndrome in women with PCOS permits an earlier diagnosis and surveillance of metabolic abnormalities, especially in Mediterranean PCOS population exhibiting a lower prevalence of glucose abnormalities.

OBJECTIVE: To examine whether both OX40 and its ligand OX40L are expressed in idiopathic inflammatory myopathies and to investigate the types of inflammatory cells expressing OX40L. STUDY DESIGN: Immunohistochemistry was performed in limb muscle specimens from dermatomyositis, polymyositis and inclusion body myositis patients to analyze the expression of OX40 and its ligand OX40L. Double immunofluorescence labeling was performed to clarify the phenotype of inflammatory cells expressing OX40L. RESULTS: OX40 and OX40L expressing cells were observed in all subsets of inflammatory myopathies following a similar pattern of distribution mainly in the perimysium. In polymyositis and inclusion body myositis inflammatory cells expressing the receptors invaded non-necrotic muscle fibers. OX40L expression was also found in endothelial blood cells in all dermatomyositis and some polymyositis specimens. In all subsets of inflammatory myopathies OX40L was expressed by T cells (CD4+ and CD8+), macrophages (CD68+), B cells (CD20+) and myeloid dendritic cells (BDCA1+). Plasmacytoid dendritic cells (BDCA2+) expressing OX40L were found only in dermatomyositis and polymyositis. CONCLUSION: The simultaneous expression of both OX40 and its ligand OX40L in idiopathic inflammatory myopathies suggests that they might participate in disease pathogenesis. Expression of OX40L by different types of cells within the inflamed muscle implies that OX40-OX40L interaction may contribute in disease mechanisms through different pathways.

The results of a comparison between monthly mean ozone column variations calculated from the chemical transport model Oslo CTM2 and those derived from solar backscatter ultraviolet (SBUV) satellite observations are presented for the period 1998-2009. Monthly mean total ozone derived from improved model simulations were used to compute monthly zonal means over 10 latitude zones over the northern and southern hemispheres. Ozone column variations from Oslo CTM2 are highly correlated with SBUV retrievals at all latitude zones. Equatorial zonal winds at 30 hPa were used as index to study the impact of quasi-biennial oscillation (QBO) on ozone. Correlations between modeled ozone and the QBO were found to be the order of +0.8 in the tropics. The impact of QBO was most pronounced at equatorial latitudes with amplitudes of +4 to -4 %. Seasonal variations in surface ozone and tropospheric ozone column calculated by the model are also presented. © 2013 Springer Science+Business Media Dordrecht.

Le présent article, qui s’appuie essentiellement sur une documentation photographique non publiée, étudie le fonds photographique de la Société de Géographie de Paris (SGP) analysant des clichés datant de la fin du XIXe siècle et du début du XXe siècle. A une époque où la photographie sert de documentation et de moyen d’éducation, la SGP a inauguré une politique de collecte de photographies. Conservé actuellement à la BnF, son fonds photographique comprend des clichés commerciaux, que les voyageurs achétaient au cours de leurs pérégrinations, des clichés pris lors des missions scientifiques ainsi que des clichés d’amateurs, que les membres de SGP lui offraient. Associant la qualité esthétique à la valeur documentaire et historique, le fonds photographique de la SGP, qui perpétue souvent l’image stéréotypée de l’Orient, représente les différents aspects de l’Empire ottoman permettant parfois la reconstitution des étapes des pérégrinations des voyageurs. De plus, le fonds photographique, qui est caractérisé par une variété thématique, est révélateur de l’intérêt de l’Empire ottoman pour la gestion de son image dans le cadre de la propagande politique. Finalement, le fonds photographique du SGP constitue un exemple caractéristique du rôle et de la réception de la photographie comme documentation.

""Saint Neophytos the Recluse (12th cent.) is the writer of Tυπικὴ Διαθήκη (ΤΔ), the first Typikon (Charter of foundation) of the monastery he founded in Paphos. Each particular edition of and research on saint Neophytos’ TΔ has its own value. The autobiographical passages of ΤΔ provide valuable pieces of information about the saint᾽s life and personality. Most researchers agree on specific elements such as the fact that the saints’ hometown was located in the wider region of Lefkara, that his parents had signed an engagement contract against his will, etc. Kyprianos (1779) claimed that Neophytos had been married for a while before he assumed the monastic habit; however, such a claim is proved unfounded. There is an open discussion among the researchers concerning the exact time when Neophytos wrote TΔ. Some claim that he wrote the first TΔ in 1177, 18 years after 1159, the year of his installation in the cave of Enkleistra (place of seclusion). They support that the number 8 that exists in the manuscript instead of the correct 18 is due to false writing. Our view differs. The investigation of the autobiographical passages in all of his works and the note in the second and final TΔ that Bakchos, bishop of Paphos, ratified the first TΔ, in relation to Neophytos’ statement that the first TΔ claimed absolute  indigence of the Monastery, a claim that ceased to exist during the Latin occupation of the island (after 1191), as well as the morphological observation on the text that the word «cave» was replaced by the word «Enkleistra» from the point of reference to Basil Kinnamos as bishop of Paphos provide valuable evidence. All these led to the conclusion that the immurement of Neophytos took place in 1167, long after his initial installation in the cave (1159). Therefore the writing of the first TΔ took place eight years later, as is faultlessly mentioned in the manuscript, that is, in 1175. Among others, a new opinion is supported in relation to the 5th chapter of TΔ. Most researchers believe that according to this chapter, Neophytos made a trip to Jerusalem and found wood of the Holy Cross. We argue that this «holy trip» was not real, but the saint implies his persistent request in his prayer, so as to receive a piece of the Holy Cross from a visitor, request which was finally granted by God.""

Rhinitis is a common problem in childhood and adolescence and impacts negatively on physical, social and psychological well-being. This position paper, prepared by the European Academy of Allergy and Clinical Immunology Taskforce on Rhinitis in Children, aims to provide evidence-based recommendations for the diagnosis and therapy of paediatric rhinitis. Rhinitis is characterized by at least two nasal symptoms: rhinorrhoea, blockage, sneezing or itching. It is classified as allergic rhinitis, infectious rhinitis and nonallergic, noninfectious rhinitis. Similar symptoms may occur with other conditions such as adenoidal hypertrophy, septal deviation and nasal polyps. Examination by anterior rhinoscopy and allergy tests may help to substantiate a diagnosis of allergic rhinitis. Avoidance of relevant allergens may be helpful for allergic rhinitis (AR). Oral and intranasal antihistamines and nasal corticosteroids are both appropriate for first-line AR treatment although the latter are more effective. Once-daily forms of corticosteroids are preferred given their improved safety profile. Potentially useful add-on therapies for AR include oral leukotriene receptor antagonists, short bursts of a nasal decongestant, saline douches and nasal anticholinergics. Allergen-specific immunotherapy is helpful in IgE-mediated AR and may prevent the progression of allergic disease. There are still a number of areas that need to be clarified in the management of rhinitis in children and adolescents.

The history of Mediterranean vegetation can be outlined using pollen grains contained in lacustrine, marine and other sediments. These sediments have recorded very important vegetation changes during recent geological times. For example, during the last 6 Ma (million years), the effects of different events acting at regional (e.g. the Messinian salinity crisis between 5.96 Ma and 5.33 Ma) and global (expansion of the Arctic ice at ca 2.6 Ma) scales produced a progressive decrease and final disappearance of tropical and subtropical taxa. However, prior to the start of the Quaternary the Mediterranean flora still included a consistent number of tropical and subtropical arboreal taxa accompanying deciduous and partly evergreen trees that have persisted until today. The most important features of the vegetation history of the Quaternary consist in the fact that vegetation adapted to climate changes due to changes in orbital cyclicity, alternating between glacial and interglacial periods. The more widespread vegetation types were steppe and grassland formations during the dry and cold glacial periods whereas either deciduous or evergreen forests were characteristic of interglacial periods. These cold-dry to warmhumid climate cycles became more and more intense towards the present. During the second half of the present interglacial, after the mid-Holocene, joint actions of increasing dryness, climate oscillations and human impact led to the present day Mediterranean plant landscape. It is however not clear how far the causation of this spread of evergreen taxa was climatic or human. One of the most exciting challenges is the prediction of the future course of Mediterranean vegetation. In this perspective a consistent help, not fully explored yet, can be found in aeropalynology, recording the pollen transported in the air. Together with modern surface samples, these data act as modern analogues. Though it probably does not represent the same past vegetational composition, the current pollen rain is the only basic reference on which our comparative approach can rely. Present trends are interpreted and future scenarios can be hypothesized just using a combination of aero- and archaeo-/palaeo-palynological approaches.

Populations of many countries are becoming increasingly overweight and obese, driven largely by excessive calorie intake and reduced physical activity; greater body mass is accompanied by epidemic levels of comorbid metabolic diseases. At the same time, individuals are living longer. The combination of aging and the increased prevalence of metabolic disease is associated with increases in aging-related comorbid diseases such as Alzheimer's disease, cerebrovascular dementia, and sarcopenia. Here, correlative and causal links between diseases of overnutrition and diseases of aging and cognition are explored.

High-power high-frequency gyrotrons are required for several applications, including plasma heating, current drive, and plasmas stabilization for controlled thermonuclear fusion. Despite the use of dumping dielectric material in these gyrotrons, parasitic oscillations often appear, which significantly affect their operation and efficiency. In this paper, we perform an extended parametric study on the effect of the beam-tunnel characteristics, i.e., the outer radius of the inner waveguide and the width of the grooves, as well as the lossy material properties and the beam-radial position on the dumping of these oscillations.

The strong epidemiologic and pathophysiologic link between allergic rhinitis (AR) and asthma has led to the concept of 'united airways disease' or 'respiratory allergy', implying that allergy, in its widest sense, underlies this clinical syndrome. Progression from AR to asthma is frequent and part of the 'atopic march'. Since pediatric immune responses are more adaptable and therefore may be more amenable to treatment, interventions at early childhood are characterized by a higher chance to affect the natural history of respiratory allergy. Although current treatments are quite effective in alleviating respiratory allergy symptoms, it has proven much more difficult to confirm any influence on the progression of the disease. Much more promising is the field of specific allergen immunotherapy, where current evidence, although not yet of ideal robustness, points towards a disease-modifying effect. In addition, newer or emerging, possibly more effective or more targeted interventions are promising in the preventive sense.

Purpose This final analysis of the phase III VISTA trial (Velcade As Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone) was conducted to determine whether the overall survival (OS) benefit with bortezomib-melphalan-prednisone (VMP) versus melphalanprednisone (MP) in patients with myeloma who were ineligible for transplantation was maintained after 5 years of follow-up and to explore the risk of second primary malignancies. Patients and Methods In all, 682 patients received up to nine 6-week cycles of VMP or MP and were then observed every 12 weeks or less. Data on second primary malignancies were collected by individual patient inquiries at all sites from 655 patients. Results After median follow-up of 60.1 months (range, 0 to 74 months), there was a 31% reduced risk of death with VMP versus MP (hazard ratio [HR], 0.695; P < .001; median OS 56.4 v 43.1 months). OS benefit with VMP was seen across prespecified patient subgroups (age ≥ 75 years, stage III myeloma, creatinine clearance < 60 mL/min). Sixty-three percent of VMP patients and 73% of MP patients had received subsequent therapy. Time to next therapy (median, 30.7 v 20.5 months; HR, 0.557; P < .001) was longer with VMP than with MP. Among patients who received subsequent therapies, survival from start of subsequent therapy was similar following VMP (median, 28.1 months) or MP (median, 26.8 months; HR, 0.914). Following VMP/MP, incidence proportions of hematologic malignancies (1%/1%) and solid tumors (5%/3%) and exposure-adjusted incidence rates (0.017/0.013 per patient-year) were similar and were consistent with background rates. Conclusion VMP resulted in a significant reduction in risk of death versus MP that was maintained after 5 years' follow-up and despite substantial use of novel-agent-based salvage therapies. There is no emerging safety signal for second primary malignancies following VMP. © 2012 by American Society of Clinical Oncology.

