Publications by Year: 2016

We present 106 times of minima of 27 eclipsing binaries.

We present 107 times of minima of 19 eclipsing binaries.

Cytosolic GIVA phospholipase A2 (GIVA cPLA2) initiates the eicosanoid pathway of inflammation and thus inhibitors of this enzyme constitute novel potential agents for the treatment of inflammatory diseases. Traditionally, GIVA cPLA2 inhibitors have suffered systemically from high lipophilicity. We have developed a variety of long chain 2-oxoamides as inhibitors of GIVA PLA2. Among them, AX048 was found to produce a potent analgesic effect. We have now reduced the lipophilicity of AX048 by replacing the long aliphatic chain with a chain containing an ether linked aromatic ring with in vitro inhibitory activities similar to AX048.

The study "3,000 Years of East Mediterranean Sea Levels" investigates whether trends observed during this period in Israel from archaeological indications can be corroborated and strengthened by comparing them with relative sea levels observed in Greece. The process is comprised of three questions: 1) What types of archaeological sea-level indicators in Greece and Israel have the highest level of reliability for dating and sea-level evaluation? 2) What are the overall trends of sea-level change in Greece and Israel during the last 3,000 years, and what degree of error do these curves have? 3) What if any regional trends can be identified from the combined Greek and Israeli data? To answer the above questions, three objectives are pursued: 1) Identify archaeological RSL indicators of the last 3,000 years in Israel and Greece, including already published indicators with adequate measurements, those published but in need of new measurements, and unpublished potential indicators. 2) Assess the reliability of indicators using a consistent scoring system, correction for isostatic and tectonic effects, more precise measurements from indicators, and by exploring new methods to determine the chronology of rock carved indicators in Israel. 3) Using the assembled data, create a sea-level reconstruction for Greece, and combine the data with existing reconstructions from Israel for an analysis of matching trends. The study began with research of published sources and was supplemented by field activity. Surveys in Greece including Crete to assess both published and potential indicators occurred. Ruins from Chersonisos and Matala in Crete were examined and new measurements were taken from the latter. Fieldwork was also performed in Israel, including measurements from Caesarea for functional elevations on water channels at the promontory palace pool, at Achziv's fishpond, and around Tel Dor. The survey collected nearly 140 indicators from Israel and about 120 from Greece (excluding those outside the project's chronological scope). Of the Israeli indicators, some 120 were deemed reliable enough for reconstructions, whereas in Greece only 40 were, and not all of these from tectonically stable areas. The higher reliability of the Israeli dataset may stem from a smaller coastline and more focused sea-level research over the past few decades. In Greece, many measurements were taken by archaeologists in the 20th century before precise surveying methods were available, and published without sufficient metadata. Since then some of the sites have also become inaccessible to sea-level researchers. Analysis of indicators revealed gaps and disparities between the two regional datasets. Israel has a very strong set of many indicators from the Roman Period (~2000BP) to present, but fewer from 3000-2000BP. Greek indicators are strongly clustered in the Classical and Hellenistic Periods (2500-2000BP) with fewer before or after. These disparities make it difficult to effectively compare sea level between regions, but results suggest some correspondence of the curves. Analysis supports the work of previous Israeli researchers and suggests a relatively stable sea level there for the last 2000 years, with possible fluctuations not exceeding half a meter above or below current sea level at ~1500BP and ~750BP respectively. Both regions indicate a sea level rise between 2500-2000BP, but more data from Israel is needed to confirm this, while data from 3000-2500BP in Israel and Greece alike is scarce. In addition to the overall regional RSL comparisons, the current study also identifies the need for ongoing research and data collection: Continuing the search for sea-level indicators in Israel from 3000-2000BP, and in Greece from 3000-2500BP and from 2000BP to present, particularly in areas of reported tectonic stability like the Cyclades.

Strong motion data recorded during the 15-year operation of the CORinth Gulf Soft Soil Array (CORSSA) in the highly seismic region of Aegion have been homogenized and organized in a MySQL database. In the present work we describe the contents of the database and the web portal through which these data are publicly accessible. CORSSA comprises one surface and four downhole 3-D broadband accelerometric stations. It was installed in 2002, in the framework of European project CORSEIS, aiming at gathering data for studying site effects, liquefaction, and non-linear behaviour of soils, as well as earthquake source properties. To date, the array has recorded 549 local and regional events with magnitudes ranging from 1.1 to 6.5. Although the vast majority of the recorded events caused weak ground motion at the CORSSA site, the scientific value of the data set pertains to the sparsity of this kind of infrastructure in most parts of the world.

Background The work is part of a wider research project wherein we are trying to further explore the conceptual ecology of evolutionary theory of present and prospective teachers in Greece. Methods Quantitative and qualitative research was applied. In the former a questionnaire was answered by 318 secondary school teachers who teach biology. We further interviewed eight of the teachers by means of semi structured interviews and analyzed the interviews using the QSR nVivo program. Results Acceptance of evolution levels was found moderate both in the total cohort and among science teachers; on the one hand, this was correlated with the prevalence of low level of knowledge and understanding due to lack of previous instruction; on the other hand, their type of religiosity was not a serious obstacle to accepting evolution, since it was correlated with a high degree of thinking dispositions. Conclusions The results are in agreement with our previous findings that the type of religiosity is crucial for the acceptance or rejection of evolution, particularly when it does not prevent someone from being “open-minded”. At the same time, the fact that geologists who teach science showed the highest level of acceptance of evolution, indicates, when paired with other evidence, that the geological data are the most convincing evidence to help students and teachers to make a first step in their multistep route towards accepting and understanding the theory of evolution.

BACKGROUND: Accreditation is a valuable resource for medical laboratories. The development of quality systems based on ISO 15189 has taken place in many laboratories in the European countries but data about accreditation remain scarce. The EFLM Working Group "Accreditation and ISO/CEN standards" conducted a survey that reviews the current state of the accreditation process in European countries. METHODS: An on-line questionnaire was addressed to delegates of 39 EFLM scientific societies in March 2014. One answer by country was taken into account. The survey was dealing with mandatory status, number of accredited medical laboratories in each country, possibility of flexible scope and concerned medical fields. The status of point-of-care testing (POCT) in each country was also studied. RESULTS: Twenty-nine responses (74%) were registered. All the assessed countries (100%) have begun an accreditation process in various ways. All the national accreditation bodies (NAB) offer or are working to offer an ISO 15189 accreditation. The accreditation process most often concerns all phases of the examination and various medical fields. Medical laboratories are responsible for POCT in 20 (69%) countries. The accreditation process for POCT, according to ISO 15189 and ISO 22870, is also developing. CONCLUSIONS: While there are several variations in the approaches to accreditation of medical laboratories in the European countries, the ISO 15189 accreditation project has been widely accepted. The use of a unique standard and the cooperation among countries due to scientific societies, EFLM, accreditation bodies and EA enable laboratory professionals to move toward uniform implementation of the accreditation concept

BACKGROUND: Chronic aerobic exercise training is associated with improved endothelial function and arterial stiffness and favourable long-term cardiovascular effects. DESIGN: We investigated the acute effects of continuous moderate intensity aerobic exercise (CAE) and high intensity interval aerobic exercise (hIAE) on endothelial function and arterial stiffness in healthy participants. METHODS: Twenty healthy men were recruited to this cross-over study. They participated in two exercise sessions: (a) CAE, volume at 50% of maximum aerobic work for 30 minutes; and (b) hIAE, interval maximum aerobic work for 30 minutes. Endothelial function was evaluated by flow-mediated dilation in the brachial artery. The carotid femoral pulse wave velocity and the femoral dorsalis pedis pulse wave velocity were measured as indices of central aortic and peripheral arterial stiffness. Measurements were carried out before and immediately after each exercise session. RESULTS: There was no statistically significant difference in the baseline measurements before CAE and hIAE with respect to flow-mediated dilation, the carotid femoral pulse wave velocity and the femoral dorsalis pedis pulse wave velocity (p = NS). Both CAE and hIAE significantly improved the flow-mediated dilation compared with baseline (p < 0.001). Similarly, the femoral dorsalis pedis pulse wave velocity was improved after CAE and hIAE (p < 0.005), whereas the carotid femoral pulse wave velocity was not significantly affected (p = NS). CONCLUSION: Both CAE and hIAE can favourably affect endothelial function, suggesting another cardioprotective effect of acute exercise. These types of aerobic exercise have a different impact on the central and peripheral arterial stiffness.

OBJECTIVES: Whilst physical activity is linked to cardiovascular health, it has lately been recognized that different types of exercise exert diverse effects on the cardiovascular system. Therefore, we investigated the acute effects of continuous moderate-intensity aerobic exercise (CAE) and high-intensity interval aerobic exercise (hIAE) on arterial function and inflammation. METHODS: Twenty healthy men (mean age 22.6 ± 3.3 years) were recruited in this crossover study. Each of the 20 volunteers participated in two separate sessions (hIAE and CAE). The augmentation index (AIx) of aortic pressure waveforms and serum levels of interleukin-17 (IL-17) were measured before and after each exercise session. RESULTS: There were no significant differences in baseline hemodynamic and inflammatory measurements before CAE and hIAE. Compared to baseline, AIx was significantly improved after CAE (p = 0.04), while there was no significant change after hIAE (p = 0.65). Serum levels of IL-17 were significantly elevated after CAE (p = 0.042), while hIAE had no significant effect on IL-17 levels (p = 0.47). Interestingly, there was an inverse association between the elevation of IL-17 levels and the AIx improvement after CAE (p = 0.05). CONCLUSION: These findings provide additional evidence concerning the cardiovascular effects of different types of exercise training through modification of peripheral hemodynamics and the inflammatory process.

Tsoukos, A, Bogdanis, GC, Terzis, G, and Veligekas, P. Acute improvement of vertical jump performance after isometric squats depends on knee angle and vertical jumping ability. J Strength Cond Res 30(8): 2250-2257, 2016-This study examined the acute effects of maximum isometric squats at 2 different knee angles (90 or 140°) on countermovement jump (CMJ) performance in power athletes. Fourteen national-level male track and field power athletes completed 3 main trials (2 experimental and 1 control) in a randomized and counterbalanced order 1 week apart. Countermovement jump performance was evaluated using a force-plate before and 15 seconds, 3, 6, 9, and 12 minutes after 3 sets of 3 seconds maximum isometric contractions with 1-minute rest in between, from a squat position with knee angle set at 90 or 140°. Countermovement jump performance was improved compared with baseline only in the 140° condition by 3.8 ± 1.2% on the 12th minute of recovery (p = 0.027), whereas there was no change in CMJ height in the 90° condition. In the control condition, there was a decrease in CMJ performance over time, reaching -3.6 ± 1.2% (p = 0.049) after 12 minutes of recovery. To determine the possible effects of baseline jump performance on subsequent CMJ performance, subjects were divided into 2 groups ("high jumpers" and "low jumpers"). The baseline CMJ values of "high jumpers" and "low jumpers" differed significantly (CMJ: 45.1 ± 2.2 vs. 37.1 ± 3.9 cm, respectively, p = 0.001). Countermovement jump was increased only in the "high jumpers" group by 5.4 ± 1.4% (p = 0.001) and 7.4 ± 1.2% (p = 0.001) at the knee angles of 90 and 140°, respectively. This improvement was larger at the 140° angle (p = 0.049). Knee angle during isometric squats and vertical jumping ability are important determinants of the acute CMJ performance increase observed after a conditioning activity.

Mountain Ainos is the highest mountain of the Ionian Islands with a maximum elevation of 1628 m. Its National Park is characterized by rich flora including endemic species such as Greek fir. In order to exploit fully its touristic potential, it is necessary to examine the mountain climate. However in situ measurements of climatic parameters in mountain areas pose difficulties as far as to access areas of interest. The current study addresses one specific object: Estimating the air temperature at different altitudes of the southeastern side of Mt. Ainos, having air temperature data at the exact same altitudes of the northwestern side which is more easily accessible. We performed linear regression analysis to estimate the mean, maximum and minimum daily air temperature of the southeastern sites from data measured at the northwestern one. The results are considered satisfactory in air temperature estimation at all examined altitudes. More accurate estimations were provided in the case of the mean air temperature at the altitude of 1580 m. Also, linear models indicated noticeable estimations of the minimum temperatures at 1300 and 1580 m.

Using CO (4-3) and (2-1) Atacama Large Millimeter Array (ALMA) data, we prove that the molecular gas in the jet-driven winds of the galaxy IC 5063 is more highly excited than the rest of the molecular gas in the disk of the same galaxy. On average, the CO(4 - 3) /CO(2 - 1) flux ratio is 1 for the disk and 5 for the jet accelerated or impacted gas. Spatially-resolved maps reveal that in regions associated with winds, the CO(4 - 3) /CO(2 - 1) flux ratio significantly exceeds the upper limit of 4 for optically thick gas. It frequently takes values between 5 and 11, and it occasionally further approaches the upper limit of 16 for optically thin gas. Excitation temperatures of 30-100 K are common for the molecules in these regions. If all of the outflowing molecular gas is optically thin, at 30-50 K, then its mass is 2 × 106 M☉. This lower mass limit is an order of magnitude below the mass derived from the CO(2 - 1) flux in the case of optically thick gas. Molecular winds can thus be less massive, but more easily detectable at high z than they were previously thought to be.

Using CO (4-3) and (2-1) Atacama Large Millimeter Array (ALMA) data, we prove that the molecular gas in the jet-driven winds of the galaxy IC 5063 is more highly excited than the rest of the molecular gas in the disk of the same galaxy. On average, the CO(4 - 3) /CO(2 - 1) flux ratio is 1 for the disk and 5 for the jet accelerated or impacted gas. Spatially-resolved maps reveal that in regions associated with winds, the CO(4 - 3) /CO(2 - 1) flux ratio significantly exceeds the upper limit of 4 for optically thick gas. It frequently takes values between 5 and 11, and it occasionally further approaches the upper limit of 16 for optically thin gas. Excitation temperatures of 30-100 K are common for the molecules in these regions. If all of the outflowing molecular gas is optically thin, at 30-50 K, then its mass is 2 × 106 M⊙. This lower mass limit is an order of magnitude below the mass derived from the CO(2 - 1) flux in the case of optically thick gas. Molecular winds can thus be less massive, but more easily detectable at high z than they were previously thought to be.

The fatiguing effect of long-distance running has been examined in the context of a variety of parameters. However, there is scarcity of data regarding its effect on the vertical jump mechanics. The purpose of this study was to investigate the alterations of countermovement jump (CMJ) mechanics after a half-marathon mountain race. Twenty-seven runners performed CMJs before the race (Pre), immediately after the race (Post 1) and five minutes after Post 1 (Post 2). Instantaneous and ensemble-average analysis focused on jump height and, the maximum peaks and time-to-maximum peaks of: Displacement, vertical force (Fz), anterior-posterior force (Fx), Velocity and Power, in the eccentric (tECC) and concentric (tCON) phase of the jump, respectively. Repeated measures ANOVAs were used for statistical analysis (p ≤ 0.05). The jump height decrease was significant in Post 2 (-7.9%) but not in Post 1 (-4.1%). Fx and Velocity decreased significantly in both Post 1 (only in tECC) and Post 2 (both tECC and tCON). Α timing shift of the Fz peaks (earlier during tECC and later during tCON) and altered relative peak times (only in tECC) were also observed. Ensemble-average analysis revealed several time intervals of significant post-race alterations and a timing shift in the Fz-Velocity loop. An overall trend of lowered post-race jump output and mechanics was characterised by altered jump timing, restricted anterior-posterior movement and altered force-velocity relations. The specificity of mountain running fatigue to eccentric muscle work, appears to be reflected in the different time order of the post-race reductions, with the eccentric phase reductions preceding those of the concentric one. Thus, those who engage in mountain running should particularly consider downhill training to optimise eccentric muscular action.

Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 - < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 - < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. © 2016 Ferrata Storti Foundation.

BACKGROUND: The anterior component of occlusal force (ACF), considered to result from the mesial inclination of teeth relative to the occlusal plane, has been estimated by indirectly measuring contact point tightness (CPT) through interproximal insertion of metal strips. ACF has been observed concurrently with a posterior component, whose theoretical origin is difficult to explain. OBJECTIVES: Evaluate ACF by measuring CPT directly, and integrate current data to propose a theoretical basis for ACF. MATERIALS AND METHODS: The sample comprised 14 females (age: 22.3±2.8) and 16 males (age: 20.8±2.5). Our device consisted of two force sensors: one for measuring maximum bite force (MBF) (overall thickness: 4mm), and one for measuring CPT directly (0.2mm thick), inserted between the lower first molar and second premolar. ACF was computed as the difference in CPT between the biting (at 75 per cent of MBF) and non-biting conditions. RESULTS: Averages of MBF, CPT, and ACF were 666.67 [standard deviation (SD): 36.06], 6.74 (SD: 1.17), and 20.59 (SD: 4.60) N, respectively. ACF, CPT, and MBF were higher in males by approximately 28, 18 and 7 per cent, respectively. A positive correlation was observed between ACF and MBF (R (2): 0.64). CPT was also significantly correlated to MBF (R (2): 0.40). Biomechanical analysis indicates that previously offered explanations do not unriddle the concurrent increase of CPT at anterior and posterior contact points. CONCLUSIONS: ACF was related to bite force by a logarithmic model. We speculate that CPT increases during biting through a combination of mesial tipping of teeth and mandibular bending.