Pertuzumab is a monoclonal antibody that represents the first among a new class of agents known as human epidermal growth factor receptor (HER) dimerization inhibitors. This is the first systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to synthesize all available data of pertuzumab in breast cancer. The search strategy retrieved 11 studies that evaluated pertuzumab. One study was conducted in the neoadjuvant setting (417 patients), whereas all the others dealt with patients with recurrent, metastatic, or refractory disease (1023 patients). Six studies were conducted in HER2+ breast cancer population (1354 patients), whereas 5 studies (86 patients) were conducted in HER2- (or unknown HER2 status) disease. Pertuzumab is the most recent agent approved by the US Food and Drug Administration in combination with trastuzumab and docetaxel for the treatment of patients with HER2+ metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. This approval has been based on data from a phase III Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study. The antitumor activity with the significant reduction in the risk of progression or death, as reflected upon the increase of 6.1 months in median progression-free survival, indicates that pertuzumab may provide an avenue for achieving additional benefit for patients with HER2+. Moreover, pertuzumab seems to have a putative role in the management of patients with HER2 who are resistant to trastuzumab. The promising role of pertuzumab in the neoadjuvant and adjuvant settings remains to be further investigated and established in the future. © 2013 Elsevier Inc. All rights reserved.

Το βιβλίο διατυπώνει θεμελιώδη ερωτήματα για την παιδεία και την πολιτική: Ποιος επωφελείται από το εκπαιδευτικό σύστημα και τους ισχύοντες εκπαιδευτικούς µηχανισµούς, και ποιων συμφέροντα εξυπηρετούν οι υπάρχουσες παιδαγωγικές πρακτικές; Ποια είναι η σχέση μεταξύ των παιδαγωγικών πρακτικών και της εκπαίδευσης ως διαδικασίας αναπαραγωγής του συστήματος της κυρίαρχης τάξης; Συμβάλλει στη διαμόρφωση εναλλακτικών προτάσεων από την πλευρά του κινήματος των εκπαιδευτικών που αμφισβητεί τον πυρήνα της καπιταλιστικής εκπαίδευσης, αποδεικνύοντας ότι μια άλλη εκπαίδευση και μια άλλη κοινωνία είναι εφικτές. Αρθρώνει έναν προγραµµατικό λόγο όπου η φωνή των φτωχών κοινωνικών στρωμάτων, των γυναικών, των ατόμων µε ειδικές ανάγκες, των μεταναστών και γενικότερα των κοινωνικών μειονοτήτων έχει ισχυρή θέση στον εκπαιδευτικό σχεδιασμό. Το βιβλίο αυτό αποτελεί ξεχωριστή συμβολή στο ρεύμα που ο McLaren ονόμασε Επαναστατική Κριτική Παιδαγωγική, ως απάντηση στη συνεχή, και τις περισσότερες φορές επιτυχή, προσπάθεια χειραγώγησης της Κριτικής Παιδαγωγικής.

Ποιος ήταν στ’ αλήθεια ο Δανός αρχαιολόγος, θεολόγος και φιλόλογος Peter Oluf Brønsted (1780-1842), ένας πρωτοπόρος φιλέλληνας ή, μήπως ένας άλλος Elgin; Ο Brønsted έφτασε στην Ελλάδα τον Ιούλιο του 1810, πραγματοποιώντας την πρώτη, ουσιαστικά, επίσκεψη Δανού περιηγητή στην χώρα. Η αναφορά, ωστόσο, των ονομάτων της πενταμελούς ομάδας που ταξίδεψε μαζί του, αποτελούμενη από το Δανό φιλόλογο και μουσικό Georg H.C. Koës, τους Γερμανούς, αρχιτέκτονα Carl Haller von Hallerstein από τη Νυρεμβέργη και ζωγράφο Jakob Linckh από τη Βυρτεμβέργη, και, τέλος, από τον Εσθονό βαρώνο Otto Magnus von Stackelderg, είναι αρκετή για να κατανοήσει κανείς τον αληθινό σκοπό της επίσκεψης αυτών των «πνευματικών» ανθρώπων της Δύσης. Ο von Hallerstein υπήρξε Πράκτορας του διαδόχου της Βαυαρίας Λουδοβίκου, με αποστολή του στην Ελλάδα τη συγκέντρωση αρχαιοτήτων, και με εντολή να αγοράσει όλες τις κεφαλές των αλόγων που είχαν απομείνει στο ανατολικό αέτωμα του Παρθενώνα και μια Καρυάτιδα. Ο ίδιος θα πραγματοποιήσει ανασκαφές στα Μέγαρα και την Ιθάκη και θα αγοράσει το αρχαίο θέατρο της Μήλου για λογαριασμό του Λουδοβίκου. Αλλά και οι τρεις άλλοι της παρέας, ο von Stackelberg, ο Linkh και ο Koës, κατηγορήθηκαν για κλοπή των αρχαίων ελληνικών ευρημάτων και για κερδοσκοπία. Η χρονιά που κατέφθασε ο Brønsted στην Ελλάδα, το 1810, ήταν η χρονιά κατά την οποία ο Άγγλος λόρδος Elgin (: Thomas Bruce) φόρτωσε το τρίτο μέρος της λείας του με το πολεμικό πλοίο «Ύδρα». Η λεηλασία των μνημείων γενικεύτηκε στις αρχές του ΙΘ΄ αιώνα. H δήθεν «αρχαιολογική» έρευνα ματατράπηκε σε ληστρική επιχείρηση, με ολέθριες συνέπειες για τα μνημεία και τα έργα τέχνης. Η πολυεθνική εταιρία αρχαιοκαπήλων που είχε συγκροτηθεί από το 1807 για ανασκαφές σε ελληνικούς αρχαιολογικούς χώρους και πώληση ευρημάτων στην ευρωπαϊκή αγορά, είχε ως μέλη της την αφρόκρεμα της ευρωπαϊκής ελίτ. Συνεργάτες της, μεταξύ άλλων, ήταν ο Γάλλος αρχαιολόγος Louis François Fauvel, πρόξενος της Γαλλίας στην Αθήνα, ο επίσης αρχαιοκάπηλος Γερμανός Georg Christian Gropius, κατοπινός πρόξενος της Αυστρίας και ο Άγγλος Charles Robert Cockerell. Η εργασία παρακολουθεί τις επαφές του Brønsted με την Υψηλή Πύλη, τις προσωπικές του επαφές με πρόσωπα υψηλά ιστάμενα, τις ανασκαφές που ο ίδιος ανέλαβε σε σημαντικές αρχαιολογικές περιοχές της Ελλάδας, και τις συμφωνίες που έκανε ο ίδιος με τον Σουλτάνο προκειμένου τα αρχαιολογικά ευρήματα να εξαχθούν, προκειμένου να πουληθούν στις Ευρωπαίκές αγορές. Ο Brønsted απολαμβάνοντας της μεγάλης υποστήριξης του Αλή Πασά, μετατρέπεται σταδιακά σε «συνάδελφο» του Έλγιν που κατέκλεψε τις ελληνικές αρχαιότητες. Τον θησαυρό λόγου χάριν της Κέας τον φόρτωσε ο Δανός «αρχαιολάτρης» στο αγγλικό πλοίο «Η ωραία Νίνα» και πούλησε τα γλυπτά στη Δανία και τη δυτική Ευρώπη όπως αναγνωρίζει και ο ίδιος (P.O. Brønsted, Voyages dans la Grèce accompagnés de recherches archéologiques, Paris 1826-1830, σ. 24). Ο Brønsted, εκμεταλλευόμενος την υποστήριξη που είχε από τον Σουλτάνο, και, κυρίως, εκμεταλλευόμενος τον λαό της χώρας με την κλασική παιδεία, που ωστόσο σε εκείνη τη φάση ως πρωταρχικό μέλημά του έχει τον εθνικοαπελευθερωτικό του αγώνα, αδίκησε την Ελλάδα και λεηλάτησε τον πολιτισμό της. Ο ίδιος πρωταγωνίστησε στις ρυθμίσεις που αφορούσαν στην έξοδο ή την πώληση αυτών των ευρημάτων έξω από την Ελλάδα. Έτσι, μπορεί στη συνείδηση των Δανών να θεωρείται μια πνευματική προσωπικότητα, και μπορεί με τις παραδόσεις του στο Πανεπιστήμιο της Κοπεγχάγης να άσκησε μεγάλη επίδραση στους αστικούς ρομαντικούς κύκλους της πρωτεύουσας της Δανίας, αλλά, τελικά, η αντίληψη που επικράτησε γι’αυτόν τον καταδίκασε σε αρχαιοκάπηλο, και μάλιστα σε «αχρείο αρχαιοκάπηλο» 

INTRODUCTION: Geriatric depression is a heterogeneous disorder with a complex genetic background. Current first-line treatment of depression is associated with a lower therapeutic outcome in aged depressed patients, when compared to younger subjects. Research which has explored this inadequate response has highlighted several factors which have come into play with the pharmacogenetics of antidepressants in the elderly being a particular area of interest. AREAS COVERED: The authors perform a critical review of the English language articles from PubMed using search terms such as late-life/geriatric depression, antidepressants, pharmacogenetics, pharmacogenomics, pharmacokinetic, genetic, genotype, remission, therapy, treatment and polymorphism. EXPERT OPINION: The emerging clinical and pharmacogenetic data are slowly unveiling the importance of the genome - age interaction in antidepressant response. This data introduces a critical new parameter in personalized medicine. A profound analysis of the age factor in the pharmacogenetics of antidepressant response is imperative, in order to elucidate the clinical significance of these findings and thereby improve patient treatment in the elderly.

INTRODUCTION: Geriatric depression is a heterogeneous disorder with a complex genetic background. Current first-line treatment of depression is associated with a lower therapeutic outcome in aged depressed patients, when compared to younger subjects. Research which has explored this inadequate response has highlighted several factors which have come into play with the pharmacogenetics of antidepressants in the elderly being a particular area of interest. AREAS COVERED: The authors perform a critical review of the English language articles from PubMed using search terms such as late-life/geriatric depression, antidepressants, pharmacogenetics, pharmacogenomics, pharmacokinetic, genetic, genotype, remission, therapy, treatment and polymorphism. EXPERT OPINION: The emerging clinical and pharmacogenetic data are slowly unveiling the importance of the genome - age interaction in antidepressant response. This data introduces a critical new parameter in personalized medicine. A profound analysis of the age factor in the pharmacogenetics of antidepressant response is imperative, in order to elucidate the clinical significance of these findings and thereby improve patient treatment in the elderly.

INTRODUCTION: Geriatric depression is a heterogeneous disorder with a complex genetic background. Current first-line treatment of depression is associated with a lower therapeutic outcome in aged depressed patients, when compared to younger subjects. Research which has explored this inadequate response has highlighted several factors which have come into play with the pharmacogenetics of antidepressants in the elderly being a particular area of interest. AREAS COVERED: The authors perform a critical review of the English language articles from PubMed using search terms such as late-life/geriatric depression, antidepressants, pharmacogenetics, pharmacogenomics, pharmacokinetic, genetic, genotype, remission, therapy, treatment and polymorphism. EXPERT OPINION: The emerging clinical and pharmacogenetic data are slowly unveiling the importance of the genome - age interaction in antidepressant response. This data introduces a critical new parameter in personalized medicine. A profound analysis of the age factor in the pharmacogenetics of antidepressant response is imperative, in order to elucidate the clinical significance of these findings and thereby improve patient treatment in the elderly.