HIV is responsible for one of the largest viral pandemics in human history. Despite a concerted global response for prevention and treatment, the virus persists. Thus, urgent public health action, utilizing novel interventions, is needed to prevent future transmission events, critical to eliminating HIV. For public health planning to prove effective and successful, we need to understand the dynamics of regional epidemics and to intervene appropriately. HIV molecular epidemiology tools as implemented in phylogenetic, phylodynamic and phylogeographic analyses have proven to be powerful tools in public health planning across many studies. Numerous applications with HIV suggest that molecular methods alone or in combination with mathematical modelling can provide inferences about the transmission dynamics, critical epidemiological parameters (prevalence, incidence, effective number of infections, Re, generation times, time between infection and diagnosis), or the spatiotemporal characteristics of epidemics. Molecular tools have been used to assess the impact of an intervention and outbreak investigation which are of great public health relevance. In some settings, molecular sequence data may be more readily available than HIV surveillance data, and can therefore allow for molecular analyses to be conducted more easily. Nonetheless, classic methods have an integral role in monitoring and evaluation of public health programmes, and should supplement emerging techniques from the field of molecular epidemiology. Importantly, molecular epidemiology remains a promising approach in responding to viral diseases.

Το άρθρο στα αγγλικά περιλαμβάνει τα αποτελέσματα της συζήτησης των μαθητών στην εκδήλωση στο Ευρωπαϊκό Σχολείο ΙΙΙ Βρυξέλλες που πραγματοποιήθηκε στις 11 Μαρτίου 2016.

The objective of the study is to assess the human thermal comfort at a University Campus in the metropolitan area of Athens. The equipment setup consists of all the necessary sensors for human thermal comfort estimation along with a high resolution GPS, mounted on a cargo bicycle. The experiment was carried out for midday and night on July 29, 2015. Besides, long term 5 min measurements from a meteorological station, established on the roof of a building within the University Campus, were also used to quantify the mean thermal environment. The densely carried out bicycle measurements every 5 s was the input data utilized by the ENVI-met model; a three-dimensional microclimate model designed to simulate the surface-plant-air interactions in urban environment. The in situ measurements along with the model's output results reveal the thermal comfort regime of the selected area and the ability of the model to estimate accurately the micrometeorological conditions.

Only a few red dwarf flaring stars in the solar neighbourhood have undergone exceptional events called superflares. They have been detected with high-energy satellites (Swift) and have been proven to be powerful events (both in intensity and energy) and potentially hazardous for any extraterrestial life. The physics of these events can be understood as an extrapolation of the (much) weaker activity already occurring in the most powerful solar flares occurring in the Sun. Nevertheless, the origin (why?) of these superflares occur is currently unknown. A recent study presents the optical and X-ray long-term evolution of the emission by the super-flare from the red-dwarf star DG CVn undertaken in 2 014. In that paper we comment on the context of these observations and on the properties that can be derived through the analysis of them.

We consider the multi-armed bandit problem under a cost constraint. Successive samples from each population are i.i.d. with unknown distribution and each sample incurs a known population-dependent cost. The objective is to design an adaptive sampling policy to maximize the expected sum of n samples such that the average cost does not exceed a given bound sample-path wise. We establish an asymptotic lower bound for the regret of feasible uniformly fast convergent policies, and construct a class of policies, which achieve the bound. We also provide their explicit form under Normal distributions with unknown means and known variances. Copyright © Cambridge University Press 2016

Beachrocks represents a coastal deposition in the intertidal area, and studying their properties may lead to create a model which identifies the conditions of their formation (paleo-environment). This paper focuses most intently on the cement material which is able to recover the paleo-environment conditions during diagenesis of such coastal sediment. We used optical microscopy, secondary electron microscopy and Raman Spectroscopy to characterize the cement texture, mineralogy and chemistry in the beachrocks. The existence of pure calcite primarily controlled by the meteorite water, while Mg-calcite appears between the lower meteoric and the upper marine phreatic zone. Finally, the presence of aragonite associated with the marine phreatic to lower marine vadose environment.

The glycosaminoglycan heparin and its derivatives act strongly on blood coagulation, controlling the activity of serine protease inhibitors in plasma. Nonetheless, there is accumulating evidence highlighting different anticancer activities of these molecules in numerous types of cancer. Nano-heparins may have great biological significance since they can inhibit cell proliferation and invasion as well as inhibiting proteasome activation. Moreover, they can cause alterations in the expression of major modulators of the tumor microenvironment, regulating cancer cell behavior. In the present study, we evaluated the effects of two nano-heparin formulations: one isolated from porcine intestine and the other from the sea squirt Styela plicata, on a breast cancer cell model. We determined whether these nano-heparins are able to affect cell proliferation, apoptosis and invasion, as well as proteasome activity and the expression of extracellular matrix molecules. Specifically, we observed that nano-Styela compared to nano-Mammalian analogue has higher inhibitory role on cell proliferation, invasion and proteasome activity. Moreover, nano-Styela regulates cell apoptosis, expression of inflammatory molecules, such as IL-6 and IL-8 and reduces the expression levels of extracellular matrix macromolecules, such as the proteolytic enzymes MT1-MMP, uPA and the cell surface proteoglycans syndecan-1 and -2, but not on syndecan-4. The observations reported in the present article indicate that nano-heparins and especially ascidian heparin are effective agents for heparin-induced effects in critical cancer cell functions, providing an important possibility in pharmacological targeting.

OBJECTIVE: This paper presents the development of medical informatics education during the years from the establishment of the International Medical Informatics Association (IMIA) until today. METHOD: A search in the literature was performed using search engines and appropriate keywords as well as a manual selection of papers. The search covered English language papers and was limited to search on papers title and abstract only. RESULTS: The aggregated papers were analyzed on the basis of the subject area, origin, time span, and curriculum development, and conclusions were drawn. CONCLUSIONS: From the results, it is evident that IMIA has played a major role in comparing and integrating the Biomedical and Health Informatics educational efforts across the different levels of education and the regional distribution of educators and institutions. A large selection of references is presented facilitating future work on the field of education in biomedical and health informatics.

The biopharmaceutics classification system (BCS) was based on the tube model of the intestinal lumen. This model considers constant drug permeability along the intestines, a plug flow fluid with the suspended drug particles moving with the fluid, and dissolution in the small particle limit. Since then the research work focusing on drug gastrointestinal (GI) absorption phenomena and processes rely on the classical laws of transport, diffusion and kinetics; however, the homogeneous assumptions associated with the well-stirred Euclidean media, where the classical laws of diffusion and kinetics apply, have been questioned in the past In this work we explore the biopharmaceutic classification of drugs using a heterogeneous pseudo steady-state model of oral drug absorption. The fraction of dose absorbed (F-abs) was expressed as a function of two time-dependent processes where time dependent coefficients govern drug absorption and non-absorption processes. Fundamental drug properties like the absorption potential are correlated with F-abs and allow the biopharmaceutic classification of drugs taking into account the heterogeneous aspects of oral drug absorption. This analysis reveals that for Class I drugs no time dependency is expected for both absorption and non absorption processes since the gastric emptying is controlling the absorption of Class I drugs while the completion of absorption (F-abs > 90%) is terminated along the first part of the jejunum. Due to the biopharmaceutical properties of Class II, III and IV drugs, these drugs travel throughout the GI tract and therefore both absorption and non absorption processes will exhibit time dependency. Thus, the calculation of F-abs (<90%) for Class II, III and IV is dependent on the estimates of the time exponents of time dependent coefficients controlling drug absorption e.g. dissolution, uptake or non absorption e.g. precipitation. (C) 2016 Elsevier B.V. All rights reserved.

© 2016 The Menninger Foundation. The purpose of this study was to assess the possible effect of recalled traumatic experiences, perceived parental rearing styles, and family parameters on the occurrence of borderline personality disorder (BPD) versus other personality disorders (other-PDs). A total of 88 adult outpatients with personality disorders completed the Traumatic Antecedents Questionnaire and the Egna Minnen av Barndoms Uppfostran, which measures perceptions regarding parental rearing. Results indicated that incidence of traumatic childhood experiences was higher among those in the BPD group compared to those in the other-PD group. Firstborns were less likely to carry a diagnosis of BPD over other-PDs. Also, significantly more BPD compared to other-PD patients reported being the father's favorite child over siblings. Results suggest that traumatic exper iences, birth order, and family interactions in the presence of siblings seem to differentially affect the formation of borderline diagnosis compared to other-PDs. Limitations and clinical implications of the study are discussed in detail.

Powerful flares from blazars with short (∼min) variability time-scales are challenging for current models of blazar emission. Here, we present a physically motivated ab initio model for blazar flares based on the results of recent particle-in-cell (PIC) simulations of relativistic magnetic reconnection. PIC simulations demonstrate that quasi-spherical plasmoids filled with high-energy particles and magnetic fields are a self-consistent by-product of the reconnection process. By coupling our PIC-based results (I.e. plasmoid growth, acceleration profile, particle and magnetic content) with a kinetic equation for the evolution of the electron distribution function we demonstrate that relativistic reconnection in blazar jets can produce powerful flares whose temporal and spectral properties are consistent with the observations. In particular, our model predicts correlated synchrotron and synchrotron self-Compton flares of duration of several hours-days powered by the largest and slowest moving plasmoids that form in the reconnection layer. Smaller and faster plasmoids produce flares of sub-hour duration with higher peak luminosities than those powered by the largest plasmoids. Yet, the observed fluence in both types of flares is similar. Multiple flares with a range of flux-doubling time-scales (minutes to several hours) observed over a longer period of flaring activity (days or longer) may be used as a probe of the reconnection layer's orientation and the jet's magnetization. Our model shows that blazar flares are naturally expected as a result of magnetic reconnection in a magnetically dominated jet.

Renal failure (RF) is a common and severe complication of symptomatic myeloma, associated with significant morbidity and mortality. Such patients are commonly excluded from clinical trials. Bortezomib/dexamethasone (VD)-based regimens are the backbone of the treatment of newly diagnosed MM patients who present with severe RF even those requiring dialysis. We analyzed the outcomes of 83 consecutive bortezomib-treated patients with severe RF (eGFR<30 ml/min/1.73 m2), of which 31 (37%) required dialysis. By IMWG renal response criteria, 54 (65%) patients achieved at least MRrenal, including CRrenal in 35% and PRrenal in 12%. Triplet combinations (i.e., VD plus a third agent) versus VD alone were associated with higher rates of renal responses (72 vs. 50%; P=0.06). Fifteen of the 31 (48%) patients became dialysis independent within a median of 217 days (range 11-724). Triplets were associated with a higher probability of dialysis discontinuation (57 vs. 35%). Serum free light chain (sFLC) level ≥11,550 mg/L was associated with lower rates of major renal response, longer time to major renal response, lower probability, and longer time to dialysis discontinuation. Rapid myeloma response (≥PR within the first month) was also associated with higher rates of renal response. Patients who became dialysis-independent had longer survival than those remaining on dialysis. In conclusion, VD-based triplets are associated with a significant probability of renal response and dialysis discontinuation, improving the survival of patients who became dialysis independent. Rapid disease response is important for renal recovery and sFLCs are predictive of the probability and of the time required for renal response. © 2016 Wiley Periodicals, Inc.

Renal failure (RF) is a common and severe complication of symptomatic myeloma, associated with significant morbidity and mortality. Such patients are commonly excluded from clinical trials. Bortezomib/dexamethasone (VD)-based regimens are the backbone of the treatment of newly diagnosed MM patients who present with severe RF even those requiring dialysis. We analyzed the outcomes of 83 consecutive bortezomib-treated patients with severe RF (eGFR<30 ml/min/1.73 m2), of which 31 (37%) required dialysis. By IMWG renal response criteria, 54 (65%) patients achieved at least MRrenal, including CRrenal in 35% and PRrenal in 12%. Triplet combinations (i.e., VD plus a third agent) versus VD alone were associated with higher rates of renal responses (72 vs. 50%; P=0.06). Fifteen of the 31 (48%) patients became dialysis independent within a median of 217 days (range 11-724). Triplets were associated with a higher probability of dialysis discontinuation (57 vs. 35%). Serum free light chain (sFLC) level ≥11,550 mg/L was associated with lower rates of major renal response, longer time to major renal response, lower probability, and longer time to dialysis discontinuation. Rapid myeloma response (≥PR within the first month) was also associated with higher rates of renal response. Patients who became dialysis-independent had longer survival than those remaining on dialysis. In conclusion, VD-based triplets are associated with a significant probability of renal response and dialysis discontinuation, improving the survival of patients who became dialysis independent. Rapid disease response is important for renal recovery and sFLCs are predictive of the probability and of the time required for renal response. © 2016 Wiley Periodicals, Inc.

This study focuses on botanical features gleaned from the literary source Hypnerotomachia Poliphili (1499); the analysis reveals that Hypnerotomachia Poliphili includes 285 botanical entities associated with 672 textual passages, which have not hitherto been reported. Roses, myrtle, pines, cypresses, laurel, acanthus, oaks, junipers, ivy, thyme, violets, sandalwoods and orange trees are the most frequently cited plants. Shrubs dominate with 43%, while herbs and trees follow with 28% and 26%, respectively. Arbutus, dittany, cypress, fig tree, labdanum, laurel, myrtle, oaks, oleander, wild and cultivated olive trees, oregano, pine, thyme, grapevines are associated with the diversity of Mediterranean ecosystems. In addition, numerous textual passages of Hypnerotomachia Poliphili mentioning flowering and fruiting plants reveal the seasonality of the Mediterranean region. Exotic plants, such as frankincense tree, myrrh, banana, pepper, sandalwood and jasmines are also included. Thorny plants, sharp thistles and cedars are cited in the text as occurring among ancient monuments and historical ruins. The botanical content of Hypnerotomachia Poliphili constitutes an alternate source of botanical observation, which includes historical, allegoric and symbolic information.

Transmembrane proteins translocate co-translationally in the endoplasmic reticulum (ER) membrane and traffic as vesicular cargoes, via the Golgi, in their final membrane destination. Misfolding in the ER leads to protein degradation basically through the ERAD/proteasome system. Here, we use a mutant version of the purine transporter UapA (ΔR481) to show that specific misfolded versions of plasma membrane cargoes undergo vacuolar turnover prior to localization in the plasma membrane. We show that non-endocytic vacuolar turnover of ΔR481 is dependent on BsdA(Bsd2) , an ER transmembrane adaptor of HulA(Rsp5) ubiquitin ligase. We obtain in vivo evidence that BsdA(Bsd2) interacts with HulA(Rsp5) and ΔR481, primarily in the ER. Importantly, accumulation of ΔR481 in the ER triggers delivery of the selective autophagy marker Atg8 in vacuoles along with ΔR481. Genetic block of autophagy (atg9Δ, rabO(ts) ) reduces, but does not abolish, sorting of ΔR481 in the vacuoles, suggesting that a fraction of the misfolded transporter might be redirected for vacuolar degradation via the Golgi. Our results support that multiple routes along the secretory pathway operate for the detoxification of Aspergillus nidulans cells from misfolded membrane proteins, and that BsdA is key factor for marking specific misfolded cargoes. This article is protected by copyright. All rights reserved.

Background: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m2 on days 1 and 2 of cycle 1; 56 mg/m2 thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m2; intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. Findings: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44-0·65]; p<0·0001). On-study death due to adverse events occurred in 18 (4%) of 464 patients in the carfilzomib group and in 16 (3%) of 465 patients in the bortezomib group. Serious adverse events were reported in 224 (48%) of 463 patients in the carfilzomib group and in 162 (36%) of 456 patients in the bortezomib group. The most frequent grade 3 or higher adverse events were anaemia (67 [14%] of 463 patients in the carfilzomib group vs 45 [10%] of 456 patients in the bortezomib group), hypertension (41 [9%] vs 12 [3%]), thrombocytopenia (39 [8%] vs 43 [9%]), and pneumonia (32 [7%] vs 36 [8%]). Interpretation: For patients with relapsed or refractory multiple myeloma, carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option. Funding: Onyx Pharmaceuticals, Inc., an Amgen subsidiary. © 2016 Elsevier Ltd.

Introduction: Carfilzomib, a second-generation proteasome inhibitor, has been increasingly used in relapsed/refractory multiple myeloma (MM) since its initial approval by the Food and Drug Administration in 2012, either as a single agent or in combination with other known anti-myeloma treatments. Based on its efficacy and safety profile in the relapsed/refractory setting, carfilzomib is currently evaluated in patients with de novo MM. Areas covered: Here, we will shed some light on the introduction of carfilzomib as an effective anti-myeloma treatment, presenting its mechanism of action, its response rates and adverse events, as well as a summary of all clinical trials evaluating current dosage and schedule of administration. We will follow the entire path of drug’s development from the bench of preclinical studies to the market and bedside delivery. Revising the published evidence, we will try to answer all questions raised about the novel drug, expressing in parallel our site experience. Expert opinion: Carfilzomib, alone or in combination with other agents, is a welcome therapeutic option for MM patients with a well-defined toxicity profile. Results of ongoing trials are expected in order to update drug indications and maximize its therapeutic benefits in patients with refractory/relapse MM. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Introduction: Carfilzomib, a second-generation proteasome inhibitor, has been increasingly used in relapsed/refractory multiple myeloma (MM) since its initial approval by the Food and Drug Administration in 2012, either as a single agent or in combination with other known anti-myeloma treatments. Based on its efficacy and safety profile in the relapsed/refractory setting, carfilzomib is currently evaluated in patients with de novo MM. Areas covered: Here, we will shed some light on the introduction of carfilzomib as an effective anti-myeloma treatment, presenting its mechanism of action, its response rates and adverse events, as well as a summary of all clinical trials evaluating current dosage and schedule of administration. We will follow the entire path of drug’s development from the bench of preclinical studies to the market and bedside delivery. Revising the published evidence, we will try to answer all questions raised about the novel drug, expressing in parallel our site experience. Expert opinion: Carfilzomib, alone or in combination with other agents, is a welcome therapeutic option for MM patients with a well-defined toxicity profile. Results of ongoing trials are expected in order to update drug indications and maximize its therapeutic benefits in patients with refractory/relapse MM. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n548; Rd, n552) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standardrisk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. Copyright © 2011 by the American Association for the Advancement of Science; all rights reserved.

The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n548; Rd, n552) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standardrisk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. Copyright © 2011 by the American Association for the Advancement of Science; all rights reserved.

© Athens Medical Society. In March 2013, the Health Procurement Committee of the Greek Ministry of Health appointed a committee consisting of laboratory scientists to compile a list of laboratory tests performed on biological fluids, cells and tissues. This committee compiled a list entitled Catalog of Uniform Nomenclature and Coding of Laboratory Tests (CUNCLT), using as its basis the list of reagents of the European Diagnostics Manufacturers Association (EDMA). The CUNCLT refers to the nomenclature of the laboratory tests and does not include all the materials (reagents, consumables, solutions, calibrators, controls, equipment, etc.) and software that may be necessary for performing the tests. The CUNCLT categorizes the laboratory tests that are performed on biological fluids, cells and tissues into eight main categories, each including subcategories of the 1st and 2nd levels. The eight main categories of the CUNCLT, namely Clinical Chemistry- Biochemistry, Immunochemistry, Hematology, Microbiology (cultures), Infectious Immunology, Molecular Biology and Genetics, Pathology-Cytology, Immunology, generally correspond to the categories of clinical laboratories that operate in public hospitals. The CUNCLT includes a total of 2,403 tests and according to its creation rationale, it is imperative that this list is regularly updated. CUNCLT is an important effort at the recording and classification of the laboratory tests carried out in clinical laboratories on biological fluids, cells and tissues. This list could be the basis for introducing the coding of laboratory tests in the laboratory information systems of public hospitals, for matching with the codes of laboratory tests prescribed by the National Organization for Health Care Services (EOPYY) and for specifications for the purchase of the reagents for laboratory testing.

Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder and bridges monoclonal gammo- pathyof undetermined significance to multiple myeloma (MM), based on higher levels of circulating monoclonal immunoglobulin and bone marrow plasmocytosis without end-organ damage. Until a Spanish study reported fewer MM-related events and better overall survival among patients with high- risk SMM treated with lenalidomide and dexamethasone, prior studies had failed to show improved survival with earlier intervention,although a reduction in skeletal-related events (without any impact on disease progression) has been described with bisphosphonate use. Risk factors have now been defined, and a subset of ultra-high-risk patients have been reclassified by the International Myeloma Working Group as MM, and thus will require optimal MM treatment, based on biomarkers that identify patients with a >80% risk of progression. The number of these redefined patients is small (~10%), but important to unravel, because theirriskof progression to overt MM is substantial ($80% within 2 years). Patients with a high-risk cytogenetic profile are not yet considered for early treatment, because groups are heterogeneous and risk factors other than cytogenetics are deemed to weight higher. Because patients with ultra-high- risk SMM are now considered as MM and may be treated as such, concerns exist that earlier therapy may increase the risk of selecting resistant clones and induce side effects and costs. Therefore, an even more accurate identification of patients who would benefit from interventions needs to be performed, and clinical judgment and careful discussion of pros and cons of treatment initiation need to be undertaken. For the majority of SMM patients, the standard of care remains observation until development of symptomatic MM occurs, encouraging participation in ongoing and upcoming SMM/early MM clinical trials, as well as consideration of bisphosphonate use in patients with early bone loss. © AlphaMed Press 2016.

Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder and bridges monoclonal gammo- pathyof undetermined significance to multiple myeloma (MM), based on higher levels of circulating monoclonal immunoglobulin and bone marrow plasmocytosis without end-organ damage. Until a Spanish study reported fewer MM-related events and better overall survival among patients with high- risk SMM treated with lenalidomide and dexamethasone, prior studies had failed to show improved survival with earlier intervention,although a reduction in skeletal-related events (without any impact on disease progression) has been described with bisphosphonate use. Risk factors have now been defined, and a subset of ultra-high-risk patients have been reclassified by the International Myeloma Working Group as MM, and thus will require optimal MM treatment, based on biomarkers that identify patients with a >80% risk of progression. The number of these redefined patients is small (~10%), but important to unravel, because theirriskof progression to overt MM is substantial ($80% within 2 years). Patients with a high-risk cytogenetic profile are not yet considered for early treatment, because groups are heterogeneous and risk factors other than cytogenetics are deemed to weight higher. Because patients with ultra-high- risk SMM are now considered as MM and may be treated as such, concerns exist that earlier therapy may increase the risk of selecting resistant clones and induce side effects and costs. Therefore, an even more accurate identification of patients who would benefit from interventions needs to be performed, and clinical judgment and careful discussion of pros and cons of treatment initiation need to be undertaken. For the majority of SMM patients, the standard of care remains observation until development of symptomatic MM occurs, encouraging participation in ongoing and upcoming SMM/early MM clinical trials, as well as consideration of bisphosphonate use in patients with early bone loss. © AlphaMed Press 2016.

INTRODUCTION: The Ciliary Neurotrophic Factor (CNTF) is a pluripotent cytokine with anorexigenic actions in the hypothalamus that improves insulin sensitivity, increases energy expenditure and induces weight loss. Since CNTF also has an established myotrophic role, we sought to examine whether skeletal muscle contributes to the CNTF-induced metabolic improvement and identify the molecular mechanisms mediating these effects. METHODS: We used a mouse model of diet-induced obesity, to which high or low CNTF doses were administered for 7days. Whole transcriptome expression levels were analyzed in dissected soleus muscles using microarrays and data were then confirmed using qRT-PCR. RESULTS: We demonstrate that CNTF administration significantly downregulates leptin, while it upregulates follistatin and Pak1; a molecule associated with insulin sensitization in skeletal muscle. A significant overexpression of muscle differentiation related genes and downregulation of established atrophy mediators was observed. CONCLUSIONS: The overall gene expression changes suggest an indirect, beneficial effect of CNTF on metabolism, energy expenditure and insulin sensitivity, exerted by the pronounced stimulation of muscle growth, with similarities to the described effect of follistatin and the activation of the Akt pathway in skeletal muscle.

CONTEXT: Resistin is associated with inflammation, atherosclerosis and cardiovascular (CV) disease. OBJECTIVE: To associate circulating resistin with all-cause and CV mortality in chronic kidney disease (CKD) patients. METHODS: Serum resistin was determined in a cohort of 80 elderly, non-diabetic patients with stable CKD at different stages in a follow-up period of 5 years. RESULTS: Circulating resistin was significantly elevated in deceased compared to alive patients. Resistin emerged as an independent biomarker of all-cause and CV mortality after a 5-year follow-up period. CONCLUSION: Elevated circulating resistin was a significant independent predictor of CV and all-cause mortality in elderly, non-diabetic CKD patients

CONTEXT: Resistin is associated with inflammation, atherosclerosis and cardiovascular (CV) disease. OBJECTIVE: To associate circulating resistin with all-cause and CV mortality in chronic kidney disease (CKD) patients. METHODS: Serum resistin was determined in a cohort of 80 elderly, non-diabetic patients with stable CKD at different stages in a follow-up period of 5 years. RESULTS: Circulating resistin was significantly elevated in deceased compared to alive patients. Resistin emerged as an independent biomarker of all-cause and CV mortality after a 5-year follow-up period. CONCLUSION: Elevated circulating resistin was a significant independent predictor of CV and all-cause mortality in elderly, non-diabetic CKD patients.

Climate change is expected to affect the hydrological cycle, altering seawater level and groundwater recharge to coastal aquifers with various other associated impacts on natural ecosystems and human activities. As the sustainable use of groundwater resources is a great challenge for many countries in the world, groundwater modeling has become a very useful and well established tool for studying groundwater management problems. This study investigates the impacts of climate change on the groundwater of the deltaic plain of River Pinios (Central Greece). Geophysical data processing indicates that the phreatic aquifer extends mainly in the central and northern parts of the region. A one-layer transient groundwater flow and contaminant mass transport model of the aquifer system is calibrated and validated. Impacts of climate change were evaluated by incorporating the estimated recharge input and sea level change of different future scenarios within the simulation models. The most noticeable and consistent result of the climate change impact simulations is a prominent sea water intrusion in the coastal aquifer mainly as a result of sea level change which underlines the need for a more effective planning of environmental measures.

We provide new evidence on sea surface temperature (SST) variations and paleoceanographic/paleoenvironmental changes over the past 1500 years for the north Aegean Sea (NE Mediterranean). The reconstructions are based on multiproxy analyses, obtained from the high resolution (decadal to multi-decadal) marine record M2 retrieved from the Athos basin. Reconstructed SSTs show an increase from ca. 850 to 950 AD and from ca. 1100 to 1300 AD. A cooling phase of almost 1.5 °C is observed from ca. 1600 AD to 1700 AD. This seems to have been the starting point of a continuous SST warming trend until the end of the reconstructed period, interrupted by two prominent cooling events at 1832 ± 15 AD and 1995 ± 1 AD. Application of an adaptive Kernel smoothing suggests that the current warming in the reconstructed SSTs of the north Aegean might be unprecedented in the context of the past 1500 years. Internal variability in atmospheric/oceanic circulations systems as well as external forcing as solar radiation and volcanic activity could have affected temperature variations in the north Aegean Sea over the past 1500 years. The marked temperature drop of approximately ∼2 °C at 1832 ± 15 yr AD could be related to the 1809 ΑD ‘unknown’ and the 1815 AD Tambora volcanic eruptions. Paleoenvironmental proxy-indices of the M2 record show enhanced riverine/continental inputs in the northern Aegean after ca. 1450 AD.The paleoclimatic evidence derived from the M2 record is combined with a socio-environmental study of the history of the north Aegean region. We show that the cultivation of temperature-sensitive crops, i.e. walnut, vine and olive, co-occurred with stable and warmer temperatures, while its end coincided with a significant episode of cooler temperatures. Periods of agricultural growth in Macedonia coincide with periods of warmer and more stable SSTs, but further exploration is required in order to identify the causal links behind the observed phenomena. The Black Death likely caused major changes in agricultural activity in the north Aegean region, as reflected in the pollen data from land sites of Macedonia and the M2 proxy-reconstructions. Finally, we conclude that the early modern peaks in mountain vegetation in the Rhodope and Macedonia highlands, visible also in the M2 record, were very likely climate-driven.

AbstractWe provide new evidence on sea surface temperature (SST) variations and paleoceanographic/paleoenvironmental changes over the past 1500 years for the north Aegean Sea (NE Mediterranean). The reconstructions are based on multiproxy analyses, obtained from the high resolution (decadal to multi-decadal) marine record M2 retrieved from the Athos basin. Reconstructed SSTs show an increase from ca. 850 to 950 AD and from ca. 1100 to 1300 AD. A cooling phase of almost 1.5 °C is observed from ca. 1600 AD to 1700 AD. This seems to have been the starting point of a continuous SST warming trend until the end of the reconstructed period, interrupted by two prominent cooling events at 1832 ± 15 AD and 1995 ± 1 AD. Application of an adaptive Kernel smoothing suggests that the current warming in the reconstructed SSTs of the north Aegean might be unprecedented in the context of the past 1500 years. Internal variability in atmospheric/oceanic circulations systems as well as external forcing as solar radiation and volcanic activity could have affected temperature variations in the north Aegean Sea over the past 1500 years. The marked temperature drop of approximately ∼2 °C at 1832 ± 15 yr AD could be related to the 1809 ΑD ‘unknown’ and the 1815 AD Tambora volcanic eruptions. Paleoenvironmental proxy-indices of the M2 record show enhanced riverine/continental inputs in the northern Aegean after ca. 1450 AD. The paleoclimatic evidence derived from the M2 record is combined with a socio-environmental study of the history of the north Aegean region. We show that the cultivation of temperature-sensitive crops, i.e. walnut, vine and olive, co-occurred with stable and warmer temperatures, while its end coincided with a significant episode of cooler temperatures. Periods of agricultural growth in Macedonia coincide with periods of warmer and more stable SSTs, but further exploration is required in order to identify the causal links behind the observed phenomena. The Black Death likely caused major changes in agricultural activity in the north Aegean region, as reflected in the pollen data from land sites of Macedonia and the M2 proxy-reconstructions. Finally, we conclude that the early modern peaks in mountain vegetation in the Rhodope and Macedonia highlands, visible also in the M2 record, were very likely climate-driven.

{This study shed light on the long term air temperature changes in the troposphere over the Mediterranean. For this purpose, we utilized the radiosonde datasets for the barometric levels at 850, 700, 500, 300, 200, 150, and 100 hPa from seventeen meteorological stations within the Mediterranean, for the period 1965-2015. Besides, the gridded reanalysis products of upper air temperature for the respective barometric pressure levels from the European Centre for Medium-Range Weather Forecasts (ECMWF, ERA-Interim) and the National Center for Environmental Prediction-National Center for Atmospheric Research (NCEPNCAR) were used and compared to stations' datasets. We analyzed the trends and variability of upper air temperature on seasonal and annual basis. The impact of atmospheric circulation, by means of specific climatic indices such as Mediterranean Oscillation Index (MOI), North Sea Caspian Pattern Index (NCPI) and North Atlantic Oscillation Index (NAOI), was also examined. The results of our analysis indicate the anthropogenic forcing to climate variability, especially in lower/middle troposphere against upper troposphere over the Mediterranean.}

Cardiac dysfunction determines prognosis in amyloid light-chain (AL) amyloidosis. The heart is the central organ of the vascular system in which endothelium function is critical for the circulatory homeostasis, but there are limited data on endothelial function in AL amyloidosis. von Willebrand factor (VWF) has been considered as a marker of endothelial activation and dysfunction, whereas a disintegrin and metalloproteinase with thrombospondin type-1 repeats 13 (ADAMTS-13) cleaves VWF multimers, but both have been associated with prognosis in cardiovascular disease. We measured the serum levels of VWF (VWF:Ag) and ADAMTS-13 antigens in 111 newly diagnosed patients with AL amyloidosis. The levels of VWF:Ag were significantly higher than in healthy controls; 76% of patients with AL had VWF:Ag levels higher than the upper levels of controls. There was no significant association of VWF:Ag levels with patterns of organ involvement, free light-chain levels, the levels of cardiac biomarkers, or renal dysfunction but correlated with low systolic blood pressure. VWF:Ag levels ≥230.0 U/dL were associated with higher probability of early death and poor survival independently of cardiac biomarkers and low systolic blood pressure (SBP). Moreover, among patients with Mayo stage III or stage IIIB (that is stage III with N-terminal pro-brain natriuretic peptide [NTproBNP] >8500 pg/mL) disease, VWF:Ag identified subgroups of patients with very poor outcome. Low ADAMTS-13 levels correlated with high levels of NTproBNP but had no independent prognostic significance. In conclusion, high VWF:Ag levels, probably representing endothelial dysfunction, are associated with prognosis in patients with AL amyloidosis, independently of other features of the disease or cardiac biomarkers. © 2016 by The American Society of Hematology.

Cardiac dysfunction determines prognosis in amyloid light-chain (AL) amyloidosis. The heart is the central organ of the vascular system in which endothelium function is critical for the circulatory homeostasis, but there are limited data on endothelial function in AL amyloidosis. von Willebrand factor (VWF) has been considered as a marker of endothelial activation and dysfunction, whereas a disintegrin and metalloproteinase with thrombospondin type-1 repeats 13 (ADAMTS-13) cleaves VWF multimers, but both have been associated with prognosis in cardiovascular disease. We measured the serum levels of VWF (VWF:Ag) and ADAMTS-13 antigens in 111 newly diagnosed patients with AL amyloidosis. The levels of VWF:Ag were significantly higher than in healthy controls; 76% of patients with AL had VWF:Ag levels higher than the upper levels of controls. There was no significant association of VWF:Ag levels with patterns of organ involvement, free light-chain levels, the levels of cardiac biomarkers, or renal dysfunction but correlated with low systolic blood pressure. VWF:Ag levels ≥230.0 U/dL were associated with higher probability of early death and poor survival independently of cardiac biomarkers and low systolic blood pressure (SBP). Moreover, among patients with Mayo stage III or stage IIIB (that is stage III with N-terminal pro-brain natriuretic peptide [NTproBNP] >8500 pg/mL) disease, VWF:Ag identified subgroups of patients with very poor outcome. Low ADAMTS-13 levels correlated with high levels of NTproBNP but had no independent prognostic significance. In conclusion, high VWF:Ag levels, probably representing endothelial dysfunction, are associated with prognosis in patients with AL amyloidosis, independently of other features of the disease or cardiac biomarkers. © 2016 by The American Society of Hematology.