Molecular beam epitaxy has been employed to obtain Ga1−xMnxN films with x up to 10% and Curie temperatures TC up to 13 K. The magnitudes of TC and their dependence on x, TC(x)∝xm, where m=2.2±0.2, are quantitatively described by a tight-binding model of superexchange interactions and Monte Carlo simulations of TC. The critical behavior of this dilute magnetic insulator shows strong deviations from the magnetically clean case (x=1), in particular, (i) an apparent breakdown of the Harris criterion, (ii) a nonmonotonic crossover in the values of the susceptibility critical exponent γeff between the high temperature and critical regimes, and (iii) a smearing of the critical region, which can be explained either by the Griffiths effects or by macroscopic inhomogeneities in the spin distribution with a variance Δx=(0.2±0.1)%.

This phase II study is the first prospective evaluation of bortezomib-dexamethasone as second-line therapy for relapsed/refractory multiple myeloma. A total of 163 patients were enrolled to receive four cycles of bortezomibdexamethasone. Patients were investigator-assessed for response at cycle 5 Day 1, then treated as follows: responding patients received another four cycles of bortezomib-dexamethasone, while patients with stable disease were subsequently randomized to sequential treatment with a further four cycles of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide. The primary end point was response to sequential therapy; however, this could not be evaluated because investigator-assessed response rates to bortezomib-dexamethasone after four cycles were high, and an insufficient number of patients were randomized to sequential treatment per protocol. Among all 163 patients, validated best confirmed response rate was 66%, including 37% complete/very good partial responses; median response duration was 9.7 months. After a median follow up of 16.9 months, median time to progression and progression-free survival were 9.5 and 8.6 months, respectively; estimated 1-year overall survival was 81%. Median glomerular filtration rate improved from baseline during treatment. Among 58 patients with baseline glomerular filtration rate below 50 mL/min, 24 had renal responses. Grade 3/4 adverse events included: thrombocytopenia (17%), anemia (10%), constipation (6%), peripheral sensory neuropathy (5%), and polyneuropathy (5%). Overall, 57% of neuropathy events improved/resolved; median time to improvement was 2.1 months. These findings suggest bortezomib-dexamethasone represents an active, feasible second-line treatment option for patients with relapsed/refractory myeloma.. © 2013 Ferrata Storti Foundation.

Introduction: Phospholipases A2 have been implicated in various pathological conditions, such as rheumatoid arthritis, cardiovascular diseases, neurological disorders and cancer. The scientific community focuses on the search of potent and selective PLA2 inhibitors of each PLA2 class in order to identify novel medicinal agents. At present, only one lipoprotein-associated PLA2 (LpPLA2) inhibitor has reached Phase III clinical trials for the treatment of atherosclerosis. Areas covered: This review article focuses on the role of the most important PLA2s in inflammatory diseases and other severe pathological conditions presented in patent literature from June 2009 to September 2012. Expert opinion: Even though the role of each PLA2 in different diseases or pathological conditions is not yet definitively identified, the progress in the quest for potent and selective PLA2 inhibitors is exciting and the use of such inhibitors as medicinal agent looks now more promising than ever.

Microcystin-LR (MC-LR) is the most common and toxic variant of the group of microcystins (MCs) produced during the formation of harmful cyanobacterial blooms. Geosmin (GSM) and 2-methylisoborneol (MIB) may also be produced during cyanobacterial blooms and can taint water causing undesirable taste and odor. The photocatalytic degradation of MC-LR, GSM, and MIB in water under both UV-A and solar light in the presence of reduced graphene oxide-TiO2 composite (GO-TiO2) was studied. Two commercially available TiO 2 materials (Degussa P25 and Kronos) and a reference TiO2 material prepared in the laboratory (ref-TiO2) were used for comparison. Under UV-A irradiation, Degussa P25 was the most efficient photocatalyst for the degradation of all target analytes followed by GO-TiO 2, ref-TiO2, and Kronos. Under solar light irradiation GO-TiO2 presented similar photocatalytic activity to Degussa P25, followed by Kronos and ref-TiO2 which were less efficient. Intermediate products formed during the photocatalytic process with GO-TiO 2 under solar light were identified and were found to be almost identical to those observed by Degussa P25/UV-A. Assessment of the residual toxicity of MC-LR during the course of treatment with GO-TiO2 showed that toxicity is proportional only to the remaining MC-LR concentration. The photocatalytic performance of GO-TiO2 was also evaluated under solar light illumination in real surface water samples, and GO-TiO2 proved to be effective in the degradation of all target compounds. © 2013 American Chemical Society.

Visible light activated nanostructured TiO2 with nitrogen and fluorine co-dopants were prepared by the surfactant assisted sol-gel method and immobilized on glass substrates by dip coating. The films were inserted inside a continuous flow photoreactor and examined for the photocatalytic oxidation of NO air pollutant with initial concentration of 200-800ppbv. The modified catalysts exhibited significant photocatalytic activity under daylight illumination, with maximum percentage of NO removal equal to 24.2% and photooxidation rate up to 0.66μgm-2s-1. The reaction rates increased proportionally to the incident light intensity whereas for the strongly absorbed UV light a deviation from linearity was observed. Mass balance during photooxidation was confirmed by determining the amount of NO3- product residues onto the photocatalyst surface. © 2013 Elsevier B.V.

Introduite initialement par les photographes voyageurs et les photographes résidents, la photographie fut adoptée progressivement comme moyen de représentation par les artistes locaux de l’Orient méditerranéen. Formés en France ou associés aux photographes français, les photographes Orientaux devinrent progressivement autonomes, réussissant à rivaliser techniquement et artistiquement avec leurs collègues européens. De plus, présentés aux expositions internationales de Paris, les clichés des photographes comme Philippos Margaritis, Abdullah frères, Paul Sébah établit leur réputation en France. En outre, l’installation des photographes comme Bonfils au Proche-Orient contribua à la diffusion de l’art photographique dans la région

Aspergillus species originating from Greece were examined by morphological and molecular criteria to explore the diversity of this genus. The phylogenetic relationships of these species were determined using sequences from the ITS and IGS region of the nuclear rRNA gene complex, two nuclear genes ( β -tubulin (benA) and RNA polymerase II second largest subunit (rpb2)) and two mitochondrial genes (small rRNA subunit (rns) and cytochrome oxidase subunit I (cox1)) and, where available, related sequences from databases. The morphological characters of the anamorphs and teleomorphs, and the single gene phylogenetic trees, differentiated and placed the species examined in the well-supported sections of Aenei, Aspergillus, Bispori, Candidi, Circumdati, Clavati, Cremei, Flavi, Flavipedes, Fumigati, Nidulantes, Nigri, Restricti, Terrei, Usti, and Zonati, with few uncertainties. The combined use of the three commonly employed nuclear genes (benA, rpb2, and ITS), the IGS region, and two less often used mitochondrial gene sequences (rns and cox1) as a single unit resolved several taxonomic ambiguities. A phylogenetic tree was inferred using Neighbour-Joining, Maximum Parsimony, and Bayesian methods. The strains examined formed seven well-supported clades within the genus Aspergillus. Altogether, the concatenated nuclear and mitochondrial sequences offer additional tools for an improved understanding of phylogenetic relationships within this genus.

Objective To determine maternal serum concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) longitudinally in normal pregnancies, pregnancies that developed preeclampsia and pregnancies that deliver a small for gestational age (SGA) infant, in order to evaluate them as markers for the prediction of preeclampsia. Study design In this case-control study we included 12 singleton pregnancies that developed preeclampsia and 104 randomly selected singleton normal pregnancies. Fourteen of the normal pregnancies gave birth to an SGA infant. Blood samples and ultrasonographic data were collected during the 1st, 2nd and 3rd trimesters of pregnancy. Results In preeclamptic pregnancies, PlGF (pg/mL) (median; inter-quartile range) was significantly lower in the 2nd (208; 84-339) (p = 0.035) and in the 3rd trimester (202; 109-284) (p = 0.002) while sFlt-1 was significantly higher only in the 3rd trimester (2521; 2101-3041) (p = 0.011) compared to normal pregnancies (PlGF 2nd: 311; 243-440, PlGF 3rd: 780; 472-1037, sFlt-1 3rd: 1616; 1186-2220). In pregnancies with SGA infants, PlGF and sFlt-1 did not differ significantly from normal pregnancies in any trimester. The sFlt-1 to PlGF ratio was significantly higher in preeclamptic pregnancies than in normal pregnancies, in both the 2nd and 3rd trimesters. The relative difference and the slope of PlGF concentration between 1st and 2nd trimester were significantly reduced in preeclampsia compared to normal pregnancies. A logistic regression model with predictors BMI, 2nd trimester Doppler PI and relative difference of PlGF from the 1st to the 2nd trimester gave 46% sensitivity and 99% specificity for the prediction of preeclampsia, with a very high negative predictive value of 98.3%. Conclusions Our study confirms that maternal serum PlGF concentration is significantly lower, at least after 20th week, while sFlt-1 concentration is significantly higher in 3rd trimester, in pregnancies destined to develop preeclampsia. Pregnancies that gave birth to SGA infants do not have altered angiogenic factor concentrations throughout pregnancy. The relative difference of PlGF from the 1st to the 2nd trimester, uterine artery Doppler PI in the 2nd trimester and BMI are the most powerful markers for the prediction of preeclampsia. © 2013 Elsevier Ireland Ltd © 2013 Published by Elsevier Ireland Ltd. All rights reserved.

Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathological entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (≥20%) and absolute number (≥2 × 10 9/l) of plasma cells in the peripheral blood. It is proposed that the thresholds for diagnosis be re-examined and consensus recommendations are made for diagnosis, as well as, response and progression criteria. Induction therapy needs to begin promptly and have high clinical activity leading to rapid disease control in an effort to minimize the risk of early death. Intensive chemotherapy regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem cell transplantation if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding of the pathogenesis of PCL. © 2013 Macmillan Publishers Limited All rights reserved.

Multiple myeloma remains an incurable disease despite the introduction of the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome inhibitor bortezomib that have improved the outcome of patients with both newly diagnosed and relapsed/ refractory disease. However, patients who relapse after treatment with these agents or are refractory to them represent an unmet need and highlight the necessity for the development of novel anti-myeloma agents. Pomalidomide is an IMiD, structurally related to thalidomide, with enhanced antiangiogenic, antineoplastic, and anti-inflammatory properties and exhibiting potent anti-myeloma activity in vitro and in vivo. Pomalidomide has shown remarkable activity in patients who were refractory to both bortezomib and lenalidomide in Phase II and III studies. This paper reviews the chemistry and mechanisms of action of pomalidomide as well as all the available data from clinical trials on pomalidomide use in patients with refractory/relapsed multiple myeloma. © 2013 Terpos et al, publisher and licensee Dove Medical Press Ltd.