BACKGROUND: Advanced glycation end products (AGEs) and their receptor RAGE emerge as important pathogenic contributors in colorectal carcinogenesis. However, their relationship to the detoxification enzyme Glyoxalase (GLO)-I and Adiponectin receptors (AdipoR1, AdipoR2) in colorectal carcinoma (CRC) is currently understudied. In the present study, we investigated the expression levels of the above molecules in CRC compared to adjacent non-tumoral tissue and their potential correlation with clinicopathological characteristics and patients' survival. METHODS: We analyzed the immunohistochemical expression of AGE, RAGE, GLO-1, AdipoR1 and AdipoR2 in 133 primary CRC cases, focusing on GLO-I. The tumour MSI status was further assessed in mucinous carcinomas. Western immunoblotting was employed for validation of immunohistochemical data in normal and tumoral tissues as well in three CRC cell lines. An independent set of 55 patients was also used to validate the results of univariate survival analysis regarding GLO-I. RESULTS: CRC tissue showed higher intensity of both AGE and RAGE expression compared with normal colonic mucosa which was negative for GLO-I in most cases (78 %). Western immunoblotting confirmed AGE, RAGE and GLO-I overexpression in tumoral tissue. GLO-I expression was directly related to RAGE and inversely related to AGE immunolabeling. There was a trend towards higher expression of all markers (except for RAGE) in the subgroup of mucinous carcinomas which, although of borderline significance, seemed to be more prominent for AdipoR1 and AGE. Additionally, AGE, AdipoR1 and Adipo R2 expression was related to tumor grade, whereas GLO-1 and AdipoR1 to T-category. In survival analysis, AdipoR2 and GLO-I overexpression predicted shortened survival in the entire cohort and in early stage cases, an effect which for GLO-I was reproduced in the validation cohort. Moreover, GLO-I emerged as an independent prognosticator of adverse significance in the patients' cohort. CONCLUSIONS: We herein provide novel evidence regarding the possible interactions between the components of AGE-RAGE axis, GLO-I and adiponectin receptors in CRC. AGE and AdipoR1 are possibly involved in colorectal carcinogenesis, whereas AdipoR2 and GLO-I emerged as novel independent prognostic biomarkers of adverse significance for patients with early disease stage. Further studies are warranted to extend our observations and investigate their potential therapeutic significance.

Hu-antigen R (HuR) is considered to play a crucial role in tumor formation and growth by binding to mRNAs encoding proteins such as Cyclooxygenase-2 (COX-2) and inducing their expression via mRNA stabilization and/or altered translation. The present study aimed to evaluate the clinical significance of HuR and COX-2 proteins’ expression in human benign and malignant thyroid lesions. HuR and COX-2 proteins’ expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 98 patients with benign (n = 48) and malignant (n = 50) lesions and was statistically analyzed with clinicopathological parameters, follicular cells’ proliferative capacity and recurrence risk rate. Enhanced HuR and COX-2 expression was significantly more frequently observed in malignant compared to benign thyroid lesions (p = 0.0073 and p = 0.0016, respectively), as well as in papillary carcinomas compared to hyperplastic nodules (p = 0.0039 and p = 0.0009, respectively). Positive associations of both HuR and COX-2 expression with follicular cells’ proliferation rate were also noted (p = 0.0087 and p = 0.0127, respectively). In malignant thyroid lesions, elevated COX-2 expression was significantly associated with female patients’ gender (p = 0.0381) and the presence of lymph node metastases (p = 0.0296). The present data support evidence that both HuR and COX-2 may be involved in the malignant state of thyroid neoplasia and may be utilized in the diagnosis of malignant thyroid tumors.

BACKGROUND: European guidelines recommend treatment of chronic hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study was performed to gain insight in prevalence and characteristics of NA resistance in Europe. METHODS: A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum hepatitis B virus DNA in European tertiary referral centers. RESULTS: Data from 1568 patients were included. The majority (73.8%) were exposed to lamivudine monotherapy. Drug-resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n = 102), full resistance was present in 35.3%. Independent risk factors for resistance were age, viral load, and lamivudine exposure (P < .001). CONCLUSIONS: These findings support resistance testing in cases of apparent NA therapy failure. This survey highlights the impact of exposure to lamivudine and adefovir on development of drug resistance and cross-resistance. Continued use of these NAs needs to be reconsidered at a pan-European level.

{In the present study, the dynamical downscaling technique was applied in the Advanced Weather Research and Forecasting numerical model WRF-ARW, to investigate and validate the performance of different physics parameterizations. The WRF model, was forced by ERA-INTERIM reanalysis data, for a short period of one year (January 2002-December 2002), over the area of the MED-CORDEX domain of 20 km horizontal resolution, downscaled to the domain of Greece with grid spacing of 5 km. Simulations with the Yonsei University (YSU) and Mellor-Yamada- Janjic (MYJ) schemes for boundary layer parameterizations were chosen, along with the corresponding surface layer schemes, as well as, cumulus physics schemes of Kain-Fitsch and Grell-Devenyi. The results of the model simulations have been compared with all available station measurements from the European Climate Assessment and Dataset (ECA&D) for the daily precipitation and 2-m air temperature, through the computation of statistical metrics. The study led to a more reliable choice of physics configurations schemes for the WRF model, in order to simulate future climate model experiments to assess the impact of climate change over the domain of interest.}

Purpose of investigation: To describe a novel approach for longitudinal vaginal septum (LVS) resection. Materials and Methods: Two cases of young girls with a uterus didelphys and a longitudinal vaginal septum. The technique consisted in grasping the vaginal septum with a laparoscopic 33-cm long bipolar cutting forceps, five-mm in diameter, and divided it to its midportion towards the two cervices. Results: In both cases, the procedure was straightforward, uncomplicated, completed within three minutes and the patients were discharged four hours later. It was associated with minimal blood loss, short recovery time, absence of local ischemia, and optimum healing process. Conclusion: The authors believe that surgical safety, efficacy and operative result make bipolar cutting forceps a tailored option for LVS resection.

A range of iron(II) complexes incorporating the silylated pentalene ligands (Pn†H = 1,4-{SiiPr3}2C8H5and Pn† = 1,4-{SiiPr3}2C8H4) have been investigated as model molecules/building blocks for metallocene-based polymers. Six complexes have been synthesised and extensively characterised by a range of techniques, including by cyclic voltammetry and X-ray diffraction studies. Amongst these compounds are the homobimetallic [Cp∗Fe]2(μ-Pn†) which is a fused analogue of biferrocene, and the 3d/4s heterobimetallic [Cp∗Fe(η5-Pn†)][K] which forms an organometallic polymer in the solid state. DFT calculations on model mono-Fe(η5-Pn) compounds reveal the charge densities on the uncoordinated carbon atoms of the pentalene ligand, and hence the potential for incorporating these units into heteronuclear bimetallic complexes is assessed.

INTRODUCTION: Peritoneal Encapsulation (PE) is a scarce congenital malformation, characterized by a supplementary peritoneal membrane that covers all or a part of the small intestine. PRESENTATION OF CASE: PE was unexpectantly discovered in a young woman during laparotomy for bowel obstruction. There were no specific pre-operative indications of this malformation. The operation was uneventful. DISCUSSION: PE is a very rare congenital anatomical anomaly that is difficultly identified pre-operatively. PE is mainly asymptomatic, but in some cases, like in the presented one, PE presents with small bowel obstruction. Surgeons should be aware of this malformation and suspect it when encountering a patient with small bowel obstruction without other etiological factors. CONCLUSION: Knowledge of this peculiar congenital anomaly is pivotal, so that accurate diagnosis and appropriate management of it are direct and efficient.

Hadronic models of blazar emission constitute an interesting alternative to the more popular leptonic ones. Using the BL Lac object Mrk 421 as a characteristic example, we present two distinct ways of modeling the spectral energy distribution of blazars in the hadronic context, and we discuss the predictions of each variant on the spectral shape, the multi-wavelength variability, the cosmic-ray flux, and the high-energy neutrino emission. Focusing on the latter, we then present an application of the hadronic model to individual BL Lacs that were recently suggested to be the counterparts of some of the IceCube neutrinos.

Endogenous retroviruses (ERVs) comprise 6-8% of the human genome. HERVs are silenced in most normal tissues, up-regulated in stem cells and in placenta but also in cancer and HIV-1 infection. Crucially, there are conflicting reports on detecting HERV RNA in non-cellular clinical samples such as plasma that suggest the study of HERV RNA can be daunting. Indeed, we find that the use of real-time PCR in a quality assured clinical laboratory setting can be sensitive to low-level proviral contamination. We developed a mathematical model for low-level contamination that allowed us to design a laboratory protocol and standard operating procedures for robust measurement of HERV RNA. We focus on one family, HERV-K HML-2 (HK2) that has been most recently active even though they invaded our ancestral genomes almost 30 millions ago. We extensively validated our experimental design on a model cell culture system showing high sensitivity and specificity, totally eliminating the proviral contamination. We then tested 236 plasma samples from patients infected with HIV-1, HCV or HBV and found them to be negative. The study of HERV RNA for human translational studies should be performed with extensively validated protocols and standard operating procedures to control the widespread low-level human DNA contamination.

List of contributions from the Cherenkov Telescope Array (CTA) Consortium presented at the 6th International Symposium on High-Energy Gamma-Ray Astronomy (Gamma 2016), July 11-15, 2016, in Heidelberg, Germany.

In this paper we propose and test a methodology for constructing a credit rating model. We follow a polytomous ordered probit analysis leading to the specification of statistically significant credit rating intervals. We test our model with accounting data of Greek listed firms over the years 2004–2013, a period which includes both the pre-crisis growth and the crisis phase of the Greek economy and the stock market. Using the empirically—based rating categories that the model generates endogenously, we observe not only a clear and timely response of ratings to the changing economic environment, but we also obtain significant predictive ability over a period of one, two and three years.

In this paper we propose and test a methodology for constructing a credit rating model. We follow a polytomous ordered probit analysis leading to the specification of statistically significant credit rating intervals. We test our model with accounting data of Greek listed firms over the years 2004–2013, a period which includes both the pre-crisis growth and the crisis phase of the Greek economy and the stock market. Using the empirically—based rating categories that the model generates endogenously, we observe not only a clear and timely response of ratings to the changing economic environment, but we also obtain significant predictive ability over a period of one, two and three years.

Mitochondria are highly dynamic organelles that provide essential metabolic functions and represent the major bioenergetic hub of eukaryotic cell. Therefore, maintenance of mitochondria activity is necessary for the proper cellular function and survival. To this end, several mechanisms that act at different levels and time points have been developed to ensure mitochondria quality control. An interconnected highly integrated system of mitochondrial and cytosolic chaperones and proteases along with the fission/fusion machinery represents the surveillance scaffold of mitostasis. Moreover, nonreversible mitochondrial damage targets the organelle to a specific autophagic removal, namely, mitophagy. Beyond the organelle dynamics, the constant interaction with the ubiquitin-proteasome-system (UPS) has become an emerging aspect of healthy mitochondria. Dysfunction of mitochondria and UPS increases with age and correlates with many age-related diseases including cancer and neurodegeneration. In this review, we discuss the functional cross talk of proteostasis and mitostasis in cellular homeodynamics and the impairment of mitochondrial quality control during ageing, cancer, and neurodegeneration.

Waldenstrom's macroglobulinaemia (WM) is a B-cell neoplasm in which bone marrow is infiltrated by lymphoplasmacytic cells that secrete monoclonal immunoglobulin M (IgM). More than a decade ago, specific criteria were agreed to define diagnosis and symptomatic disease requiring therapy; however, treatment recommendations change as new options emerge. Treatment decisions consider specific disease characteristics (burden of disease, IgM levels, presence of cytopenias) and patient characteristics (age, comorbidities, toxicity). Recently, the impact of specific mutations (in MYD88 and CXCR4) in response to specific therapies has been reported, and this may affect treatment decisions in the future. Chemo-immunotherapy combinations based on rituximab with cyclophosphamide/dexamethasone, bendamustine or bortezomib/dexamethasone are indicated for most patients. The BTK inhibitor ibrutinib was recently approved for patients with WM, and is a new option for selected newly diagnosed or relapsing patients. New B-cell receptor inhibitors, second-generation proteasome inhibitors and mammalian target of rapamycin inhibitors are promising; however, more data are needed from high-quality clinical trials. © 2016 Elsevier Ltd

Waldenstrom's macroglobulinaemia (WM) is a B-cell neoplasm in which bone marrow is infiltrated by lymphoplasmacytic cells that secrete monoclonal immunoglobulin M (IgM). More than a decade ago, specific criteria were agreed to define diagnosis and symptomatic disease requiring therapy; however, treatment recommendations change as new options emerge. Treatment decisions consider specific disease characteristics (burden of disease, IgM levels, presence of cytopenias) and patient characteristics (age, comorbidities, toxicity). Recently, the impact of specific mutations (in MYD88 and CXCR4) in response to specific therapies has been reported, and this may affect treatment decisions in the future. Chemo-immunotherapy combinations based on rituximab with cyclophosphamide/dexamethasone, bendamustine or bortezomib/dexamethasone are indicated for most patients. The BTK inhibitor ibrutinib was recently approved for patients with WM, and is a new option for selected newly diagnosed or relapsing patients. New B-cell receptor inhibitors, second-generation proteasome inhibitors and mammalian target of rapamycin inhibitors are promising; however, more data are needed from high-quality clinical trials. © 2016 Elsevier Ltd

Introduction: Renal impairment (RI) is one of the most common complication of multiple myeloma (MM). RI is present in almost 20% of MM patients at diagnosis and in 40%-50% of patients during the course of their disease. Areas covered: Biology along with tools for diagnosis and management of RI are reported in this paper. Papers published in PubMed and reported abstracts up to May 2016 were used. Expert opinion: Moderate and severe RI increases the risk of early death; thus rapid intervention and initiation of anti-myeloma treatment is essential and improves renal outcomes in RI patients. Bortezomib and dexamethasone triplet combinations are the current standard of therapy for MM patients with acute kidney injury due to cast nephropathy; they offer high rates of both anti-myeloma response and renal recovery. Thalidomide and lenalidomide may be used in bortezomib refractory patients. In the relapsed/refractory setting additional treatment options such as carfilzomib, pomalidomide and monoclonal antibodies are available; however, there is limited data for their effects on patients with RI. High dose melphalan with autologous stem cell transplantation should be considered in otherwise eligible patients with RI. Finally, high cut-off hemodialysis membranes do not seem to offer significant additive effects on anti-myeloma therapies. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Introduction: Renal impairment (RI) is one of the most common complication of multiple myeloma (MM). RI is present in almost 20% of MM patients at diagnosis and in 40%-50% of patients during the course of their disease. Areas covered: Biology along with tools for diagnosis and management of RI are reported in this paper. Papers published in PubMed and reported abstracts up to May 2016 were used. Expert opinion: Moderate and severe RI increases the risk of early death; thus rapid intervention and initiation of anti-myeloma treatment is essential and improves renal outcomes in RI patients. Bortezomib and dexamethasone triplet combinations are the current standard of therapy for MM patients with acute kidney injury due to cast nephropathy; they offer high rates of both anti-myeloma response and renal recovery. Thalidomide and lenalidomide may be used in bortezomib refractory patients. In the relapsed/refractory setting additional treatment options such as carfilzomib, pomalidomide and monoclonal antibodies are available; however, there is limited data for their effects on patients with RI. High dose melphalan with autologous stem cell transplantation should be considered in otherwise eligible patients with RI. Finally, high cut-off hemodialysis membranes do not seem to offer significant additive effects on anti-myeloma therapies. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

We consider the problem of customer equilibrium strategies in an M/M/1 queue under dynamic service control. The service rate switches between a low and a high value depending on system congestion. Arriving customers do not observe the system state at the moment of arrival. We show that due to service rate variation, the customer equilibrium strategy is not generally unique, and derive an upper bound on the number of possible equilibria. For the problem of social welfare optimization, we numerically analyze the relationship between the optimal and equilibrium arrival rates as a function of various parameter values, and assess the level of inefficiency via the price of anarchy measure. We finally derive analytic solutions for the special case where the service rate switch occurs when the queue ceases to be empty. © 2016 Elsevier B.V. All rights reserved.

Background A variety of clinical and laboratory prognostic factors for multiple myeloma (MM) have been addressed in published studies. The prognostic significance of cytogenetic abnormalities is also under investigation. Patients and Methods The present study evaluated the potential prognostic role of cytogenetic events and their combinations in terms of overall survival in a large cohort of unselected patients with MM (n = 432). Multivariate Cox regression analysis was performed, adjusting for age, gender, Chronic Kidney Disease Epidemiology Collaboration Kidney Disease: Improving Global Outcomes classification, International Staging System score, Eastern Cooperative Oncology Group performance status, serum lactate dehydrogenase, serum calcium, platelet count, and blood hemoglobin. Results The presence of del(13q) (adjusted hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.18-2.47), t(4;14) (adjusted HR, 2.00; 95% CI, 1.19-3.35), and/or del(17p) (adjusted HR, 2.03; 95% CI, 1.22-3.37) was independently associated with poorer overall survival. The poor prognosis seemed more pronounced among patients harboring combinations of 2 adverse cytogenetic abnormalities. In contrast, t(14;16), t(11;14), and add(1q21) were not associated with overall survival. The effect of bortezomib seemed rather minimal in the modification of the prognostic role mediated by del(17p). Conclusion The presence of del(13q), t(4;14), and del(17p), singly or in combination, seems to be an independent poor prognostic factor for patients with MM. © 2016 Elsevier Inc.

Background A variety of clinical and laboratory prognostic factors for multiple myeloma (MM) have been addressed in published studies. The prognostic significance of cytogenetic abnormalities is also under investigation. Patients and Methods The present study evaluated the potential prognostic role of cytogenetic events and their combinations in terms of overall survival in a large cohort of unselected patients with MM (n = 432). Multivariate Cox regression analysis was performed, adjusting for age, gender, Chronic Kidney Disease Epidemiology Collaboration Kidney Disease: Improving Global Outcomes classification, International Staging System score, Eastern Cooperative Oncology Group performance status, serum lactate dehydrogenase, serum calcium, platelet count, and blood hemoglobin. Results The presence of del(13q) (adjusted hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.18-2.47), t(4;14) (adjusted HR, 2.00; 95% CI, 1.19-3.35), and/or del(17p) (adjusted HR, 2.03; 95% CI, 1.22-3.37) was independently associated with poorer overall survival. The poor prognosis seemed more pronounced among patients harboring combinations of 2 adverse cytogenetic abnormalities. In contrast, t(14;16), t(11;14), and add(1q21) were not associated with overall survival. The effect of bortezomib seemed rather minimal in the modification of the prognostic role mediated by del(17p). Conclusion The presence of del(13q), t(4;14), and del(17p), singly or in combination, seems to be an independent poor prognostic factor for patients with MM. © 2016 Elsevier Inc.

Background/Aim: Peripheral blood mononuclear cells (PBMCs) activated with immobilized monoclonal antibody against cluster of differentiation 3 (CD3) secrete cytokines in their culture supernatant (termed ACD3S). We examined the antitumor efficacy of ACD3S-activated NK-92 cells in vitro and in vivo. Materials and Methods: Interleukin (IL) 2-depleted NK-92 cells were reactivated with ACD3S, analyzed for their phenotype and tested for cytotoxicity, and perforin and interferon (IFN) production. Severe combined immunodeficient (SCID) mice xenografted with human melanoma and breast cancer cells were treated with ACD3S-activated NK-92 cells and tumor growth was monitored. Results: Brief activation of IL2-depleted NK-92 cells with ACD3S fully restored their in vitro cytotoxicity towards tumor cells. ACD3S-activated NK-92 cells were phenotypically similar to standard NK-92 cells, but exhibited prolonged cytotoxicity and produced higher levels of IFN. When adoptively transferred to tumor-bearing SCID mice, these cells retarded the growth of melanoma and breast tumors. Conclusion: Stimulation of NK-92 cells with ACD3S may be useful in clinical cancer therapy, as an alternative method for ex vivo natural killer cell activation.

BACKGROUND: Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival. RESULTS: At a median follow-up of 13.5 months in a protocol-specified interim analysis, 169 events of disease progression or death were observed (in 53 of 286 patients [18.5%] in the daratumumab group vs. 116 of 283 [41.0%] in the control group; hazard ratio, 0.37; 95% confidence interval [CI], 0.27 to 0.52; P<0.001 by stratified log-rank test). The Kaplan- Meier rate of progression-free survival at 12 months was 83.2% (95% CI, 78.3 to 87.2) in the daratumumab group, as compared with 60.1% (95% CI, 54.0 to 65.7) in the control group. A significantly higher rate of overall response was observed in the daratumumab group than in the control group (92.9% vs. 76.4%, P<0.001), as was a higher rate of complete response or better (43.1% vs. 19.2%, P<0.001). In the daratumumab group, 22.4% of the patients had results below the threshold for minimal residual disease (1 tumor cell per 105 white cells), as compared with 4.6% of those in the control group (P<0.001); results below the threshold for minimal residual disease were associated with improved outcomes. The most common adverse events of grade 3 or 4 during treatment were neutropenia (in 51.9% of the patients in the daratumumab group vs. 37.0% of those in the control group), thrombocytopenia (in 12.7% vs. 13.5%), and anemia (in 12.4% vs. 19.6%). Daratumumab-associated infusion-related reactions occurred in 47.7% of the patients and were mostly of grade 1 or 2. CONCLUSIONS: The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened progression-free survival among patients with relapsed or refractory multiple myeloma. Daratumumab was associated with infusion-related reactions and a higher rate of neutropenia than the control therapy. Copyright © 2016 Massachusetts Medical Society. All rights reserved.

BACKGROUND: Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival. RESULTS: At a median follow-up of 13.5 months in a protocol-specified interim analysis, 169 events of disease progression or death were observed (in 53 of 286 patients [18.5%] in the daratumumab group vs. 116 of 283 [41.0%] in the control group; hazard ratio, 0.37; 95% confidence interval [CI], 0.27 to 0.52; P<0.001 by stratified log-rank test). The Kaplan- Meier rate of progression-free survival at 12 months was 83.2% (95% CI, 78.3 to 87.2) in the daratumumab group, as compared with 60.1% (95% CI, 54.0 to 65.7) in the control group. A significantly higher rate of overall response was observed in the daratumumab group than in the control group (92.9% vs. 76.4%, P<0.001), as was a higher rate of complete response or better (43.1% vs. 19.2%, P<0.001). In the daratumumab group, 22.4% of the patients had results below the threshold for minimal residual disease (1 tumor cell per 105 white cells), as compared with 4.6% of those in the control group (P<0.001); results below the threshold for minimal residual disease were associated with improved outcomes. The most common adverse events of grade 3 or 4 during treatment were neutropenia (in 51.9% of the patients in the daratumumab group vs. 37.0% of those in the control group), thrombocytopenia (in 12.7% vs. 13.5%), and anemia (in 12.4% vs. 19.6%). Daratumumab-associated infusion-related reactions occurred in 47.7% of the patients and were mostly of grade 1 or 2. CONCLUSIONS: The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened progression-free survival among patients with relapsed or refractory multiple myeloma. Daratumumab was associated with infusion-related reactions and a higher rate of neutropenia than the control therapy. Copyright © 2016 Massachusetts Medical Society. All rights reserved.

A twin-experiment is carried out introducing elements of an Ensemble Kalman Filter (EnKF), to assess and correct ocean uncertainties in a high-resolution Bay of Biscay configuration. Initially, an ensemble of 102 members is performed by applying stochastic modeling of the wind forcing. The target of this step is to simulate the envelope of possible realizations and to explore the robustness of the method at building ensemble covariances. Our second step includes the integration of the ensemble-based error estimates into a data assimilative system adopting a 4D Ensemble Optimal Interpolation (4DEnOI) approach. In the twin-experiment context, synthetic observations are simulated from a perturbed member not used in the subsequent analyses, satisfying the condition of an unbiased probability distribution function against the ensemble by performing a rank histogram. We evaluate the assimilation performance on short-term predictability focusing on the ensemble size, the observational network, and the enrichment of the ensemble by inexpensive time-lagged techniques. The results show that variations in performance are linked to intrinsic oceanic processes, such as the spring shoaling of the thermocline, in combination with external forcing modulated by river runoffs and time-variable wind patterns, constantly reshaping the error regimes. Ensemble covariances are able to capture high-frequency processes associated with coastal density fronts, slope currents and upwelling events near the Armorican and Galician shelf break. Further improvement is gained when enriching model covariances by including pattern phase errors, with the help of time-neighbor states augmenting the ensemble spread.

A significant contribution to the improvement of efficiency and lifetime of organic solar cells is due to the successful engineering of the metal contact/organic interface by introducing appropriate interlayers. In the current work we show that a short microwave post-annealing treatment in air of an under-stoichiometric molybdenum oxide (MoOx) hole transport layer significantly enhanced the performance and lifetime of an organic solar cell based on a poly(3-hexylthiophene):[6,6]-phenyl-C71-butyric acid methyl ester (P3HT:PC71BM) blend. The enhanced performance is mainly driven by improvement in the short circuit current (Jsc) and the fill factor (FF), caused by, except for an increase of the anode work function, reduced series resistance, and increased shunt resistance and also higher charge generation efficiency, reduced recombination losses and improved hole transport towards the anode contact. In addition, the lifetime of the devices with microwave annealed MoOx interlayers was also significantly improved compared to those with as-deposited MoOx and, especially, those with the PEDOT-PSS interlayer. The above were attributed to effective dehydration which was also followed by structural transformation and crystallization of the MoOx layer during microwave annealing. The removal of absorbed water molecules led to alterations of the structure and microstructure of the MoOx films, visible in the X-ray diffraction patterns, infrared and Raman spectra and atomic force microscopy images recorded on their surface without influencing the oxide's chemical composition as evidenced by X-ray photoelectron spectroscopy. During microwave annealing the substrate remains practically at room temperature, so the method is applicable for films deposited on plastics or other temperature-sensitive substrates. © 2016 The Royal Society of Chemistry.

We focus in the period of announcement of accounting information for companies listed in an organized market and we re-examine their probability of delisting, voluntarily or not. Adopting the same framework, consideration is given to the assumption that investors utilize market information when accounting data are published. The analysis provided indicates that investors should pay attention to the financial disclosure timing. Our investigation demonstrated that even the short period of three months is quite important to making investment decisions.

In the course of our study on fungal purine transporters, a number of new 3-deazapurine analogues have been rationally designed, based on the interaction of purine substrates with the Aspergillus nidulans FcyB carrier, and synthesized following an effective synthetic procedure. Certain derivatives have been found to specifically inhibit FcyB-mediated [(3)H]-adenine uptake. Molecular simulations have been performed, suggesting that all active compounds interact with FcyB through the formation of hydrogen bonds with Asn163, while the insertion of hydrophobic fragments at position 9 and N6 of 3-deazaadenine enhanced the inhibition.

The detection of periodicity in the broadband non-thermal emission of blazars has so far been proven to be elusive. However, there are a number of scenarios that could lead to quasi-periodic variations in blazar light curves. For example, an orbital or thermal/viscous period of accreting matter around central supermassive black holes could, in principle, be imprinted in the multi-wavelength emission of small-scale blazar jets, carrying such crucial information about plasma conditions within the jet launching regions. In this paper, we present the results of our time series analysis of the ∼9.2 yr long, and exceptionally well-sampled, optical light curve of the BL Lac object OJ 287. The study primarily used the data from our own observations performed at the Mt. Suhora and Kraków Observatories in Poland, and at the Athens Observatory in Greece. Additionally, SMARTS observations were used to fill some of the gaps in the data. The Lomb-Scargle periodogram and the weighted wavelet Z-transform methods were employed to search for possible quasi-periodic oscillations in the resulting optical light curve of the source. Both methods consistently yielded a possible quasi-periodic signal around the periods of ∼400 and ∼800 days, the former with a significance (over the underlying colored noise) of ≥slant 99 % . A number of likely explanations for this are discussed, with preference given to a modulation of the jet production efficiency by highly magnetized accretion disks. This supports previous findings and the interpretation reported recently in the literature for OJ 287 and other blazar sources.

OBJECTIVES: Recent reports have included PALB2 (Partner and localizer of BRCA2) in the growing list of hereditary cancer genes. PALB2 mutations confer a moderate breast cancer risk in heterozygotes and Fanconi anemia in biallelic mutation carriers. PALB2 protein co-localizes with BRCA2 and BRCA1 in nuclear structures and enables error-free homologous recombination repair of double-stranded DNA breaks. This important contribution could be severely diminished if affected by epigenetic mechanisms such as promoter CpG island methylation. The aim of our study was to develop molecular methodologies in order to assess accurately PALB2 expression in breast cancer tissues. DESIGN AND METHODS: DNA and RNA were extracted from 91 sporadic fresh-frozen breast tissues with known histopathological data. DNA was subjected to sodium bisulfite conversion reaction and the CpG island of the PALB2 promoter was analyzed by pyrosequencing. RNA was converted to cDNA and analyzed by a newly developed and validated RT-qPCR assay based on a hydrolysis probe (TaqMan) in the Light Cycler. RESULTS: PALB2 promoter was not methylated in any of the samples tested. 87 out of 91 (95.6%) primary tumors were positive for PALB2 expression, as checked at the mRNA level. When levels of PALB2 mRNA were compared to histopathological data (tumor size, grade, lymph node involvement, metastasis, hormone receptors and HER2 overexpression), no significant statistical correlation was found. CONCLUSIONS: DNA methylation is an unlike mechanism for PALB2 transcriptional regulation. PALB2 mRNA expression does not seem be a promising prognostic biomarker for sporadic breast cancer

Beyond BRCA1 and BRCA2 genes, PALB2 (Partner and localizer of BRCA2) emerges as the third breast cancer susceptibility gene due to its role in the same DNA repair pathway: homologous recombination. In most populations studied so far, PALB2 mutations are detected in 1-2% of BRCA negative female patients. PALB2 gene contains 13 exons; exons 4 and 5 consist 65% of the coding area. We developed a protein truncation test (PTT) for quick screening of truncating pathogenic mutations of these two large exons. Specific primers were de novo, in silico designed and the PTT-PCR products were translated in the presence of biotinylated lysine and detected colorimetrically. The assay was initially tested in 30 patients with hereditary breast cancer, negative for BRCA mutations and then, in 17 patients with the rare medullary breast cancer subtype. Small PALB2 exons were screened with high-resolution melting curve analysis (HRMA) and the large DNA rearrangements with multiplex ligation-dependent probe amplification (MLPA). Any alterations detected were verified by Sanger DNA Sequencing. The developed PTT methodology is highly specific for clinical significant mutations; positive control samples that produce truncated PALB2 peptides were correctly identified and the method was accurate when compared to DNA sequencing. We did not detect any deleterious PALB2 mutation in both groups of patients. HRMA and MLPA were also negative for all tested samples. However, our novel, fast and cost-effective PTT method for pathogenic mutation detection of the two large PALB2 exons can be applied in screening of a large number of breast cancer patients

Corinth Canal is an important technical construction with a significant role in marine and land transportation for Greece. Whilst the main highway of the Corinth bridge is well monitored there is no similar monitoring scheme for landslide failures of the canal walls. This work presents an in-house developed real-time early warning landslide triggering system using wireless sensor network (WSN) nodes. Specifically, for the detection of different types of landslide processes (drift, slide and fall) a set of corresponding MEMS (Micro-Electro-Mechanical Systems) sensors (accelerometer, inclinometer, magnetometer) will be used. These sensors along with radio transmission unit and microprocessor comprise a WSN node. The option for in-situ processing (i.e transmitting only alerts) is possible in order to decrease the communication costs. In conjunction with the proposed WSN system, high accuracy geodetic techniques are used with terrestrial laser scanning (TLS) measurements. TLS is augmenting the point-based system to a spatial -based monitoring system. The paper describes the use of WSN node as triggering device in order to alert the users to begin TLS measurements. A description of the network topology is given along with the implementation of the system in selected control points on the canal walls. Real results are shown and the performance of the system is discussed.

Advanced ovarian cancer (AOC) is one of the leading lethal gynecological cancers in developed countries. Based on the important role of angiogenesis in ovarian cancer oncogenesis and expansion, we hypothesized that the development of an "angiogenic signature" might be helpful in prediction of prognosis and efficacy of anti-angiogenic therapies in this disease. Sixty-nine samples of ascitic fluid- 35 from platinum sensitive and 34 from platinum resistant patients managed with cytoreductive surgery and 1st-line carboplatin-based chemotherapy- were analyzed using the Proteome Profiler™ Human Angiogenesis Array Kit, screening for the presence of 55 soluble angiogenesis-related factors. A protein profile based on the expression of a subset of 25 factors could accurately separate resistant from sensitive patients with a success rate of approximately 90%. The protein profile corresponding to the "sensitive" subset was associated with significantly longer PFS (8 [95% Confidence Interval {CI}: 8-9] vs. 20 months [95% CI: 15-28]; Hazard ratio {HR}: 8.3, p<0.001) and OS (20.5 months [95% CI: 13.5-30] vs. 74 months [95% CI: 36-not reached]; HR: 5.6 [95% CI: 2.8-11.2]; p<0.001). This prognostic performance was superior to that of stage, histology and residual disease after cytoreductive surgery and the levels of vascular endothelial growth factor (VEGF) in ascites. In conclusion, we developed an "angiogenic signature" for patients with AOC, which can be used, after appropriate validation, as a prognostic marker and a tool for selection for anti-angiogenic therapies. © 2016 Trachana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Advanced ovarian cancer (AOC) is one of the leading lethal gynecological cancers in developed countries. Based on the important role of angiogenesis in ovarian cancer oncogenesis and expansion, we hypothesized that the development of an "angiogenic signature" might be helpful in prediction of prognosis and efficacy of anti-angiogenic therapies in this disease. Sixty-nine samples of ascitic fluid- 35 from platinum sensitive and 34 from platinum resistant patients managed with cytoreductive surgery and 1st-line carboplatin-based chemotherapy- were analyzed using the Proteome Profiler™ Human Angiogenesis Array Kit, screening for the presence of 55 soluble angiogenesis-related factors. A protein profile based on the expression of a subset of 25 factors could accurately separate resistant from sensitive patients with a success rate of approximately 90%. The protein profile corresponding to the "sensitive" subset was associated with significantly longer PFS (8 [95% Confidence Interval {CI}: 8-9] vs. 20 months [95% CI: 15-28]; Hazard ratio {HR}: 8.3, p<0.001) and OS (20.5 months [95% CI: 13.5-30] vs. 74 months [95% CI: 36-not reached]; HR: 5.6 [95% CI: 2.8-11.2]; p<0.001). This prognostic performance was superior to that of stage, histology and residual disease after cytoreductive surgery and the levels of vascular endothelial growth factor (VEGF) in ascites. In conclusion, we developed an "angiogenic signature" for patients with AOC, which can be used, after appropriate validation, as a prognostic marker and a tool for selection for anti-angiogenic therapies. © 2016 Trachana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Selective serotonin reuptake inhibitor medication exposure during the perinatal period can have a long term impact in adult offspring on neuroplasticity and the serotonergic system, but the impact of these medications during early development is poorly understood. The aim of this study was to determine the effects of developmental exposure to the SSRI, fluoxetine, on the serotonergic system, dopaminergic system, and synaptophysin density in the prefrontal cortex and hippocampus, as well as number of immature neurons in the dentate gyrus, in juvenile rat offspring at weaning. To model aspects of maternal depression, prenatal restraint stress was used. Sprague-Dawley rat offspring were exposed to either prenatal stress and/or fluoxetine. Main findings show that developmental fluoxetine exposure to prenatally stressed offspring decreased 5-HT and 5-HIAA levels and altered the dopaminergic system in the hippocampus. Prenatal stress, regardless of fluoxetine, increased synaptophysin density in the PFC. This work indicates that early exposure to maternal stress and SSRI medication can alter brain monoamine levels and synaptophysin density in offspring at weaning.