Background: Few effective treatments exist for patients with refractory or relapsed and refractory multiple myeloma not responding to treatment with bortezomib and lenalidomide. Pomalidomide alone has shown limited efficacy in patients with relapsed multiple myeloma, but synergistic effects have been noted when combined with dexamethasone. We compared the efficacy and safety of pomalidomide plus low-dose dexamethasone with high-dose dexamethasone alone in these patients. Methods: This multicentre, open-label, randomised phase 3 trial was undertaken in Australia, Canada, Europe, Russia, and the USA. Patients were eligible if they had been diagnosed with refractory or relapsed and refractory multiple myeloma, and had failed at least two previous treatments of bortezomib and lenalidomide. They were assigned in a 2:1 ratio with a validated interactive voice and internet response system to either 28 day cycles of pomalidomide (4 mg/day on days 1-21, orally) plus low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally) or high-dose dexamethasone (40 mg/day on days 1-4, 9-12, and 17-20, orally) until disease progression or unacceptable toxicity. Stratification factors were age (≤75 years vs >75 years), disease population (refractory vs relapsed and refractory vs bortezomib intolerant), and number of previous treatments (two vs more than two). The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01311687, and with EudraCT, number 2010-019820-30. Findings: The accrual for the study has been completed and the analyses are presented. 302 patients were randomly assigned to receive pomalidomide plus low-dose dexamethasone and 153 high-dose dexamethasone. After a median follow-up of 10·0 months (IQR 7·2-13·2), median PFS with pomalidomide plus low-dose dexamethasone was 4·0 months (95% CI 3·6-4·7) versus 1·9 months (1·9-2·2) with high-dose dexamethasone (hazard ratio 0·48 [95% CI 0·39-0·60]; p<0·0001). The most common grade 3-4 haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups were neutropenia (143 [48%] of 300 vs 24 [16%] of 150, respectively), anaemia (99 [33%] vs 55 [37%], respectively), and thrombocytopenia (67 [22%] vs 39 [26%], respectively). Grade 3-4 non-haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups included pneumonia (38 [13%] vs 12 [8%], respectively), bone pain (21 [7%] vs seven [5%], respectively), and fatigue (16 [5%] vs nine [6%], respectively). There were 11 (4%) treatment-related adverse events leading to death in the pomalidomide plus low-dose dexamethasone group and seven (5%) in the high-dose dexamethasone group. Interpretation: Pomalidomide plus low-dose dexamethasone, an oral regimen, could be considered a new treatment option in patients with refractory or relapsed and refractory multiple myeloma. Funding: Celgene Corporation. © 2013 Elsevier Ltd.

Poor oral health, including caries, tooth loss, and periodontitis, is ubiquitous worldwide, and is potentially treatable and preventable. Like adverse oral health conditions, Alzheimer disease and related disorders are also very common among aging populations. Established risk factors for Alzheimer disease include cerebrovascular disease and its vascular risk factors, many of which share associations with evidence of systemic inflammation also identified in periodontitis and other poor oral health states. In this review, we present epidemiologic evidence of links between poor oral health and both prevalent and incident cognitive impairment, and review plausible mechanisms linking these conditions, including evidence from compelling animal models. Considering that a large etiologic fraction of dementia remains unexplained, these studies argue for further multidisciplinary research between oral health conditions, including translational, epidemiologic, and possibly clinical treatment studies.

A novel potentiometric cholesterol biosensor has been fabricated through the immobilization of the stabilized polymeric lipid membrane onto graphene electrode. The stabilized polymeric lipid membrane is composed of cholesterol oxidase enzyme and polymerization mixture; which holds paramount influence on the properties of the cholesterol biosensor. The presented biosensor reveals an appreciable reproducibility, good selectivity and high sensing capability with a linear slope curve of ∼64 mV per decade. The strong biocompatibility among stabilized polymeric lipid membranes and human biofluids provides the possibility to use for real blood samples and other biological applications. © 2013 Versita Warsaw and Springer-Verlag Wien.

Histone deacetylases (HDACs) mediate protein acetylation states, which in turn regulate normal cellular processes often dysregulated in cancer. These observations led to the development of HDAC inhibitors that target tumors through multiple effects on protein acetylation. Clinical evidence demonstrates that treatment with HDAC inhibitors (such as vorinostat, panobinostat, and romidepsin) in combination with other antimyeloma agents (such as proteasome inhibitors and immunomodulatory drugs) has promising antitumor activity in relapsed/refractory multiple myeloma patients. This mini-review highlights the role of protein acetylation in the development of cancers and the rationale for the use of HDAC inhibitors in this patient population. © 2013 Elsevier Ltd.

The paleoenviromental conditions during the depositional interval of sapropel S1 in the northeastern Aegean (gravity core M-4, length 2.53 m; south Limnos basin) are studied based on quantitative micropaleontological (benthic and planktonic foraminifera) and geochemical (OC, δ13Corg) analyses. Special feature of core M-4 is the thickness of S1 layer (96 cm). Our study points that sapropelic layer S1a has been deposited in more dysoxic and warmer conditions in respect to S1b. Both primary productivity and preservation of organic material are more intense during the lower part of S1. An interruption of the sapropelic conditions at 8.0 Ka BP which is mainly characterized by the increase of agglutinated foraminiferal forms confirms both higher oxygen bottom conditions and freshwater input.

We aimed to investigate the effect of metal ions on the semen of males of child fathering age with metal-on-metal (MM) total hip arthroplasty (THA). Semen was collected form 11 patients with MM THA and 5 control of comparable age. Cobalt and chromium concentrations were measured in both the seminal plasma and in the blood of patients. Results showed that cobalt level was higher in the seminal plasma of MM THA patients (2.89 μg/L) compared to control patients (1.12 μg/L) (P = .011). The ejaculate volume, the sperm density, the total sperm count, the pH, and the percentage of cells with normal morphology were in the range of the World Health Organization criteria for fertile population.

From the 2008-2009 European Bacteroides antibiotic resistance survey, we selected 161 strains for detection of antibiotic resistance genes (cepA, cfxA, cfiA, nim, ermB, ermF, ermG, linA, mefA, msrSA, tetM, tetQ, tetX, tetX1, tet36 and bexA). To facilitate the throughput, the genes were detected by Real-Time PCR. The presence of the genes was correlated with the known MIC data of the strains for the appropriate antibiotics. For the β-lactams, the cepA gene was found in 70.8% of the tested strains (all resistant to ampicillin), but its presence did not correlate with the ampicillin MIC values. The cepA gene occurred at different frequencies among Bacteroides fragilis and non-fragilis Bacteroides strains. The cfxA gene was not a major factor in determining cefoxitin resistance and it was found with higher prevalence in non-fragilis Bacteroides strains than in B. fragilis. Among the five possible clindamycin resistance genes, ermF was the most common and had the highest effect on clindamycin resistance after linA. The ermG-mefA-msrSA combination was found in a set of strains and their linked occurrence implied that they were harbored by the conjugative transposon CTnGERM1. All strains tested were susceptible to metronidazole and none of them harbored nim genes. TetQ was prevalent among both the B. fragilis and non-fragilis Bacteroides strains (78.9 and 84.8%, respectively) and no gene could be clearly linked to tigecycline resistance other than tetQ. BexA, which codes for the fluoroquinolone efflux pump, was found in 7.5% of strains and occurred at different frequencies among B. fragilis and non-fragilis Bacteroides strains, but was represented only in a minor proportion of moxifloxacin-resistant strains.

Germline mutations in the BRCA1 and BRCA2 genes contribute to approximately 18% of hereditary ovarian cancers conferring an estimated lifetime risk from 15% to 50%. A variable incidence of mutations has been reported for these genes in ovarian cancer cases from different populations. In Greece, six mutations in BRCA1 account for 63% of all mutations detected in both BRCA1 and BRCA2 genes. This study aimed to determine the prevalence of BRCA1 mutations in a Greek cohort of 106 familial ovarian cancer patients that had strong family history or metachronous breast cancer and 592 sporadic ovarian cancer cases. All 698 patients were screened for the six recurrent Greek mutations (including founder mutations c.5266dupC, p.G1738R and the three large deletions of exon 20, exons 23-24 and exon 24). In familial cases, the BRCA1 gene was consequently screened for exons 5, 11, 12, 20, 21, 22, 23, 24. A deleterious BRCA1 mutation was found in 43/106 (40.6%) of familial cancer cases and in 27/592 (4.6%) of sporadic cases. The variant of unknown clinical significance p.V1833M was identified in 9/698 patients (1.3%). The majority of BRCA1 carriers (71.2%) presented a high-grade serous phenotype. Identifying a mutation in the BRCA1 gene among breast and/or ovarian cancer families is important, as it enables carriers to take preventive measures. All ovarian cancer patients with a serous phenotype should be considered for genetic testing. Further studies are warranted to determine the prevalence of mutations in the rest of the BRCA1 gene, in the BRCA2 gene, and other novel predisposing genes for breast and ovarian cancer. © 2013 Stavropoulou et al.

AIM: To determine the prevalence and frequency of non classical congenital adrenal hyperplasia (NC-CAH) due to 21-OHD at the time of clinical presentation and at the peripubertal period in a substantial sample of Greek women with acne and to investigate the correlation of serum T, 17-OHP and DHEA-S with acne appearance at the time of clinical presentation. METHODS: One hundred and twenty-three unselected women with hyperandrogenemic symptoms were examined. After the ACTH stimulation test, 6 (4.9%) women were diagnosed with NC-CAH due to 21-OHD. RESULTS: There was not any statistical significant difference in the frequency of peripubertal acne between NC-CAH group of patients (6.4%) and patients with hyperandrogenemia of other aetiology (93%), mainly ovarian (P = 0.41). However, there was a statistical significant difference in the prevalence of acne at the time of clinical examination between the two groups (P = 0.04). Acne was present in 83.3% of women with NC-CAH vs. 41.02% of women in the hyperandrogenic group without NC-CAH. A statistically significant decrease of acne from the peripubertal time to the time of clinical examination in the group of women with hyperandrogenemia of other aetiology (-21.37%) was observed compared to women with NC-CAH (P < 0.001). CONCLUSION: We have shown that acne persists from peripubertal period to adult life in NC-CAH women whereas it tends to diminish in women with hyperandrogenemia of other aetiology. Acne is a prominent finding in women with NC-CAH. Serum concentrations of 17-OHP after ACTH stimulation (17-OHP6O ) should be investigated in women with persistent acne in adult life.

Aim: To assess the prevalence of climacteric symptoms and their association with demographic, life-style and hormonal parameters in Greek peri-and recently postmenopausal women. Methods: 1025 Greek women who were either perimenopausal or within their first 5 postmenopausal years participated in this cross-sectional observational study. Menopausal symptoms were assessed by the Greene Climacteric Scale and were tested for associations with demographic, anthropometric, life-style and hormonal parameters. Results: 29.8% Of the women reported moderate to severe menopausal symptoms. More specifically, 39.2% reported vasomotor, 21.3% psychological, 6.3% psychosomatic and 34.5% sexual symptoms. Years since menopause (r = 0.13, p < 0.01), waist circumference (r = 0.11, p < 0.05) as well as serum FSH, LH and estradiol (r = 0.15, r = 0.118, r =-0.157; p < 0.01) correlated with the intensity of menopausal symptoms. In the multivariate analysis years since menopause and serum estradiol were the only significant predictors of menopausal symptoms (b =-0.158 and b =-0.198, p < 0.001, respectively), explaining though only 4.8% of the variance. Conclusion: One out of three Greek women has moderate to severe climacteric symptoms during the menopause transition or the first postmenopausal years. This frequency is comparable to other White populations. Menopausal age and endogenous estrogens are significant predictors of climacteric symptoms. © 2013 Informa UK, Ltd.

In this phase 2 multicenter trial, we evaluated the activity of bortezomib, dexamethasone, and rituximab (BDR) combination in previously untreated symptomatic patients with Waldenström macroglobulinemia (WM). To prevent immunoglobulin M (IgM) "flare," single agent bortezomib (1.3 mg/m 2 IV days 1, 4, 8, and 11;21-day cycle), was followed by weekly IV bortezomib (1.6 mg/m2 days 1, 8, 15, and 22) every 35 days for 4 additional cycles, followed by IV dexamethasone (40 mg) and IV rituximab (375 mg/m2) in cycles 2 and 5. Fifty-nine patients were treated; 45.5% and 40% were high and intermediate risk per the International Prognostic Scoring System for WM. On intent to treat, 85% responded (3% complete response, 7% very good partial response, 58% partial response [PR]).In 11% of patients, an increase of IgM ≥25% was observed after rituximab; no patient required plasmapheresis. After a minimum follow-up of 32 months, median progression-free survival was42months, 3-year durationof response for patients with≥PR was 70%, and 3-year survival was 81%. Peripheral neuropathy occurred in 46% (grade ≥3 in 7%); only 8% discontinued bortezomib due to neuropathy. BDR is rapidly acting, well tolerated, and nonmyelotoxic, inducing durable responses in previously untreated WM. © 2013 by The American Society of Hematology.

Background:Discrepant data have been published on the incidence and prognostic significance of ESR1 gene amplification in early breast cancer.Patients and Methods:Formalin-fixed paraffin-embedded tumor blocks were collected from women with early breast cancer participating in two HeCOG adjuvant trials. Messenger RNA was studied by quantitative PCR, ER protein expression was centrally assessed using immunohistochemistry (IHC) and ESR1 gene copy number by dual fluorescent in situ hybridization probes.Results:In a total of 1010 women with resected node-positive early breast adenocarcinoma, the tumoral ESR1/CEP6 gene ratio was suggestive of deletion in 159 (15.7%), gene gain in 551 (54.6%) and amplification in 42 cases (4.2%), with only 30 tumors (3%) harboring five or more ESR1 copies. Gene copy number ratio showed a significant, though weak correlation to mRNA and protein expression (Spearman's Rho <0.23, p = 0.01). ESR1 clusters were observed in 9.5% (57 gain, 38 amplification) of cases. In contrast to mRNA and protein expression, which were favorable prognosticators, gene copy number changes did not obtain prognostic significance. When ESR1/CEP6 gene ratio was combined with function (as defined by ER protein and mRNA expression) in a molecular classifier, the Gene Functional profile, it was functional status that impacted on prognosis. In univariate analysis, patients with functional tumors (positive ER protein expression and gene ratio normal or gain/amplification) fared better than those with non-functional tumors with ESR1 gain (HR for relapse or death 0.49-0.64, p = 0.003). Significant interactions were observed between gene gain/amplification and paclitaxel therapy (trend for DFS benefit from paclitaxel only in patients with ESR1 gain/amplification, p = 0.066) and Gene Functional profile with HER2 amplification (Gene Functional profile prognostic only in HER2-normal cases, p = 0.029).Conclusions:ESR1 gene deletion and amplification do not constitute per se prognostic markers, instead they can be classified to distinct prognostic groups according to their protein-mediated functional status. © 2013 Pentheroudakis et al.

Natural hazards pose an increasing threat to society and, for this reason, it is necessary to develop models and methodologies for better understanding and forecasting extreme weather events. A new structure of the Greek Regional Administration (Kallikratis) was established in 2011, based on geographical criteria, in order to create an operational and capable administration. An Atmospheric Hazards Early Warning System (AHEWS) could be characterised as an ultimate tool for the local authorities (first and second tier level) in order to organise and implement efficient plans to mitigate the risk. New operation centres (related to regional and municipality administration level) are suggested to be staffed and equipped with the proposed Early Warning System (EWS). The AHEWS will link to extensive Geographical Information Systems (GIS) datasets and methodologies for safety plans by government agencies and services in order to mitigate the impacts caused by atmospheric extreme events. AHEWS involves high-resolution Numerical Weather Prediction (NWP) products, ground observation network, lightning detection network and satellite information in terms of early convective, initiation and Now-Casting. Storms, lightings, gale winds, snow, hail, tornadoes, low temperatures, heatwaves and several others extreme events are weather phenomena that AHEWS deals with in order to prevent and mitigate impacts on humans and constructions. An automated dissemination procedure is described here for individual and administrative users, followed by safety and action plans, respectively. © 2013 Taylor & Francis.

Multiple myeloma (MM) typically follows a relapsing course with many patients requiring multiple therapies. This single-arm phase 2 study prospectively evaluated the efficacy and safety of bortezomib retreatment in MM patients who had relapsed after achieving at least a partial response (≥PR) to prior bortezomib-based therapy. Patients aged ≥18years, with measurable, secretory MM, who relapsed ≥6months after prior bortezomib treatment were eligible. Patients received up to eight cycles of bortezomib (±dexamethasone). The primary endpoint was best confirmed response at retreatment; secondary endpoints included duration of response (DOR), time to progression (TTP), and safety. Adverse events (AEs) were graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. A total of 130 patients (median of two prior lines of therapy) were enrolled and received retreatment. At retreatment, 28% and 72% of patients received bortezomib and bortezomib-dexamethasone, respectively. Overall response rate was 40%. In patients who achieved ≥PR, median DOR and TTP were 6·5 and 8·4months, respectively. Thrombocytopenia was the most common grade ≥3 AE (35%). Forty percent of patients experienced neuropathy events, which improved and resolved in a median of 1·5 and 8·9months, respectively. In conclusion, bortezomib retreatment was effective and tolerable in relapsed MM patients, with no evidence of cumulative toxicities. © 2013 Blackwell Publishing Ltd.

Background: The combinations of methotrexate, vinblastine, Adriamycin, cisplatin (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the standard treatment of advanced urothelial cancer (UC). Dosedense (DD)-MVAC has achieved longer progression-free survival (PFS) than the conventional MVAC. However, the role of GC intensification has not been studied. We conducted a randomized, phase III study comparing a DD-GC regimen with DD-MVAC in advanced UC. Patients and methods: One hundred and thirty patients were randomly assigned between DD-MVAC: 66 (M 30 mg/ m2, V 3 mg/m2, A 30 mg/m2, C 70 mg/m2 q 2 weeks) and DD-GC 64 (G 2500 mg/m2, C 70 mg/m2 q 2 weeks). The median follow-up was 52.1 months (89 events). Results: The median overall survival (OS) and PFS were 19 and 8.5 months for DD-MVAC and 18 and 7.8 months for DD-GC (P = 0.98 and 0.36, respectively). Neutropenic infections were less frequent for DD-GC than for DD-MVAC (0% versus 8%). More patients on DD-GC received at least six cycles of treatment (85% versus 63%, P = 0.011) and the discontinuation rate was lower for DD-GC (3% versus 13%). Conclusions: Although DD-GC was not superior to DD-MVAC, it was better tolerated. DD-GC could be considered as a reasonable therapeutic option for further study in this patient population. Clinical Trial Number: ACTRN12610000845033, www.anzctr.org.au. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

The ubiquitin-proteasome system is central to the regulation of cellular proteostasis. Nevertheless, the impact of in vivo proteasome dysfunction on the proteostasis networks and the aging processes remains poorly understood. We found that RNAi-mediated knockdown of 20S proteasome subunits in Drosophila melanogaster resulted in larval lethality. We therefore studied the molecular effects of proteasome dysfunction in adult flies by developing a model of dose-dependent pharmacological proteasome inhibition. Impaired proteasome function promoted several 'old-age' phenotypes and markedly reduced flies' lifespan. In young somatic tissues and in gonads of all ages, loss of proteasome activity induced higher expression levels and assembly rates of proteasome subunits. Proteasome dysfunction was signaled to the proteostasis network by reactive oxygen species that originated from malfunctioning mitochondria and triggered an Nrf2-dependent upregulation of the proteasome subunits. RNAi-mediated Nrf2 knockdown reduced proteasome activities, flies' resistance to stress, as well as longevity. Conversely, inducible activation of Nrf2 in transgenic flies upregulated basal proteasome expression and activity independently of age and conferred resistance to proteotoxic stress. Interestingly, prolonged Nrf2 overexpression reduced longevity, indicating that excessive activation of the proteostasis pathways can be detrimental. Our in vivo studies add new knowledge on the proteotoxic stress-related regulation of the proteostasis networks in higher metazoans. Proteasome dysfunction triggers the activation of an Nrf2-dependent tissue- and age-specific regulatory circuit aiming to adjust the cellular proteasome activity according to temporal and/or spatial proteolytic demands. Prolonged deregulation of this proteostasis circuit accelerates aging. © 2013 The Anatomical Society and John Wiley & Sons Ltd.

Proteasome inhibitors effectively kill tumor cells in myeloma and other plasma cell-related diseases. Preclinical data indicated that lymphoplasmatic cells are also vulnerable to proteasome inhibition and proteasome-targeting therapies have proved their clinical activity in Waldenström's macroglobulinemia (WM). Bortezomib is the first in class proteasome inhibitor (PI), and has been used in several clinical trials either alone or in combination with rituximab. Bortezomib treatment alone might induce major responses in 25%-60% of patients with WM but in combination with rituximab major responses might be as high as 50%-83%. Bortezomib might reduce immunoglobulin M levels rapidly and is not myelotoxic. However, peripheral neuropathy remains a major toxicity of bortezomib therapy; alternative schedules and dosing or route of administration (subcutaneous) might reduce neurotoxicity. Second generation PIs, such as carfilzomib, are also promising but further investigation is needed. © 2013 Elsevier Inc.

Background: Active cancer immunotherapies are beginning to yield clinical benefit, especially those using peptide-pulsed dendritic cells (DCs). Different adjuvants, including Toll-like receptor (TLR) agonists, commonly co-administered to cancer patients as part of a DC-based vaccine, are being widely tested in the clinical setting. However, endogenous DCs in tumor-bearing individuals are often dysfunctional, suggesting that ex vivo educated DCs might be superior inducers of anti-tumor immune responses. We have previously shown that prothymosin alpha (proTα) and its immunoreactive decapeptide proTα(100-109) induce the maturation of human DCs in vitro. The aim of this study was to investigate whether proTα- or proTα(100-109)-matured DCs are functionally competent and to provide preliminary evidence for the mode of action of these agents.Results: Monocyte-derived DCs matured in vitro with proTα or proTα(100-109) express co-stimulatory molecules and secrete pro-inflammatory cytokines. ProTα- and proTα(100-109)-matured DCs pulsed with HER-2/neu peptides induce TH1-type immune responses, prime autologous naïve CD8-positive (+) T cells to lyse targets expressing the HER-2/neu epitopes and to express a polyfunctional profile, and stimulate CD4+ T cell proliferation in an HER-2/neu peptide-dependent manner. DC maturation induced by proTα and proTα(100-109) is likely mediated via TLR-4, as shown by assessing TLR-4 surface expression and the levels of the intracellular adaptor molecules TIRAP, MyD88 and TRIF.Conclusions: Our results suggest that proTα and proTα(100-109) induce both the maturation and the T cell stimulatory capacity of DCs. Although further studies are needed, evidence for a possible proTα and proTα(100-109) interaction with TLR-4 is provided. The initial hypothesis that proTα and the proTα-derived immunoactive decapeptide act as " alarmins" , provides a rationale for their eventual use as adjuvants in DC-based anti-cancer immunotherapy. © 2013 Ioannou et al.; licensee BioMed Central Ltd.

A coastal management study at areas with steep anaglyph requires detailed knowledge of the onshore surface and subsurface regime regarding the erosional procedures. Active faults produce dynamic and continuously evolving geomorphological structures, which require investigation and continuous monitoring. Detailed mapping on and adjacent to these surfaces is required in order to study the complexity of various tectonic discontinuities, which contribute significantly to erosion and rock-falls resulting rapid and significant changes on the landscape. The technology of ground-based Light Detection and Range (LiDAR) capturing devices is a powerful and valuable tool, providing detailed mapping and surface change detection of inapproachable and nearly vertical surfaces. In this paper we introduce the diachronic monitoring and detection of alterations on the surface of the shore-side active fault of Psatha (Greece), with terrestrial LiDAR scanning, for a state of the art mapping of the almost vertical limestone fault surface. The monitoring procedure includes high-detailed topographic survey at the adjacent area using Real Time Kinematics Global Positioning System equipment (RTK-GPS), which is consisted of a large pile of brittle debris, laying on top the fault surface, by the sea. The described methodology involved the production of a high resolution DEM based on historic topographic maps (scale 1:5,000) of the regional area and comparing it with the higher resolution DEM representing the contemporary morphology, produced by the combination of the fault wall LiDaR “point cloud” and the dense grid of the RTK-GPS measurement points. The comparison between these datasets and recently acquired high resolution IKONOS satellite images revealed impressive surface changes caused mainly by the human intervention as well as the erosional processes which were accelerated due to the absence of safety measures along the coastal zone. Furthermore, the regional subsurface of the hanging wall zone area was also investigated, especially underneath the brittle debris formation, applying the highresolution near surface geophysical technique of Electrical Resistivity Tomography (ERT). Several sections were conducted aiming to represent the subsurface extension of the visible structures in three dimensions and combine it with the aforementioned datasets. The successful combination of different techniques revealed and quantified the landscape evolution involving the surface alternations at the fault adjacent coastal zone, the sea intrusion and even the coastline displacement, during the last four decades. Most of these yielded to the anthropogenic interference on the brittle debris formation and even the construction of the coastal road.