Selective serotonin reuptake inhibitor medication exposure during the perinatal period can have a long term impact in adult offspring on neuroplasticity and the serotonergic system, but the impact of these medications during early development is poorly understood. The aim of this study was to determine the effects of developmental exposure to the SSRI, fluoxetine, on the serotonergic system, dopaminergic system, and synaptophysin density in the prefrontal cortex and hippocampus, as well as number of immature neurons in the dentate gyrus, in juvenile rat offspring at weaning. To model aspects of maternal depression, prenatal restraint stress was used. Sprague-Dawley rat offspring were exposed to either prenatal stress and/or fluoxetine. Main findings show that developmental fluoxetine exposure to prenatally stressed offspring decreased 5-HT and 5-HIAA levels and altered the dopaminergic system in the hippocampus. Prenatal stress, regardless of fluoxetine, increased synaptophysin density in the PFC. This work indicates that early exposure to maternal stress and SSRI medication can alter brain monoamine levels and synaptophysin density in offspring at weaning.

Transporters are transmembrane proteins mediating the selective uptake or efflux of solutes, metabolites, drugs, or ions across cellular membranes. Despite their immense biological importance in cell nutrition, communication, signaling, and homeostasis, their study remains technically difficult mostly due to their lipid-embedded nature. The study of eukaryotic transporters presents additional complexity due to multiple subcellular control mechanisms that operate to ensure proper membrane traffic, membrane localization, and turnover. Model fungi present unique genetic tools to study eukaryotic transporter function. This review highlights how fungal transporter genetics combined with new methodologies for assaying their cellular expression and function as well as recent structural approaches have led to the functional dissection of selected transporter paradigms in Aspergillus nidulans.

We present a strategy for the synthesis of a well-defined rod-coil block copolymers of regioregular poly(3hexylthiophene) and polystyrene (P3HT-b-PS), carrying pendant fullerenes (C60) at precise positions along the PS block. The synthesis is achieved by combining ‘living’ anionic polymerization, Kumada catalyst-transfer polycondensation, and click chemistry. Azide terminated polystyrene was synthesized via anionic polymerization, while C60 moieties were grafted along the coil block with a [4+2] Diels-Alder cycloaddition reaction. The regioregular poly(3-hexylthiophene) rod donor block was end-capped with alkyne and was coupled with the azide terminated polystyrene via a copper catalyzed alkyne-azide cycloaddition. Size exclusion chromatography (SEC), NMR, and FTIR spectroscopies were employed to confirm the synthesis of the diblock copolymers. Furthermore, the end-capping of the ‘living’ polystyrene (PS) with the diphenylethylene cyclobutene (DPE-CB) end-group was confirmed by matrixassisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS). Thermogravimetric analysis (TGA) was employed for the estimation of the C60 content in the block copolymer. The C60 content at the coil block was 22 wt% and a strong quenching of photoluminescence (PL) was observed as the result of the aggregation and percolation structure of the C60 within the PS phase. This behavior indicates that the bonding of C60 across the PS block may offer new routes to engineering stable morphologies, where the degree of aggregation/crystallization of the acceptor material is of paramount importance for stable and efficient electron transport.

The presentation of the findings of this article is based on an action research focused on the supportive role of the school in adolescents’ lives, whereby Religious Education’s contribution to the social and emotional development of adolescents (11-15) is combined with the evaluation of the potential offered by a constructivist approach to the learning process. The research commenced in 2012 and is now in its third year. The project is based on an intervention at a high school in an impoverished suburb of Athens and researches educational practices through interpretative-ethnographic methods. The researcher has attempted to answer the question of whether the design of the learning environments is effective not only in the learning process, but also on inter-communication and “connectedness” between the members of the learning community. The findings so far indicate a correlation between adolescents’ emotional and social wellbeing and the school’s approach to knowledge and learning methods, specifically in Religious Education classes. It is fair to say, however, that there exist ethnic, social and family components that are negatively related to a sense of “connectedness” within the school although at the same time Religious Education as a subject is, however, found to be positively related to learning community atmosphere.

Advances in immunotherapy have changed the therapeutic landscape in many malignancies. Immune checkpoint inhibitors have already received regulatory approval in melanomas, lung, renal and bladder carcinomas. A common feature of these neoplasms is the increased mutational load, related to a possible increase number of tumor neoantigens that are recognized by the immune system. The mechanisms that DNA damage could confer to the mutational load and the formation of neoantigens and how this could be exploited to advance our immunotherapeutic strategies is discussed in this review. © Annals of Translational Medicine.

Advances in immunotherapy have changed the therapeutic landscape in many malignancies. Immune checkpoint inhibitors have already received regulatory approval in melanomas, lung, renal and bladder carcinomas. A common feature of these neoplasms is the increased mutational load, related to a possible increase number of tumor neoantigens that are recognized by the immune system. The mechanisms that DNA damage could confer to the mutational load and the formation of neoantigens and how this could be exploited to advance our immunotherapeutic strategies is discussed in this review. © Annals of Translational Medicine.

DNA repair activity of malignant cells seems to influence therapeutic outcome and patients' survival. Herein, we investigated the mechanistic basis for the link between DNA repair efficiency and response to antimyeloma therapy. Nucleotide excision repair (NER), interstrand cross-links repair (ICL/R), double-strand breaks repair (DSB/R), and chromatin structure were evaluated in multiple myeloma (MM) cell lines (melphalan-sensitive RPMI8226; melphalan-resistant LR5) and bone marrow plasma cells (BMPCs) from MM patients who responded (n = 17) or did not respond (n = 9) to subsequent melphalan therapy. The effect of DSB/R inhibition was also evaluated. Responders' BMPCs showed slower rates of NER and DSB/R (P < .0022), similar rates of ICL/R, and more condensed chromatin structure compared with nonresponders. Moreover, apoptosis rates of BMPCs were inversely correlated with individual DNA repair efficiency and were higher in responders' cells compared with those of nonresponders (P = .0011). Similarly, RPMI8226 cells showed slower rates of NER and DSB/R, comparable rates of ICL/R, more condensed chromatin structure, and higher sensitivity than LR5 cells. Interestingly, cotreatment of BMPCs or cell lines with DSB/R inhibitors significantly reduced the rates ofDSB/R and increasedmelphalan sensitivity of the cells, with the nonhomologous end-joining inhibitor SCR7 showing the strongest effect. Together, responders' BMPCs are characterized by lower efficiencies of NER and DSB/R mechanisms, resulting in higher accumulation of the extremely cytotoxic ICLs andDSBs lesions,which in turn triggers the induction of the apoptotic pathway. Moreover, the enhancement of melphalan cytotoxicity by DSB/R inhibition offers a promising strategy toward improvement of existing antimyeloma regimens. © 2016 by The American Society of Hematology.

DNA repair activity of malignant cells seems to influence therapeutic outcome and patients' survival. Herein, we investigated the mechanistic basis for the link between DNA repair efficiency and response to antimyeloma therapy. Nucleotide excision repair (NER), interstrand cross-links repair (ICL/R), double-strand breaks repair (DSB/R), and chromatin structure were evaluated in multiple myeloma (MM) cell lines (melphalan-sensitive RPMI8226; melphalan-resistant LR5) and bone marrow plasma cells (BMPCs) from MM patients who responded (n = 17) or did not respond (n = 9) to subsequent melphalan therapy. The effect of DSB/R inhibition was also evaluated. Responders' BMPCs showed slower rates of NER and DSB/R (P < .0022), similar rates of ICL/R, and more condensed chromatin structure compared with nonresponders. Moreover, apoptosis rates of BMPCs were inversely correlated with individual DNA repair efficiency and were higher in responders' cells compared with those of nonresponders (P = .0011). Similarly, RPMI8226 cells showed slower rates of NER and DSB/R, comparable rates of ICL/R, more condensed chromatin structure, and higher sensitivity than LR5 cells. Interestingly, cotreatment of BMPCs or cell lines with DSB/R inhibitors significantly reduced the rates ofDSB/R and increasedmelphalan sensitivity of the cells, with the nonhomologous end-joining inhibitor SCR7 showing the strongest effect. Together, responders' BMPCs are characterized by lower efficiencies of NER and DSB/R mechanisms, resulting in higher accumulation of the extremely cytotoxic ICLs andDSBs lesions,which in turn triggers the induction of the apoptotic pathway. Moreover, the enhancement of melphalan cytotoxicity by DSB/R inhibition offers a promising strategy toward improvement of existing antimyeloma regimens. © 2016 by The American Society of Hematology.

A literature review was conducted to present if travellers accept the mobile healthcare (m-Health) technologies. The research was run on international scientific databases using certain keywords to cover the content of the review. From the online search results, 21 publications were selected which combine the "m-Health", "travellers" and "technology acceptance" topics. The majority of the papers are using the Technology Acceptance Model (or a variation of it) on their methodology. Only few papers discuss about the above three topics simultaneously. All of the publications highlight the acceptance of the mobile technologies by their users. Based on this, it can be assumed that travellers may accept the m-Health applications. Further investigation is needed on this subject to give more accurate results.

BACKGROUND: The objective of this study was to investigate whether multistranded fixed retainers prevented overeruption of unopposed mandibular second molars in maxillary first molar extraction cases. METHODS: The panoramic radiographs of 65 Class II Division 1 Caucasian Whites (28 females, 37 males) consecutively treated with bilateral maxillary first molar extraction and the Begg technique, and with records taken after treatment (T1) and in retention (T2), were withdrawn from private practice records. After appliance removal, mandibular second molars were retained with sectional wires till at least T2 in case of lack of occlusal contact with the antagonist. The subjects were assigned to study-retention and control-nonretention groups based on the retention status of mandibular second molars. Radiographic analysis was carried out to determine inclination of mandibular molars and the resulting movement of second molar centroids. Parametric and nonparametric tests were performed to assess the changes between T1 and T2. RESULTS: No statistically significant differences in molar inclination were observed between groups and timepoints (P > 0.05). There were no statistically significant differences in molar movement percentages (P > 0.05) irrespective of whether fixed retention had been used or not. CONCLUSIONS: No significant eruption occurred in unopposed mandibular second molars bonded with fixed sectional retainers compared to molars partially occluded with the antagonists without fixed retention. Given the study limitations, fixed retention should be considered with caution in restricting tooth overeruption in unopposed molars.

We report on the influence of elastic waves on the optical response and light emission in simultaneously photonic and phononic resonant cavities. Elastic waves couple with light through the acousto-optic interaction. Concurrent control of both light and sound through simultaneously photonic–phononic, often called phoxonic, band-gap structures is intended to advance both our understanding as well as our ability to manipulate light with sound and vise versa. In particular, co-localization of light and sound in phoxonic cavities could trigger nonlinear absorption and emission processes and lead to enhanced acousto-optic effects. We review our recent work on sound-controlled optical response and light emission in phoxonic cavities and investigate the limits of validity of the photoelastic model that describes light–sound interaction to first-order approximation. Moreover we present some preliminary results on silicon nitride nanobeam phoxonic devices.

The frequency ω dependent storage G′(ω) and loss G″(ω) moduli of star-shaped polystyrene (SPS) molecules of a range of functionalities f and molecular weights per arm Ma were measured under small amplitude oscillatory shear conditions. Star-shaped macromolecules are composed of an inner region, core, where the chain segments are stretched and the “packing” density is higher than that of the outer region, corona. The frequency dependencies of G′(ω) and G″(ω) for low functionality molecules (f<8) with long arms Ma are well described by the model of Milner and McLeish, indicating that the translational dynamics are facilitated by an arm retraction mechanism. With increasing values of f and decreasing Ma the model failsthe arm retraction process is no longer validdue largely to the increasing size of the core in relation to the overall size of the molecule. The molecules exhibit evidence of spatial structural order due to entropic, intermolecular interactions, and the translational dynamics of these molecules occur via a cooperative process, akin to that of soft colloids, for sufficiently large values of f and small Ma. The overall dynamics may be summarized in a diagram delineating different mechanisms that facilitate flow as a function of f and Ma. 

PURPOSE: The aim of the study was to investigate the effects of low-intensity running performed immediately after lower-body power-training sessions on power development. METHODS: Twenty young females participated in 6 weeks, 3/week, of either lower body power training (PT) or lower body power training followed by 30 min of low-intensity running (PET) eliciting 60-70 % of maximal heart rate. The following were measured before and after the training period: counter-movement jump, isometric leg press force and rate of force development (RFD), half squat 1-RM, vastus lateralis fiber type composition and cross sectional area, resting intramuscular fiber conduction velocity (MFCV), and heart rate during the modified Bruce treadmill test. RESULTS: Counter-movement jump height and peak power increased after PT (10.7 ± 6.2 and 12.9 ± 18.7 %, p < 0.05) but not after PET (3.4 ± 7.6 and 5.11 ± 10.94 %, p > 0.05). Maximum isometric force, RFD, and half squat 1-RM increased similarly in both groups. Muscle fiber type composition was not altered in either group. Muscle fiber cross sectional area increased only after PT (17.5 ± 17.4, 14.5 ± 10.4, 20.36 ± 11.3 %, in type I, IIA, and IIX fibers, respectively, p < 0.05). Likewise, mean MFCV increased with PT only (before: 4.53 ± 0.38 m s(-1), after: 5.09 ± 0.39 m s(-1), p = 0.027). Submaximal heart rate during the Bruce treadmill test remained unchanged after PT but decreased after PET. CONCLUSION: These results suggest that low-intensity running performed after lower-body power training impairs the exercise-induced adaptation in stretch-shortening cycle jumping performance (vertical jump height, peak power), during the first 6 weeks of training, which may be partially linked to inhibited muscle fiber hypertrophy and muscle fiber conduction velocity.

A series of experiments was carried out to investigate any structural or biochemical alterations on Arabidopsis thaliana (Col.) plants after a long term exposure to non ionizing radiation emitted from the base unit of a cordless DECT system. Exposed plants, compared to their control counterparts, seem to be affected concerning their biomass and leaf structure. Their leaves are thinner and possess fewer chloroplasts. SEM observations of the exposed leaves reveal that the only feature affected is the pubescence which almost disappears while TEM investigation revealed minor structural effects in the chloroplasts. The reduction in the number of chloroplasts as well as the decrease of stroma thylakoids and photosynthetic pigments are probably the main reasons for a weak photosynthetic potential and a consequent reduction of the biomass production. © 2016 Elsevier GmbH.

Kenaf (Hibiscus cannabinus L.) was experimentally cultivated with the use of digested, dried sewage sludge (130 t/ha) and water from a municipal Sewage Treatment Plant (STP) in order to assess their potential to replace conventional fertilization (100 kg N/ha, 75 kg P2O5/ha and 75 kg Κ2O/ha) and irrigation. Tap water and treated wastewater were used for irrigation in quantities corresponding to 6500 m3/ha. Four different treatment combinations were applied as follows: (a) wastewater irrigation and conventional fertilization, (b) wastewater irrigation and sewage sludge fertilization, (c) tap water irrigation and sewage sludge fertilization, and (d) tap water irrigation and conventional fertilization. The dry plant biomass collected in the final harvest (140 days after plant emergence) from the four treatment plots was 12.3 t/ha, 12.6 t/ha, 12.4 t/ha and 12.8 t/ha respectively. These differences were not statistically significant (ANOVA, P = 0.05) and, therefore, it was concluded that the use of municipal wastes had similar effects on dry biomass production with that of conventional fertilization. An earlier harvest (125 days after plant emergence) gave 11.3% lower dry biomass on average in relation to the second harvest, and this difference was statistically significant (ANOVA, P = 0.05). Premature harvest may lead to significant biomass losses, so the plant must be collected during its technological maturity stage. There was not any statistically significant difference among the four treatments and between the two harvests in fiber dimensions and derived values (suitability indices for paper manufacture). On the other hand, cellulose and lignin content in the second harvest were significantly higher compared to the first one, whereas no significant differences were detected among the four treatments. © 2016 Elsevier B.V.

Hydroxymethyl ketones are useful auxiliaries in organic synthesis and are also found in several medicinal agents. N-Heterocyclic carbenes (NHCs) have been used in the literature in order to introduce the hydroxymethyl group into aromatic aldehydes in good yields, but they are not that successful for aliphatic aldehydes. In the present work, the use of microwave irradiation has been efficiently incorporated into this organocatalytic synthesis of aromatic, but more importantly of aliphatic hydroxymethyl ketones that can be used as precursors for medicinally interesting compounds.