Generics are usually considered to exhibit comparable in vivo properties in terms of efficacy and safety and for this reason are intended to be interchangeable with the reference product. The aim of this study is to provide a quantitative picture of the switchability problem between two generics and to introduce the concept of conditional probability of bioequivalence (BE) acceptance. Monte Carlo simulations were performed to examine all possible relationships between the tested products. Four types of percent BE acceptances are defined and evaluated: (a) % BA1, when generic T-1 is compared to the R product, (b) % BA2, in cases of comparison of generic T-2 with the R product, (c) % BA21, when generic T-2 is compared to another generic T-1, and finally (d) % BA21C which is the conditional probability of percent bioequivalence acceptance of generic T(2)versus another generic T-1 given that both T-1 and T-2 are declared bioequivalent to the same R formulation. The simulations were expanded to study concomitantly the performance of T-1 and T-2 when compared to the same R formulation. In each case, the 2 x 2 cross-over design was used and evaluation of BE was based on the classic BE limits (0.80-1.25) and the stricter BE limits (0.90-1.11) for narrow therapeutic index (NTI) drugs. A number of 24 and 48 subjects were assumed to participate in the simulated trials, while the coefficient of variation for the within-subject variability (CVw) was 20% and 40%. A number 40,000 BE trials were simulated under each condition. The T-1/R and T-2/R ratios ranged from 0.80 to 1.25 using a step of 0.05. Even though two generics (T-1 and T-2) can be declared bioequivalent to the same R product, this does not ensure that they are always mutually bioequivalent. On the contrary, two generic products which differ substantially from the R product can still have a high probability to be truly interchangeable. The two generics (T-1 and T-2) can be switched from one to another when the T-1/R and T-2/R ratios are close to the same value, the CVw of the drug is low, and each BE study of T-1-R and T-2-R was conducted using a relatively large number of subjects. In the same context, two generic NTI drugs which differ more than 10% from the R product can still be declared bioequivalent to one another depending on the relative T-1/R and T-2/R ratios. Switchability between generics assessed at the 0.90-1.11 interval is safer, but not always ensured. (C) 2013 Elsevier B.V. All rights reserved.

The forecast of extreme weather events become imperative due to the emerging climate change and possible adverse effects in humans. The objective of this study is to construct predictive models in order to forecast rain intensity (mm/day) in Athens, Greece, using Artificial Neural Networks (ANN) models. The ANNs outcomes concern the projected mean, maximum and minimum monthly rain intensity for the next four consecutive months in Athens. The meteorological data used to estimate the rain intensity, were the monthly rain totals (mm) and the respective rain days, which were acquired from the National Observatory of Athens, for a 111-year period (1899-2009). The results of the developed and applied ANN models showed a fairly reliable forecast of the rain intensity for the next four months. For the evaluation of the results and the ability of the developed prognostic models, appropriate statistical indices were taken into consideration. In general, the predicted rain intensity compared with the corresponding observed one seemed to be in a very good agreement at a statistical significance level of p. <. 0.01. © 2011 Elsevier B.V.

Relativistic jets associated with long/soft gamma-ray bursts are formed and initially propagate in the interior of the progenitor star. Because of the subsequent loss of their external pressure support after they cross the stellar surface, these flows can be modelled as moving around a corner. A strong steady-state rarefaction wave is formed, and the sideways expansion is accompanied by a rarefaction acceleration. We investigate the efficiency and the general characteristics of this mechanism by integrating the steady-state, special relativistic, magnetohydrodynamic equations, using a special set of partial exact solutions in planar geometry (r self-similar with respect to the `corner'). We also derive analytical approximate scalings in the ultrarelativistic cold/magnetized, and hydrodynamic limits. The mechanism is more effective in magnetized than in purely hydrodynamic flows. It substantially increases the Lorentz factor without much affecting the opening of the jet; the resulting values of their product can be much greater than unity, allowing for possible breaks in the afterglow light curves. These findings are similar to the ones from numerical simulations of axisymmetric jets by Komissarov et al. and Tchekhovskoy et al., although in our approach we describe the rarefaction as a steady-state simple wave and self-consistently calculate the opening of the jet that corresponds to zero external pressure.

Relativistic jets associated with long/soft gamma-ray bursts are formed and initially propagate in the interior of the progenitor star. Because of the subsequent loss of their external pressure support after they cross the stellar surface, these flows can be modelled as moving around a corner. A strong steady-state rarefaction wave is formed, and the sideways expansion is accompanied by a rarefaction acceleration. We investigate the efficiency and the general characteristics of this mechanism by integrating the steady-state, special relativistic, magnetohydrodynamic equations, using a special set of partial exact solutions in planar geometry (r self-similar with respect to the `corner'). We also derive analytical approximate scalings in the ultrarelativistic cold/magnetized, and hydrodynamic limits. The mechanism is more effective in magnetized than in purely hydrodynamic flows. It substantially increases the Lorentz factor without much affecting the opening of the jet; the resulting values of their product can be much greater than unity, allowing for possible breaks in the afterglow light curves. These findings are similar to the ones from numerical simulations of axisymmetric jets by Komissarov et al. and Tchekhovskoy et al., although in our approach we describe the rarefaction as a steady-state simple wave and self-consistently calculate the opening of the jet that corresponds to zero external pressure.

Realism: Annotated BibliographyOxford University Press

International Staging System (ISS), serum free light chain ratio (sFLCR) and lactate dehydrogenase (LDH) are well known, easily assessed independent prognostic indicators of outcome in multiple myeloma (MM). The purpose of the study was to re-examine the prognostic contribution of these variables in a multicenter setting with special attention to MM patients treated with autologous stem cell transplantation (ASCT) or novel agents (NA). Three hundred and five symptomatic newly diagnosed MM patients were retrospectively studied. Twenty-seven per cent, 32% and 41% were in ISS stages 1, 2, and 3, respectively. Fifty-six per cent of them presented kappa light chain monoclonality; median sFLCR was 27.04 (0.37-1.9×105) and 47.97 (0.26-2.3×107) for kappa patients and lambda patients, respectively; patients with sFLCR above median constituted the high sFLCR group. Thirty-one per cent of patients had increased LDH. As first line treatment, 55.7% received conventional treatment and 44.3% NA. After induction, 24% underwent ASCT, whereas 76% received NA at any line, either bortezomib (82.5%), thalidomide (48%) or lenalidomide (27%). When the 305 patients were analyzed together, staging, high sFLCR and abnormal LDH were predictive of survival. The same was true for patients that never received NA, whereas neither high sFLCR nor abnormal LDH constituted adverse factors in patients that received NA frontline. In the last group of patients, no difference was observed between ISS stages 2 and 3. The median 5-year survival of patients that never received NA versus those who did frontline was 29% vs 47%, 7% vs 52% and 24% vs 40% in patients with abnormal LDH, high sFLCR and ISS stage 3, respectively (p=0.03, p<0.00001 and p=0.035). In conclusion, patients gaining the most from NA are those with an aggressive disease as reflected by advanced stage, abnormal LDH and high sFLCR. In addition, the adverse impact of these three variables is obscured by NA. © 2012 John Wiley & Sons, Ltd.

IMPORTANCE: Adherence to Mediterranean-type diet (MeDi) may delay onset of Alzheimer and Parkinson diseases. Whether adherence to MeDi affects time to phenoconversion in Huntington disease (HD), a highly penetrant, single-gene disorder, is unknown. OBJECTIVES: To determine if MeDi modifies the time to clinical onset of HD (phenoconversion) in premanifest carriers participating in Prospective Huntington at Risk Observational Study (PHAROS), and to examine the effects of body mass index and caloric intake on time to phenoconversion. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of 41 Huntington study group sites in the United States and Canada involving 1001 participants enrolled in PHAROS between July 1999 and January 2004 who were followed up every 9 months until 2010. A total of 211 participants aged 26 to 57 years had an expanded CAG repeat length (≥ 37). EXPOSURE: A semiquantitative food frequency questionnaire was administered 33 months after baseline. We calculated daily gram intake for dairy, meat, fruit, vegetables, legumes, cereals, fish, monounsaturated and saturated fatty acids, and alcohol and constructed MeDi scores (0-9); higher scores indicate higher adherence. Demographics, medical history, body mass index, and Unified Huntington's Disease Rating Scale (UHDRS) score were collected. MAIN OUTCOME AND MEASURE: Cox proportional hazards regression models to determine the association of MeDi and phenoconversion. RESULTS Age, sex, caloric intake, education status, and UHDRS motor scores did not differ among MeDi tertiles (0-3, 4-5, and 6-9). The highest body mass index was associated with the lowest adherence to MeDi. Thirty-one participants phenoconverted. In a model adjusted for age, CAG repeat length, and caloric intake, MeDi was not associated with phenoconversion (P for trend = 0.14 for tertile of MeDi, and P = .22 for continuous MeDi). When individual components of MeDi were analyzed, higher dairy consumption (hazard ratio, 2.36; 95% CI, 1.0-5.57; P = .05) and higher caloric intake (P = .04) were associated with risk of phenoconversion. CONCLUSIONS AND RELEVANCE: MeDi was not associated with phenoconversion; however, higher consumption of dairy products had a 2-fold increased risk and may be a surrogate for lower urate levels (associated with faster progression in manifest HD). Studies of diet and energy expenditure in premanifest HD may provide data for interventions to modify specific components of diet that may delay the onset of HD.

In this paper the author presents research into the role of religion in the modern world and attempts to answer the question why students should know about religion, and particularly why religion should be taught in schools. He also presents research into young people’s perspectives on the role of religion in European school systems while at the same time offering a justification for compulsory Religious Education. The arguments are based on international and European legislation, experiences of different countries and the findings of two different researches in Greece published for the first time. Furthermore, the author offers a proposal for compulsory Religious Education which is necessarily based on the constructivist theory according to pedagogical practice in Europe. Finally, the paper stresses the existence of the right to withdraw from Religious Education and the author illustrates the consequences of such a practice.

This article concerns two recent political legislative moves by the Greek government and one in regard to Religious Education (RE) in schools. The latter concerns compulsory RE and the right to exemption for Orthodox students. The former concerns the new Curriculum of compulsory education (2011) which keeps RE as a distinctive compulsory subject for all, claiming that RE has been non-confessional since 2003 and an Amendment (2013) of Law 3536/2007 which was never implemented. The Amendment enacts a formal Muslim RE only for the schools of Western Thrace and for the students of the Muslim Minority who register at Greek public schools and have the right to withdraw from RE due to reasons relating to their religious consciousness. The native Muslims of Western Thrace (a region in the northern part of Greece bordering Turkey) are recognized as a minority according to the Lausanne Treaty (1923). They comprise 50% of the population, and according to the Treaty they have their own religion and educational system. The author takes into account the complexity of religion, educationand politics in the region and addresses controversial issues on the topic of RE that have been raised not only in local society but also between academics, educationists and educators. The question arises as to whether the Greek State is really concerned with RE and the type of RE to be offered to children. Fieldwork by interviewing persons responsible for or related to the subject and articles of local and national newspapers provided the sources for the paper.