Resumen: En la novela Aluvión de fuego de Óscar Cerruto se tocan varios aspectos de la sociedad boliviana relacionados con la guerra del Chaco. Se realiza una crítica aguda del sistema político que fue la causa de una guerra absurda y de las injusticias que sufren las capas más desfavorecidas de la población boliviana. El entorno físico juega un papel importante, ya que, aparte de ser el casus belli de la guerra, define la vida y la mentalidad de los personajes, especialmente de los indígenas y los mineros. A través del recorrido del joven protagonista, un rico burgués, por el vasto territorio boliviano se revela una sociedad en crisis debida a la falta de comunicación que caracteriza la clase dominante y los indios. Cerruto cuestiona la situación política y social, mientras que expresa la necesidad de la formación de una conciencia nacional en el pueblo boliviano. Abstract: The Oscar Cerruto´s novel, Aluvión de fuego, presents various aspects of the Bolivian society related to the Chaco War; it condemns the political situation, which is responsible for the absurd war and the injustices the lower social classes suffered. The natural environment setting of the novel is of special importance, because it is the casus belli and defines the life and the whole mentality of the characters, especially of the Indians and miners. The young protagonist´s tour of the vast Bolivian territory, who is a rich bourgeois, shows a society in crisis because of the lack of communication between the ruling class and the Indians. Cerruto questions the political and social situation and expresses the need to form a national consciousness in the Bolivian people.

This paper presents a comparison between e-Learning and traditional learning methods of a University course on Health Informatics domain. A pilot research took place among University students who divided on two learning groups, the e-learners and the traditional learners. A comparison of the examinations' marks for the two groups of students was conducted in order to find differences on students' performance. The study results reveal that the students scored almost the same marks independently of the learning procedure. Based on that, it can be assumed that the e-learning courses have the same effectiveness as the in-classroom learning sessions.

We employ two tight-binding (TB) approaches to systematically study the electronic structure and hole or electron transfer in B-DNA monomer polymers and dimer polymers made up of N monomers (base pairs): (I) at the base-pair level, using the onsite energies of base pairs and the hopping integrals between successive base pairs, i.e., a wire model and (II) at the single-base level, using the onsite energies of the bases and the hopping integrals between neighboring bases, i.e., an extended ladder model since we also include diagonal hoppings. We solve a system of M (matrix dimension) coupled equations [(I) M=N, (II) M=2N] for the time-independent problem, and a system of M coupled first order differential equations for the time-dependent problem. We perform a comparative study of stationary and time-dependent aspects of the two TB variants, using realistic sets of parameters. The studied properties include HOMO and LUMO eigenspectra, occupation probabilities, density of states and HOMO-LUMO gaps as well as mean over time probabilities to find the carrier at each site [(I) base pair or (II) base], Fourier spectra, which reflect the frequency content of charge transfer, and pure mean transfer rates from a certain site to another. The two TB approaches give coherent, complementary aspects of electronic properties and charge transfer in B-DNA monomer polymers and dimer polymers.

This volume brings together a variety of approaches to the different ways in which the role of animals was understood in ancient Greco-Roman myth and religion, across a period of several centuries, from Preclassical Greece to Late Antique Rome. Animals in Greco-Roman antiquity were thought to be intermediaries between men and gods, and they played a pivotal role in sacrificial rituals and divination, the foundations of pagan religion. The studies in the first part of the volume examine the role of the animals in sacrifice and divination. The second part explores the similarities between animals, on the one hand, and men and gods, on the other. Indeed, in antiquity, the behaviour of several animals was perceived to mirror human behaviour, while the selection of the various animals as sacrificial victims to specific deities often was determined on account of some peculiar habit that echoed a special attribute of the particular deity. The last part of this volume is devoted to the study of animal metamorphosis, and to this end a number of myths that associate various animals with transformation are examined from a variety of perspectives.

ABSTRACT: Introduction: Monoclonal antibodies mark the beginning of a new era in the context of multiple myeloma (MM) treatment. Numerous antibodies have been tested or are currently in development for patients with MM, in order to improve tolerability and quality of life. Areas covered: This manuscript reviews emerging antibodies for the treatment of MM i.e. elotuzumab, daratumumab, MOR03087, isatuximab, bevacizumab, cetuximab, siltuximab, tocilizumab, elsilimomab, azintrel, rituximab, tositumomab, milatuzumab, lucatumumab, dacetuzumab, figitumumab, dalotuzumab, AVE1642, tabalumab, pembrolizumab, pidilizumab, nivolumab. Expert opinion: Amongst these antibodies, elotuzumab which targets SLAMF-7 and daratumumab which targets CD38, have been recently approved by FDA for patients with relapsed/refractory MM. Both agents are well tolerated. Multiple clinical trials incorporating these monoclonal antibodies in MM treatment are currently ongoing. Of special interest are the anticipated results of phase III clinical trials with elotuzumab [NCT0189164; NCT01335399; NCT02495922] and daratumumab [NCT02252172; NCT02195479] in newly diagnosed MM patients. Moreover, of great interest are the awaited data on pembrolizumabin combination with pomalidomide and dexamethasone in refractory/relapsed MM patients [NCT02576977] and in combination with lenalidomide and dexamethasone in newly diagnosed MM patients. It seems that the incorporation of monoclonal antibodies will change the landscape of myeloma therapy in the near future. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

ABSTRACT: Introduction: Monoclonal antibodies mark the beginning of a new era in the context of multiple myeloma (MM) treatment. Numerous antibodies have been tested or are currently in development for patients with MM, in order to improve tolerability and quality of life. Areas covered: This manuscript reviews emerging antibodies for the treatment of MM i.e. elotuzumab, daratumumab, MOR03087, isatuximab, bevacizumab, cetuximab, siltuximab, tocilizumab, elsilimomab, azintrel, rituximab, tositumomab, milatuzumab, lucatumumab, dacetuzumab, figitumumab, dalotuzumab, AVE1642, tabalumab, pembrolizumab, pidilizumab, nivolumab. Expert opinion: Amongst these antibodies, elotuzumab which targets SLAMF-7 and daratumumab which targets CD38, have been recently approved by FDA for patients with relapsed/refractory MM. Both agents are well tolerated. Multiple clinical trials incorporating these monoclonal antibodies in MM treatment are currently ongoing. Of special interest are the anticipated results of phase III clinical trials with elotuzumab [NCT0189164; NCT01335399; NCT02495922] and daratumumab [NCT02252172; NCT02195479] in newly diagnosed MM patients. Moreover, of great interest are the awaited data on pembrolizumabin combination with pomalidomide and dexamethasone in refractory/relapsed MM patients [NCT02576977] and in combination with lenalidomide and dexamethasone in newly diagnosed MM patients. It seems that the incorporation of monoclonal antibodies will change the landscape of myeloma therapy in the near future. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

This study provides new evidence on emerging stock market contagion during the Global Financial crisis (GFC) and the Euro zone Sovereign Debt Crisis (ESDC). Focusing on the three emerging Baltic markets and developed European markets, proxied by the EUROSTOXX50 stock index, we explore asymmetric dynamic conditional correlation dynamics across stable and crisis periods. Empirical evidence indicates a diverse contagion pattern for the Baltic region across the two crises. Latvia and Lithuania were contagious during the GFC, while they were insulated from the adverse effects of the ESDC. On the other hand, Estonia decoupled from the negative consequences during the global turmoil period, but recoupled during the ESDC. The results could be attributed to financial and macroeconomic characteristics of the Baltic countries before and after the turmoil periods and the introduction time of the Euro as a national currency.

Collective hybridized plasmon modes, which enable strong magnetooptical coupling and consequent enhanced Faraday effect in three-dimensional periodic assemblies of magnetic dielectric nanoparticles coated with a noble-metal shell, are studied by means of rigorous full electrodynamic calculations using an extension of the layer-multiple-scattering method, in conjunction with the effective-medium approximation. A thorough analysis of relevant photonic dispersion diagrams and transmission spectra provides a consistent explanation of the underlying physical mechanisms to a degree that goes beyond existing interpretation. It is shown that properly designed structures of such composite magnetoplasmonic nanoparticles offer a versatile platform for engineering increased and broadband Faraday rotation.

From 1979 to 1989, ten million tons of phosphogypsum, a waste by-product of the Greek phosphate fertilizer industry, was disposed into an abandoned limestone quarry in Schistos former waste site, Piraeus (Greece). The quarry has been recently closed and remediated using geomembranes and thick soil cover with vegetation. A part of the deposited phosphogypsum has been exposed due to intense rainfall episodes leading to concerns about how could potentially released radioactivity affect the surrounding environment. This study seeks to assess the environmental impact of the phosphogypsum deposited in the Schistos quarry, using laboratory-based $\gamma$-ray spectrometry measurements and geographical information systems. Radioactivity concentrations were mapped onto spatial-data to yield a spatial-distribution of radioactivity in the area. The data indicate elevated 226Ra concentrations in a specific area on the steep south-eastern cliff of the remediated waste site that comprises uncovered phosphogypsum and is known to be affected by local weather conditions. 226Ra concentrations range from 162 to 629 Bq/kg, with an average activity being on the low side, compared to the global averages for phosphogypsum. Nevertheless, the low environmental risk may be minimized by remediating this area with geomembranes and thick soil cover with vegetation, a technique, which has worked successfully over the remainder of the remediated quarry.

{The main objective of this work is the assessment of the annual number of hospital admissions for respiratory disease (HARD) due to the exposure to inhalable particulate matter (PM10), within the greater Athens area (GAA), Greece. Towards this aim, the time series of the particulate matter with aerodynamic diameter less than 10 mu m (PM10) recorded in six monitoring stations located in the GAA, for a 13-year period 2001-2013, is used. In this study AirQ2.2.3 software developed by the WHO, was used to evaluate adverse health effects by PM10 in the GAA during the examined period. The results show that, the mean annual HARD cases per 100,000 inhabitants ranged between 20 (suburban location) and 40 (city centre location). Approximately 70 % of the annual HARD cases are due to city centre residents. In all examined locations, a declining trend in the annual number of HARD cases is appeared. Moreover, a strong relation between the annual number of HARD cases and the annual number of days exceeding the European Union daily PM10 threshold value was found.}

In this paper a re-analysis of previous research concerning an uplifted tidal notch developed near the modern harbor of Poros (eastern Cephalonia Island, Ionian Sea, Greece) is undertaken. According to radiocarbon dating, this notch was active between the 4th–6th century AD and 1953 AD, i.e. for at least 1450 years. Recent measurements have shown that the inward depth of the notch profile at well preserved sites is 93 cm. This permits an estimate of the average rate of intertidal bioerosion to 0.64 mm/a for this time period.

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at ∈ European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better fu treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. © 2016 Ferrata Storti Foundation.

PURPOSE: Programmed death-ligand 1 (PD-L1; also known as CD274 or B7-H1) expression represents a mechanism of immune escape for cancer. Our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in primary laryngeal squamous cell carcinomas (SCC). EXPERIMENTAL DESIGN: A well-annotated cohort of 260 operable primary laryngeal SCCs [formalin-fixed paraffin-embedded (FFPE) specimens] was morphologically characterized for stromal tumor-infiltrating lymphocytes (TIL), on hematoxylin/eosin-stained whole sections and for PD-L1 mRNA expression by qRT-PCR in FFPE specimens. For PD-L1 protein expression, automated quantitative protein analysis (AQUA) was applied on tissue microarrays consisting of two cores from these tumors. In addition, PD-L1 mRNA expression in fresh-frozen tumors and normal adjacent tissue specimens was assessed in a second independent cohort of 89 patients with primary laryngeal SCC. RESULTS: PD-L1 mRNA levels were upregulated in tumors compared with surrounding normal tissue (P = 0.009). TILs density correlated with tumor PD-L1 AQUA levels (P = 0.021). Both high TILs density and high PD-L1 AQUA levels were significantly associated with superior disease-free survival (DFS; TILs: P = 0.009 and PD-L1: P = 0.044) and overall survival (OS; TILs: P = 0.015 and PD-L1: P = 0.059) of the patients and retained significance in multivariate analysis. CONCLUSIONS: Increased TILs density and PD-L1 levels are associated with better outcome in laryngeal squamous cell cancer. Assessment of TILs and PD-L1 expression could be useful to predict response to immune checkpoint inhibitors.

We used thiol-based antioxidant supplementation (n-acetylcysteine, NAC) to determine whether immune mobilisation following skeletal muscle microtrauma induced by exercise is redox-sensitive in healthy humans. According to a two-trial, double-blind, crossover, repeated measures design, 10 young men received either placebo or NAC (20mg/kg/day) immediately after a muscledamaging exercise protocol (300 eccentric contractions) and for eight consecutive days. Blood sampling and performance assessments were performed before exercise, after exercise, and daily throughout recovery. NAC reduced the decline of reduced glutathione in erythrocytes and the increase of plasma protein carbonyls, serum TAC and erythrocyte oxidized glutathione, and TBARS and catalase activity during recovery thereby altering postexercise redox status. The rise of muscle damage and inflammatory markers (muscle strength, creatine kinase activity, CRP, proinflammatory cytokines, and adhesion molecules) was less pronounced in NAC during the first phase of recovery. The rise of leukocyte and neutrophil count was decreased by NAC after exercise. Results on immune cell subpopulations obtained by flow cytometry indicated that NAC ingestion reduced the exerciseinduced rise of total macrophages, HLA+ macrophages, and 11B+ macrophages and abolished the exercise-induced upregulation of B lymphocytes. Natural killer cells declined only in PLA immediately after exercise. These results indicate that thiol-based antioxidant supplementation blunts immune cell mobilisation in response to exercise-induced inflammation suggesting that leukocyte mobilization may be under redox-dependent regulation. Copyright © 2016 Alexandra Sakelliou et al.

Maintenance and accurate propagation of the genetic material are key features for physiological development and wellbeing. The replication licensing machinery is crucial for replication precision as it ensures that replication takes place once per cell cycle. Thus, the expression status of the components comprising the replication licensing apparatus is tightly regulated to avoid re-replication; a form of replication stress that leads to genomic instability, a hallmark of cancer. In the present review we discuss the mechanistic basis of replication licensing deregulation, which leads to systemic effects, exemplified by its role in carcinogenesis and a variety of genetic syndromes. In addition, new insights demonstrate that above a particular threshold, the replication licensing factor Cdc6 acts as global transcriptional regulator, outlining new lines of exploration. The role of the putative replication licensing factor ChlR1/DDX11, mutated in the Warsaw Breakage Syndrome, in cancer is also considered. Finally, future perspectives focused on the potential therapeutic advantage by targeting replication licensing factors, and particularly Cdc6, are discussed.

Purpose: To identify prognostic molecular profiles in patients with mRCC treated with sunitinib, we performed immunohistochemical analysis for VEGF and PI3K/Akt/mTOR pathway components. Methods: The immunohistochemical expression of VEGF, p85α, p110γ, PTEN, p-Akt, p-mTOR, p-4E-BP1 and p-p70S6K was studied in 79 patients with mRCC who received first-line treatment with sunitinib. Expression was correlated with clinicopathological features and survival. Results: VEGF was highly expressed (median H-Score 150), while positivity for the markers of the PI3K/Akt/mTOR pathway was: p85α 43/66 (65 %), p110γ41/60 (68 %), PTEN 32/64 (50 %), p-Akt57/63 (90 %), p-mTOR48/64 (75 %), p-4E-BP1 58/64 (90 %) and p-p70S6K 60/65 (92 %). No single immunohistochemical marker was found to have prognostic significance. Instead, the combination of increased p-mTOR and low VEGF expression was adversely correlated with overall survival (OS) (3.2 vs. 16.9 months, P = 0.001). Conclusion: Immunohistochemistry for VEGF and p-mTOR proteins may discriminate patients refractory to first-line sunitinib with poor prognosis. Prospective validation of our findings is needed. © 2016 Springer-Verlag Berlin Heidelberg

Purpose: To identify prognostic molecular profiles in patients with mRCC treated with sunitinib, we performed immunohistochemical analysis for VEGF and PI3K/Akt/mTOR pathway components. Methods: The immunohistochemical expression of VEGF, p85α, p110γ, PTEN, p-Akt, p-mTOR, p-4E-BP1 and p-p70S6K was studied in 79 patients with mRCC who received first-line treatment with sunitinib. Expression was correlated with clinicopathological features and survival. Results: VEGF was highly expressed (median H-Score 150), while positivity for the markers of the PI3K/Akt/mTOR pathway was: p85α 43/66 (65 %), p110γ41/60 (68 %), PTEN 32/64 (50 %), p-Akt57/63 (90 %), p-mTOR48/64 (75 %), p-4E-BP1 58/64 (90 %) and p-p70S6K 60/65 (92 %). No single immunohistochemical marker was found to have prognostic significance. Instead, the combination of increased p-mTOR and low VEGF expression was adversely correlated with overall survival (OS) (3.2 vs. 16.9 months, P = 0.001). Conclusion: Immunohistochemistry for VEGF and p-mTOR proteins may discriminate patients refractory to first-line sunitinib with poor prognosis. Prospective validation of our findings is needed. © 2016 Springer-Verlag Berlin Heidelberg

Objective: To explore the correlation between the expression of α5-integrin, α7-integrin, Ε-cadherin, and N-cadherin in prostate cancer (PCa) and its clinicopathological data including tumor grade and clinical stage. Methods: The expression of α5-integrin, α7-integrin, Ε-cadherin, and N-cadherin was examined in 157 cases of PCa and adjacent normal prostatic tissue by immunohistochemical assay, and the correlation with clinicopathological features was analyzed. Results: Expressions of α5-integrin, α7-integrin, and Ε-cadherin in PCa were lower than those in normal prostatic tissues (P<0.05). N-cadherin expression was higher in cancer prostatic tissue than in normal prostatic tissues (P<0.05). The reduced expression of α5-integrin, α7-integrin, and Ε-cadherin was related to Gleason score, pathological stage, lymph node metastasis, and prostate-specific antigen level, but it was not associated with positive surgical margins and patient age. The increased expression of N-cadherin was related to Gleason score, pathological stage, lymph node metastasis, and prostate-specific antigen level, but not to age and positive surgical margins. The expression of E-cadherin was highly negatively correlated with that of N-cadherin and also positively correlated with that of α5-integrin and α7-integrin. Conclusion: The reduced expression of α5-integrin, α7-integrin, and Ε-cadherin and abnormal expression of N-cadherin play an important role in the occurrence and development of PCa. The results indicate that these have potential values in the diagnosis and are predictable indices in the proliferation of PCa. © 2016 Elsevier Inc.