PURPOSE: The purpose of this study was to present a fatal case of fulminant hepatitis B (FHB) that developed in a renal transplant recipient, immunized against hepatitis B, 1 year post transplantation. METHODS: Polymerase chain reaction amplification and full genome sequencing were performed to investigate whether specific mutations were associated with hepatitis B virus (HBV) transmission and FHB. RESULTS: Molecular analysis revealed multiple mutations in various open reading frames of HBV, the most important being the G145R escape mutation and a frameshift mutation-insertion (1838insA) within the pre-C/C reading frame. CONCLUSIONS: Our results highlight the possibility of developing FHB, despite previous immunization against HBV or administration of hyperimmune gammaglobulin, because of the selection of escape virus mutants. The current literature and guidelines regarding renal transplantation from hepatitis B surface antigen (HBsAg)-positive to HBsAg-negative patients were also reviewed.

Despite the fact that a significant percentage of the population is unable to swallow tablets and capsules, these dosage forms continue to be the default standard. These oral formulations fail many patients, especially children, because of large tablet or capsule size, poor palatability, and lack of correct dosage strength. The clinical result is often lack of adherence and therapeutic failure. The American Association of Pharmaceutical Scientists formed a Pediatric Formulations Task Force, consisting of members with various areas of expertise including pediatrics, formulation development, clinical pharmacology, and regulatory science, in order to identify pediatric, manufacturing, and regulatory issues and areas of needed research and regulatory guidance. Dosage form and palatability standards for all pediatric ages, relative bioavailability requirements, and small batch manufacturing capabilities and creation of a viable economic model were identified as particular needs. This assessment is considered an important first step for a task force seeking creative approaches to providing more appropriate oral formulations for children.

The mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation that is often deregulated in cancer. Inhibitors of mTOR, including rapamycin and its analogues, are being evaluated as antitumor agents. For their promise to be fulfilled, it is of paramount importance to identify the mechanisms of resistance and develop novel therapies to overcome it. Given the emerging role of microRNAs (miRNAs) in tumorigenesis, we hypothesized that miRNAs could play important roles in the response of tumors to mTOR inhibitors. Long-term rapamycin treatment showed extensive reprogramming of miRNA expression, characterized by up-regulation of miR-17-92 and related clusters and down-regulation of tumor suppressor miRNAs. Inhibition of members of the miR-17-92 clusters or delivery of tumor suppressor miRNAs restored sensitivity to rapamycin. This study identifies miRNAs as new downstream components of the mTOR-signaling pathway, which may determine the response of tumors to mTOR inhibitors. It also identifies potential markers to assess the efficacy of treatment and provides novel therapeutic targets to treat rapamycin-resistant tumors.

The role of thalidomide, bortezomib and lenalidomide in multiple myeloma patients presenting with renal impairment was evaluated in 133 consecutive newly diagnosed patients who were treated with a novel agent-based regimen. A significant improvement of renal function (≥renalPR (renal partial response)) was observed in 77% of patients treated with bortezomib, in 55% with thalidomide and in 43% with lenalidomide (P=0.011). In multivariate analysis, bortezomib-based therapy was independently associated with a higher probability of renal response compared with thalidomide-or lenalidomide-based therapy. Other important variables included eGFR (estimated glomerular filtration rate) ≥30 ml/min, age ≤65 years and myeloma response. Patients treated with bortezomib achieved at least renalPR in a median of 1.34 months vs 2.7 months for thalidomide and >6 months for lenalidomide-treated patients (P=0.028). In multivariate analysis bortezomib-based therapy, higher doses of dexamethasone (≥160 mg during the first month of treatment), an eGFR ≥30 ml/min and age ≤65 years were independently associated with shorter time to renal response. In conclusion, bortezomib-based therapies may be more appropriate for the initial management of patients with myeloma-related renal failure; however, thalidomide and lenalidomide are also associated with significant probability of improvement of their renal function. © 2013 Macmillan Publishers Limited All rights reserved.

New paleomagnetic data from Early Miocene to Pliocene terrestrial sedimentary and volcanic rocks in Central Greece constrain the history of vertical-axis rotation along the central part of the western limb of the Aegean arc. The present-day pattern of rapid block rotation within a broad zone of distributed deformation linking the right-lateral North Anatolian and Kephalonia continental transform faults initiated after Early Pliocene time, resulting in a uniform clockwise rotation of 24.3±6.5° over a region >250 km long and >150 km wide encompassing Central Greece and the western Cycladic archipelago. Because the published paleomagnetic dataset requires clockwise rotations of >50° in Western Greece after ∼17 Ma, while our measurements resolve no vertical-axis rotation of Central Greece between ∼15 Ma and post-Early Pliocene time, a large part of the clockwise rotation of Western Greece must have occurred during the main period of contraction within the external thrust belt of the Ionian Zone between ∼17 and ∼15 Ma. Pliocene initiation of rapid clockwise rotation in Central and Western Greece reflects the development of the North Anatolia–Kephalonia Fault system within the previously extended Aegean Sea region, possibly in response to entry of dense oceanic lithosphere of the Ionian Sea into the Hellenic subduction zone and consequent accelerated slab rollback. The development of the Aegean geometric arc therefore occurred in two short-duration pulses characterized by rapid rotation and strong regional deformation.

Purpose: There is a controversy in the literature regarding the role and the prognostic significance of serum markers in uterine carcinosarcomas (CSs). We attempted to determine the utility of serum CA 125, CA 15-3, CA 19-9, and CEA as prognostic factors and disease follow-up in patients with CS of the uterus. Methods: Thirty-seven patients with CS of the uterus were included in this study. Information regarding demographic, clinical, pathologic, tumor marker data (CA 125, CA 19-9, CA 15-3, and CEA both pre- and postoperatively) treatment and outcome information was obtained, followed by Statistical analysis. Results: The mean follow-up period was 3.5 years. None of the study serum markers showed significant association with the outcome. Greater hazard was found for cases that staged from IIIA to IV compared to those staged from IA to IIB (HR = 4.75, 95 % CI: 1.99-11.3). Also, greater hazard was found for adenosquamous histological type compared to the other histological types. When multiple Cox regression analysis with stepwise approach was implied, it indicated stage as the only significant factor for the outcome. Elevated CA19-9 was more frequent in cases with heterologous sarcoma (p = 0.036). Conclusion: In this retrospective study, none of the preoperative serum tumor markers, neither epithelial component, histological type, nor grade showed a significant association with prognosis. This null finding may have significant implications in the common clinical practice; given that there is a controversy in the literature regarding the role and the significance of the prognostic significance of serum CEA, CA 125, CA 19-9, and CA 15-3. © 2012 Springer-Verlag.

OBJECTIVE: Previous few studies have shown that resistin is significantly elevated in breast cancer (BC) patients. Therefore, we investigated whether serum resistin could be used as a potential diagnostic and prognostic tool for postmenopausal BC (PBC), taking into account clinicopathological features, serum tumor markers, anthropometric, metabolic, and, for the first time, inflammatory parameters. METHODS: Serum resistin, tumor markers (CA 15-3 and CEA), metabolic, anthropometric and inflammatory parameters (TNF-α, IL-6, hsCRP) were determined in 103 postmenopausal women with incident, pathologically confirmed, invasive BC, 103 controls matched on age and time of diagnosis, and 51 patients with benign breast lesions (BBL). RESULTS: Mean serum resistin was significantly higher in cases than in controls and patients with BBL (p<0.001). In patients, resistin was significantly associated with tumor and inflammatory markers, cancer stage, tumor size, grade and lymph node invasion but not with anthropometric, metabolic parameters and hormone receptor status. Multivariable regression analysis revealed that serum IL-6 (p=0.02) and cancer stage (p=0.048) were the strongest determinants of serum resistin in cases adjusting for demographic, metabolic and clinicopathological features. Although resistin's diagnostic performance was low based on ROC curve analysis [0.72, 95% CI: 0.64-0.79], it could, however, represent a BC biomarker reflecting advanced disease stage and inflammatory state. CONCLUSION: Further prospective and longitudinal studies are needed to evaluate whether serum resistin could be used as a prognostic tool in BC monitoring and management. More research is essential to elucidate resistin's ontological role in the association between obesity, representing a chronic low-grade subclinical inflammation, and PBC.

In elderly patients, exposure to antipsychotic medication and subsequent withdrawal may lead to the development of persistent extrapyramidal symptoms, possibly including a syndrome suggested to be tardive parkinsonism. We describe a case in which withdrawal of antipsychotics was unexpectedly associated with progressive deterioration, rather than improvement, of extrapyramidal parkinsonian symptoms. Abnormal imaging of presynaptic dopamine transporters (DaTs) using single-photon emission computed tomography (SPECT) with ioflupane I 123 (DaTscan) substantially contributed to the differential diagnosis, suggesting it was likely that the patient had an underlying neurodegenerative disorder that preceded the onset of medicationinduced parkinsonian symptoms. Our report illustrates how novel findings from DaTscan may assist with diagnosing the cause of persistent parkinsonian symptoms after antipsychotic withdrawal and provide insight into the controversial concept of tardive parkinsonism.

Sex differences in the visual system have been reported in aspects of human vision, such as color perception, peripheral vision and even in the activation of the primary visual cortex. Similarly sex differences have been identified in the visual system of laboratory animals such as monkeys and rats. On the other hand, environmental enrichment (EE) has long been known to affect visual tissues. Taking into consideration the variation in the experimental approaches concerning EE and the sex differences in the visual system, we investigated in male and female rats the serotonergic and dopaminergic effects of EE in the retina and the visual cortex at different time points (i.e. P0-25, P0-P90 and P90-P150). Early EE in adulthood increased the serotonergic activity of the male visual cortex and the female retina (P0-P90). In addition early enrichment (P0-P90) increased dopaminergic activity in the female retina and in the visual cortex of both sexes. Late enrichment increased the serotonergic activity in the retina and visual cortex of both sexes (P90-P150), but increased the dopaminergic activity in the visual cortex only in male animals. In the present study we expose marked sex differences in the neurochemistry of visual tissues and we demonstrate for the first time that EE can in fact modify the serotonergic and dopaminergic neurotransmission in the retina and visual cortex. Overall, the present study underpins the sex-dependent neurochemical status of the visual system and provides insights into the different mechanisms underlying visual processing in the two sexes.

Sex differences in the visual system have been reported in aspects of human vision, such as color perception, peripheral vision and even in the activation of the primary visual cortex. Similarly sex differences have been identified in the visual system of laboratory animals such as monkeys and rats. On the other hand, environmental enrichment (EE) has long been known to affect visual tissues. Taking into consideration the variation in the experimental approaches concerning EE and the sex differences in the visual system, we investigated in male and female rats the serotonergic and dopaminergic effects of EE in the retina and the visual cortex at different time points (i.e. P0-25, P0-P90 and P90-P150). Early EE in adulthood increased the serotonergic activity of the male visual cortex and the female retina (P0-P90). In addition early enrichment (P0-P90) increased dopaminergic activity in the female retina and in the visual cortex of both sexes. Late enrichment increased the serotonergic activity in the retina and visual cortex of both sexes (P90-P150), but increased the dopaminergic activity in the visual cortex only in male animals. In the present study we expose marked sex differences in the neurochemistry of visual tissues and we demonstrate for the first time that EE can in fact modify the serotonergic and dopaminergic neurotransmission in the retina and visual cortex. Overall, the present study underpins the sex-dependent neurochemical status of the visual system and provides insights into the different mechanisms underlying visual processing in the two sexes.

Pineios River is the 3 rd longest river in Peloponnese and flows in Kyllini wider area which is located close to the Hellenic Arc-Trench system. This is one of the most seismically and tectonically active regions in Greece with a great number of changes in the morphogenetic events taking place during the neotectonic period, as well as the last 100 ky. Prior to the 18 th century A.D., the lower alluvial Pineios River flowed north of the Kyllini peninsula and into the Ionian Sea southwest of Kotichi Lagoon, but the river now flows southward into a deltaic swamp and dune region, burying a former lagoon-barrier coastal zone. From this, it becomes apparent that this river is not monotonous in appearance and therefore is not completely controlled by hydrology and hydraulics. In fact, the lower alluvial Pineios River has reacted to major geological controls, surface deformation and uplift movements caused by the activity of the recently mapped Pineios normal fault zone and salt tectonics in Kyllini peninsula resulting in the river flow diversion from north to south at completely different open sea areas. The effects of the geological, tectonic and neotectonic activity and the impact of the human presence and influence on the lower Pineios River are presented in this paper in order to determine the causes of the diversion of the lower (alluvial) Pineios River (NW Peloponnese, Greece) and shoreline displacements.

This study investigated the changes in oxidative stress biomarkers and antioxidant status indices caused by a 3-week high-intensity interval training (HIT) regimen. Eight physically active males performed three HIT sessions/week over 3. weeks. Each session included four to six 30-s bouts of high-intensity cycling separated by 4. min of recovery. Before training, acute exercise elevated protein carbonyls (PC), thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPX) activity, total antioxidant capacity (TAC) and creatine kinase (CK), which peaked 24. h post-exercise (252 ± 30%, 135 ± 17%, 10 ± 2%, 85 ± 14% and 36 ± 13%, above baseline, respectively; p<. 0.01), while catalase activity (CAT) peaked 30. min post-exercise (56 ± 18% above baseline; p<. 0.01). Training attenuated the exercise-induced increase in oxidative stress markers (PC by 13.3 ± 3.7%; TBARS by 7.2 ± 2.7%, p<. 0.01) and CK activity, despite the fact that total work done was 10.9 ± 3.6% greater in the post- compared with the pre-training exercise test. Training also induced a marked elevation of antioxidant status indices (TAC by 38.4 ± 7.2%; CAT by 26.2 ± 10.1%; GPX by 3.0 ± 0.6%, p<. 0.01). Short-term HIT attenuates oxidative stress and up-regulates antioxidant activity after only nine training sessions totaling 22. min of high intensity exercise, further supporting its positive effect not only on physical conditioning but also on health promotion. © 2013 Elsevier Ltd.

This study investigated the changes in oxidative stress biomarkers and antioxidant status indices caused by a 3-week high-intensity interval training (HIT) regimen. Eight physically active males performed three HIT sessions/week over 3. weeks. Each session included four to six 30-s bouts of high-intensity cycling separated by 4. min of recovery. Before training, acute exercise elevated protein carbonyls (PC), thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPX) activity, total antioxidant capacity (TAC) and creatine kinase (CK), which peaked 24. h post-exercise (252 ± 30%, 135 ± 17%, 10 ± 2%, 85 ± 14% and 36 ± 13%, above baseline, respectively; p<. 0.01), while catalase activity (CAT) peaked 30. min post-exercise (56 ± 18% above baseline; p<. 0.01). Training attenuated the exercise-induced increase in oxidative stress markers (PC by 13.3 ± 3.7%; TBARS by 7.2 ± 2.7%, p<. 0.01) and CK activity, despite the fact that total work done was 10.9 ± 3.6% greater in the post- compared with the pre-training exercise test. Training also induced a marked elevation of antioxidant status indices (TAC by 38.4 ± 7.2%; CAT by 26.2 ± 10.1%; GPX by 3.0 ± 0.6%, p<. 0.01). Short-term HIT attenuates oxidative stress and up-regulates antioxidant activity after only nine training sessions totaling 22. min of high intensity exercise, further supporting its positive effect not only on physical conditioning but also on health promotion. © 2013 Elsevier Ltd.

This study investigated the changes in oxidative stress biomarkers and antioxidant status indices caused by a 3-week high-intensity interval training (HIT) regimen. Eight physically active males performed three HIT sessions/week over 3. weeks. Each session included four to six 30-s bouts of high-intensity cycling separated by 4. min of recovery. Before training, acute exercise elevated protein carbonyls (PC), thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPX) activity, total antioxidant capacity (TAC) and creatine kinase (CK), which peaked 24. h post-exercise (252 ± 30%, 135 ± 17%, 10 ± 2%, 85 ± 14% and 36 ± 13%, above baseline, respectively; p<. 0.01), while catalase activity (CAT) peaked 30. min post-exercise (56 ± 18% above baseline; p<. 0.01). Training attenuated the exercise-induced increase in oxidative stress markers (PC by 13.3 ± 3.7%; TBARS by 7.2 ± 2.7%, p<. 0.01) and CK activity, despite the fact that total work done was 10.9 ± 3.6% greater in the post- compared with the pre-training exercise test. Training also induced a marked elevation of antioxidant status indices (TAC by 38.4 ± 7.2%; CAT by 26.2 ± 10.1%; GPX by 3.0 ± 0.6%, p<. 0.01). Short-term HIT attenuates oxidative stress and up-regulates antioxidant activity after only nine training sessions totaling 22. min of high intensity exercise, further supporting its positive effect not only on physical conditioning but also on health promotion. © 2013 Elsevier Ltd.

We fabricated a silicon-wafer based p-n junction solar cell with conversion efficiency of 11% without conventional doping of the emitter or the use of anti-reflecting coatings. The emitter was originally nanocrystalline, grown on n-type crystalline Si and covered with a thin semi-transparent Al layer. Annealing in nitrogen at 430 °C promoted a simultaneous aluminum (Al)-induced recrystallization and Al-doping of the emitter. The recrystallized emitter consisted of considerably larger Si grains which were epitaxially crystallized on the Si substrate. These two effects led to a considerable improvement of the electrical and photovoltaic properties of the resulting p-n junction. © 2013 AIP Publishing LLC.

BACKGROUND: Psoriasis is associated with a variety of comorbidities such as obesity and cardiovascular disease. OBJECTIVE: In a cross-sectional study, we explored whether obstructive sleep apnea and hypopnea syndrome (OSAHS) is associated with psoriasis characteristics and metabolic parameters. METHODS: Thirty-five patients with chronic plaque psoriasis underwent a nocturnal polysomnography study and were analysed for Apnoea-Hypopnoea Index to assess OSAHS severity and Framigham score to predict the absolute risk of coronary artery disease at 10 years. The association of OSAHS with psoriasis was examined according to psoriasis characteristics (PASI and DLQI scores, disease duration and previous use of systemic treatments), metabolic parameters (Body Mass Index - BMI, waist to hip ratio - WHR, lipid profile) and other comorbidities (obesity, hypertension, arthritis and cardiovascular disease). RESULTS: There was no correlation between psoriasis characteristics and OSAHS. Psoriasis patients with OSAHS presented more frequent snoring and lower sleep quality compared with those without OSAHS. In univariate analyses, OSAHS was associated with increased BMI and hypertension in psoriasis patients. In multivariable logistic regression models, there was statistically significant evidence that only BMI and hypertension were associated with increased risk of OSAHS, adjusting for psoriasis characteristics, age and gender. Presence of metabolic syndrome, WHR, and smoking were not significant risk factors for OSAHS. In subgroup analyses, OSAHS correlated with duration of psoriasis (>8 years) in women (P = 0.021) and with Framigham score in men (P = 0.035). CONCLUSION: OSAHS may be a comorbidity in obese psoriasis patients with hypertension. Treatment with continuous positive airway pressure and weight loss interventions should be initiated.

Given a singular foliation, we attach an “essential isotropy” group to each of its leaves, and show that its discreteness is the integrability obstruction of a natural Lie algebroid over the leaf. We show that a condition ensuring discreteness is the local surjectivity of a transversal exponential map associated with the maximal ideal of vector fields prescribed to be tangent to the foliation. The essential isotropy group is also shown to control the smoothness of the holonomy cover of the leaf (the associated fiber of the holonomy groupoid), as well as the smoothness of the associated isotropy group. Namely, the (topological) closeness of the essential isotropy group is a necessary and sufficient condition for the holonomy cover to be a smooth (finite-dimensional) manifold and the isotropy group to be a Lie group. These results are useful towards understanding the normal form of a singular foliation around a compact leaf. At the end of this article we briefly outline work of ours on this normal form, to be presented in a subsequent paper.

Although there is a substantial body of research on loneliness in children and adolescents, there is relatively less research evidence on solitude, as a state of being alone, and more specifically, on facets of solitude such as attitude toward aloneness, ability to be alone, and positive aloneness. In this paper, after some conceptual clarifications, research is reviewed on understanding the nature of solitude; affect of time alone; attitude toward aloneness; the links between solitude and adjustment; and the associations between solitude and other aloneness concepts. Finally, suggestions for future research on solitude in childhood and adolescence are offered.

We aimed to determine the second-trimester amniotic fluid (AF) levels of soluble Fas (sFas) and Fas-ligand (FasL) and investigate their association with fetal growth. Therefore, sFas and FasL levels were measured by enzyme immunoassay in the AF of 21 small for gestational age (SGA), 13 large for gestational age (LGA), and 44 appropriate for gestational age (AGA) fetuses of pregnant women who underwent amniocentesis at between 15 and 22 weeks gestation. Our study results showed that sFas and FasL levels were detectable in AF. sFAS median (25th-75th centile) levels were 3.8 (2.8-4.6). ng/ml in SGA, 3.6 (3.1-4.5). ng/ml in AGA, and 4.0 (3.1-4.4). ng/ml in LGA. FasL median (25th-75th centile) levels were 26.0 (20.3-32.7). pg/ml in SGA, 22.7 (18.4-28.5). pg/ml in AGA, and 21.5 (15.8-30.9). pg/ml in LGA. The differences were not statistically significant. Nevertheless, statistically significant differentiation of FasL levels existed when SGA fetuses in the extremes of distribution (≤5th, ≤2.5th centile) were considered. This is the first study presenting sFas and FasL concentrations in early second-trimester amniotic fluid in AGA, SGA, and LGA fetuses. We found indications that severe and very severe SGA fetuses (≤5th and ≤2.5th centile) have high levels of FasL in the amniotic fluid. This finding probably reflects the increased rate of apoptosis that is assumed to exist in cases of extreme growth restriction. © 2013 Elsevier Ireland Ltd.

We approach the problem of bulk acceleration in relativistic, cold, magnetized outflows, by solving the momentum equation along the flow, a.k.a. the wind equation, under the assumptions of steady-state and axisymmetry. The bulk Lorentz factor of the flow depends on the geometry of the field/streamlines and by extension, on the form of the "bunching function" S=r^2 B_p/ A, where r is the cylindrical distance, B_p the poloidal magnetic field, and A the magnetic flux function. We investigate the general characteristics of the S function and how its choice affects the terminal Lorentz factor gamma_f and the acceleration efficiency gamma_f/mu, where mu is the total energy to mass flux ratio (which equals the maximum possible Lorentz factor of the outflow). Various fast-rise, slow-decay examples are selected for S, each one with a corresponding field/streamlines geometry, with a global maximum near the fast magnetosonic critical point, as required from the regularity condition. As it is proved, proper choices of S can lead to efficiencies greater than 50%. Last, we apply our results to the momentum equation across the flow, in an effort to estimate their validity, as well as identifying the factors that lead to an accurate full-problem solution. The results of this work, depending on the choices of the flow integral mu, can be applied to relativistic GRB or AGN jets.