Objective: To explore the correlation between the expression of α5-integrin, α7-integrin, Ε-cadherin, and N-cadherin in prostate cancer (PCa) and its clinicopathological data including tumor grade and clinical stage. Methods: The expression of α5-integrin, α7-integrin, Ε-cadherin, and N-cadherin was examined in 157 cases of PCa and adjacent normal prostatic tissue by immunohistochemical assay, and the correlation with clinicopathological features was analyzed. Results: Expressions of α5-integrin, α7-integrin, and Ε-cadherin in PCa were lower than those in normal prostatic tissues (P<0.05). N-cadherin expression was higher in cancer prostatic tissue than in normal prostatic tissues (P<0.05). The reduced expression of α5-integrin, α7-integrin, and Ε-cadherin was related to Gleason score, pathological stage, lymph node metastasis, and prostate-specific antigen level, but it was not associated with positive surgical margins and patient age. The increased expression of N-cadherin was related to Gleason score, pathological stage, lymph node metastasis, and prostate-specific antigen level, but not to age and positive surgical margins. The expression of E-cadherin was highly negatively correlated with that of N-cadherin and also positively correlated with that of α5-integrin and α7-integrin. Conclusion: The reduced expression of α5-integrin, α7-integrin, and Ε-cadherin and abnormal expression of N-cadherin play an important role in the occurrence and development of PCa. The results indicate that these have potential values in the diagnosis and are predictable indices in the proliferation of PCa. © 2016 Elsevier Inc.

Silicoflagellate abundance, vertical distribution and morphology were studied during spring (March 2014) at three sampling stations locatedin the Northeast Aegean Sea adjacent to the Dardanelles Strait and characterized by a variable influx of cold, low-salinity Black Sea water.The silicoflagellate assemblage was dominated by Dictyocha stapedia and Stephanocha speculum with minor contribution of D. aculeata andOctactis pulchra. While specimens of D. stapedia were represented by the typical morphologies described in other areas of the Mediterranean Sea,populations of S. speculum displayed peculiar characters: they were large, predominantly 7-sided, with a small apical ring as well as apical ringspines, concave basal ring sides and non-rotated apical structure. Some of these features have been described for S. speculum at high latitudes, butthe combined characters make these specimens slightly different from the high latitude populations. Similar morphologies have been observed inthe western Black Sea, thus we can infer that the peculiar specimens detected in the Northeast Aegean are associated with the influx of Black Seawater masses.

The Fermi surfaces and Elliott-Yafet spin-mixing parameter (EYP) of several elemental metals are studied by ab initio calculations. We focus first on the anisotropy of the EYP as a function of the direction of the spin-quantization axis {[}B. Zimmermann et al., Phys. Rev. Lett. 109, 236603 (2012)]. We analyze in detail the origin of the gigantic anisotropy in 5d hcp metals as compared to 5d cubic metals by band structure calculations and discuss the stability of our results against an applied magnetic field. We further present calculations of light (4d and 3d) hcp crystals, where we find a huge increase of the EYP anisotropy, reaching colossal values as large as 6000% in hcp Ti. We attribute these findings to the reduced strength of spin-orbit coupling, which promotes the anisotropic spin-flip hot loops at the Fermi surface. In order to conduct these investigations, we developed an adapted tetrahedron-based method for the precise calculation of Fermi surfaces of complicated shape and accurate Fermi-surface integrals within the full-potential relativistic Korringa-Kohn-Rostoker Green function method.

There are limited data on fetuin-A, soluble leptin receptor (sOB-R) and free leptin index (FLI) in patients with chronic lymphocytic leukemia (CLL). The aim of this study was to compare circulating fetuin-A, sOB-R levels and FLI between 95 patients with CLL and 95 matched controls, as well as among different stages of CLL. Circulating fetuin-A was significantly lower in cases than controls (241.9 ± 99.2 vs. 288.8 ± 127.7 μg/mL; p = 0.005). Although circulating sOB-R levels were similar between groups, FLI was lower in cases than controls (0.45 ± 0.42 vs. 0.67 ± 0.57; p = 0.003). Furthermore, lower fetuin-A or FLI, but not sOB-R, were independently associated with CLL (p < 0.05), particularly among overweight/obese individuals. Fetuin-A, s-OB-R and FLI were similar between different stages of CLL severity, or between symptomatic and asymptomatic disease. In conclusion, circulating fetuin-A and FLI, but not sOB-R, were lower in patients with CLL than controls, a finding warranting further investigation.

A number of software applications for the practice of the singing voice have been introduced the last decades, but all of them are limited to equal tempered scales. In this work, we present the design and development of FONASKEIN, a novel modular interactive software application for the practice of singing voice in real time and with visual feedback for both equal and non-equal tempered scales. Details of the Graphical User Interface of FONASKEIN are given, along with its architecture. The evaluation results of FONASKEIN in a pilot experiment with eight participants and with four songs in various musical scales showed its positive effect in practice of the singing voice in all cases.

Saronikos Gulf, including the industrial zone of Elefsis Bay and the Port of Piraeus, is one of the most anthropogenically impacted coastal regions of Greece. Distinct assemblages of benthic foraminifers in sediment samples, collected from this gulf in February 2012, defined three zones that reflect abiotic parameters of the sediments (e.g., organic carbon, metal content). A low-diversity assemblage, dominated by stress-tolerantAmmonia tepida and Bulimina spp., was characteristic of samples from Elefsis Bay. Samples from the western and central part of Saronikos Gulf were the most variable with respect to both abiotic parameters and the foraminiferal assemblage, characterized by a mix of stress-tolerant and more sensitive taxa, especially Bolivina spp. andNonion fabum. Samples from the coast of Salamis and at the eastern sector of the gulf were characterized by a diverse assemblage that included Peneroplis pertusus, miliolids, and a variety of small, epiphytic rotaliid taxa. A new biotic index, the Foram Stress Index (FSI), is based on the relative percentages of two ecological groups of benthic foraminiferal species, grouped according to their tolerance/sensitivity to organic matter enrichment and weighted proportionately to obtain a formula to define five ecological-status classes. The FSI produced three rankings for these samples (Poor, Moderate and Good), that strongly correlate with the macroinvertebrate-classification tool known as the BENTIX Index. The FSI provides a new tool to assess sediment or substrata quality based upon the benthic foraminiferal assemblages, which are a significant component of living meiobenthic communities that are generally not considered in most biotic benthic indices.

Saronikos Gulf, including the industrial zone of Elefsis Bay and the Port of Piraeus, is one of the most anthropogenically impacted coastal regions of Greece. Distinct assemblages of benthic foraminifers in sediment samples, collected from this gulf in February 2012, defined three zones that reflect abiotic parameters of the sediments (e.g., organic carbon, metal content). A low-diversity assemblage, dominated by stress-tolerantAmmonia tepida and Bulimina spp., was characteristic of samples from Elefsis Bay. Samples from the western and central part of Saronikos Gulf were the most variable with respect to both abiotic parameters and the foraminiferal assemblage, characterized by a mix of stress-tolerant and more sensitive taxa, especially Bolivina spp. andNonion fabum. Samples from the coast of Salamis and at the eastern sector of the gulf were characterized by a diverse assemblage that included Peneroplis pertusus, miliolids, and a variety of small, epiphytic rotaliid taxa. A new biotic index, the Foram Stress Index (FSI), is based on the relative percentages of two ecological groups of benthic foraminiferal species, grouped according to their tolerance/sensitivity to organic matter enrichment and weighted proportionately to obtain a formula to define five ecological-status classes. The FSI produced three rankings for these samples (Poor, Moderate and Good), that strongly correlate with the macroinvertebrate-classification tool known as the BENTIX Index. The FSI provides a new tool to assess sediment or substrata quality based upon the benthic foraminiferal assemblages, which are a significant component of living meiobenthic communities that are generally not considered in most biotic benthic indices.

© 2016 Elsevier Ireland Ltd. Background and aims: We aimed to assess the prognostic value of free androgen index (FAI) and its change over time in arterial stiffness progression, endothelial function and hypertension in postmenopausal women. Methods: Postmenopausal women (n = 180) without clinically overt cardiovascular disease or diabetes were consecutively recruited and followed for a median of 29 months. The main outcome measures were changes over time in endothelial function (FMD), reflected waves, localized and systemic (PWV) arterial stiffness and hypertension. Results: Increased baseline FAI was significantly associated with new onset hypertension (OR for each SD, 2.71, 95% CI 1.14-6.41, p = 0.024), deterioration of pulse wave velocity (PWV) (0.414 m/s per SD), flow-mediated dilation (FMD) (-0.42% per SD), systolic (2.5 mmHg per SD) and pulse pressure progression (2.3 mmHg per SD, p < 0.05 for all). Baseline FAI remained an independent predictor of changes in PWV (p = 0.006), FMD (p = 0.02), peripheral pulse pressure (p = 0.028), transition to new onset hypertension (p = 0.001) and higher BP category (p = 0.012), after adjustment for age, changes in systolic blood pressure, traditional risk factors, vasoactive medication or total testosterone. Baseline FAI improved reclassification for the risk of transition into higher BP category (NRI = 47.5 ± 20.3%, p = 0.02) and abnormal PWV (NRI = 53.4 ± 23.2%, p = 0.021). Similarly, in a subgroup of patients with measured FAI at follow-up, its changes over time predicted changes in PWV, peripheral pulse pressure and hypertension status (p < 0.05 for all). Conclusions: In apparently healthy postmenopausal women, FAI could be a novel biomarker superior to total testosterone for accelerated vascular aging and hypertension status.

In this paper, we revisit the discovery of argon by Lord Rayleigh and William Ramsay. We argue that to understand historically how argon was detected, conceptualized, and accommodated into chemical knowledge we need to take into account the philosophical insight that scientific discovery is often an extended process. One of argon’s most intriguing properties was that it did not react with other elements. Reactivity, however, had been a constitutive property of elements. Thus, the discovery of argon could not have been accepted by chemists without a reconceptualization of ‘element’. Furthermore, there were difficulties with the accommodation of argon in the Periodic table, because argon appeared to undermine the conception of matter that underlay the Periodic table. The discovery of argon was complete only after those conceptual difficulties had been removed. This is why it has to be understood as an extended process, rather than as an event. Furthermore, we will suggest that some of the factors that complicated the discovery of argon were related to the legitimization of physical techniques of investigation in chemistry and the emergence of physical chemistry.

When citing:  Kamberidou, Irene (2016).  A Futurist and Hybrid Scientist, the result of a Multidisciplinary Education. Irene Kamberidou interviews Eleni Antoniadou, multidisciplinary scientist in Artificial Organ Technology and President of the European Health Parliament, 04/14/2016 - 12:25:  http://www.womenincomputing.eu/blog/470/futurist-and-hybrid-scientist-result-multidisciplinary-education-irene-kamberidou-ecwt    Interview for  1st European Celebration of Women in Computing (ECWC), Brussels, 25-26 April 2016! (womenincomputing.eu), organized by European European Centre for Women and Technology (ECWT): SPONSORS: http://womenincomputing.eu/sponsors Website: www.ecwt.eu

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims: A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods: The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results: Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the Hipparcos and Tycho-2 catalogues - a realisation of the Tycho-Gaia Astrometric Solution (TGAS) - and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of 3000 Cepheid and RR Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr-1 for the proper motions. A systematic component of 0.3 mas should be added to the parallax uncertainties. For the subset of 94 000 Hipparcos stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr-1. For the secondary astrometric data set, the typical uncertainty of the positions is 10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to 0.03 mag over the magnitude range 5 to 20.7. Conclusions: Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data.

Gaia is a cornerstone mission in the science programme of the EuropeanSpace Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page. http://www.cosmos.esa.int/gaia

Multiciliated cells are terminally differentiated, post-mitotic cells that form hundreds of motile cilia on their apical surface. Defects in multiciliated cells lead to disease, including mucociliary clearance disorders that result from ciliated cell disfunction in airways. The pathway controlling multiciliogenesis, however, remains poorly characterized. We showed that GemC1, previously implicated in cell cycle control, is a central regulator of ciliogenesis. GemC1 is specifically expressed in ciliated epithelia. Ectopic expression of GemC1 is sufficient to induce early steps of multiciliogenesis in airway epithelial cells ex vivo, upregulating McIdas and FoxJ1, key transcriptional regulators of multiciliogenesis. GemC1 directly transactivates the McIdas and FoxJ1 upstream regulatory sequences, and its activity is enhanced by E2F5 and inhibited by Geminin. GemC1-knockout mice are born with airway epithelia devoid of multiciliated cells. Our results identify GemC1 as an essential regulator of ciliogenesis in the airway epithelium and a candidate gene for mucociliary disorders.

The littoral region of Alexandria, east of Silsileh (the eastern promontory of the Eastern Harbor) to Montazah promontory was investigated combining archaeological and geomorphological evidence in order to better understand the subsidence of the coastal zone. The coastal zone is rich in archaeological and geomorphological features able to provide insights into the evolution of the coastline and the relative sea level changes. Our study has revealed a continuous subsidence of the coastal zone, owed to various contributing processes, while further research is required to decipher the coastal evolution of this littoral.

Women are more likely to develop depression during childbearing years with up to 20% of women suffering from depression during pregnancy and in the postpartum period. Increased prevalence of depression during the perinatal period has resulted in frequent selective serotonin reuptake inhibitor (SSRI) antidepressant treatment; however the effects of such medications on the maternal brain remain limited. Therefore, the aim of the present study is to investigate the effects of the SSRI medication, fluoxetine, on neurobiological differences in the maternal brain. To model aspects of maternal depression, gestational stress was used. Sprague-Dawley rat dams were exposed to either gestational stress and/or fluoxetine (5mg/kg/day) to form the following four groups: 1. Control+Vehicle, 2. Stress+Vehicle, 3. Control+Fluoxetine, and 4. Stress+Fluoxetine. At weaning maternal brains were collected. Main findings show that gestational stress alone increased synaptophysin and serotonin metabolism in the cingulate cortex2 region of the cortex while fluoxetine treatment after stress normalized these effects. In the hippocampus, fluoxetine treatment, regardless of gestational stress exposure, decreased both global measures of methylation in the dentate gyrus, as measured by Dnmt3a immunoreactivity, as well as serotonin metabolism. No further changes in synaptophysin, PSD-95, or Dnmt3a immunoreactivity were seen in the cortical or hippocampal areas investigated. These findings show that gestational stress and SSRI medication affect the neurobiology of the maternal brain in a region-specific manner. This work adds to a much needed area of research aimed at understanding neurobiological changes associated with maternal depression and the role of SSRI treatment in altering these changes in the female brain.

Women are more likely to develop depression during childbearing years with up to 20% of women suffering from depression during pregnancy and in the postpartum period. Increased prevalence of depression during the perinatal period has resulted in frequent selective serotonin reuptake inhibitor (SSRI) antidepressant treatment; however the effects of such medications on the maternal brain remain limited. Therefore, the aim of the present study is to investigate the effects of the SSRI medication, fluoxetine, on neurobiological differences in the maternal brain. To model aspects of maternal depression, gestational stress was used. Sprague-Dawley rat dams were exposed to either gestational stress and/or fluoxetine (5mg/kg/day) to form the following four groups: 1. Control+Vehicle, 2. Stress+Vehicle, 3. Control+Fluoxetine, and 4. Stress+Fluoxetine. At weaning maternal brains were collected. Main findings show that gestational stress alone increased synaptophysin and serotonin metabolism in the cingulate cortex2 region of the cortex while fluoxetine treatment after stress normalized these effects. In the hippocampus, fluoxetine treatment, regardless of gestational stress exposure, decreased both global measures of methylation in the dentate gyrus, as measured by Dnmt3a immunoreactivity, as well as serotonin metabolism. No further changes in synaptophysin, PSD-95, or Dnmt3a immunoreactivity were seen in the cortical or hippocampal areas investigated. These findings show that gestational stress and SSRI medication affect the neurobiology of the maternal brain in a region-specific manner. This work adds to a much needed area of research aimed at understanding neurobiological changes associated with maternal depression and the role of SSRI treatment in altering these changes in the female brain.

A concept realizing giant spin Nernst effect in nonmagnetic metallic films is introduced. It is based on the idea of engineering an asymmetric energy dependence of the longitudinal and transverse electrical conductivities, as well as a pronounced energy dependence of the spin Hall angle in the vicinity of the Fermi level by the resonant impurity states at the Fermi level. We employ an analytical model and demonstrate the emergence of a giant spin Nernst effect in Ag(111) films using ab initio calculations combined with the Boltzmann approach for transport properties arising from skew scattering off impurities.

Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood. Here we analyze a large dataset of globally representative HIV-1 subtype B strains to map their spread around the world over the last 50years and describe significant spread patterns. We show that subtype B travelled from North America to Western Europe in different occasions, while Central/Eastern Europe remained isolated for the most part of the early epidemic. Looking with more detail in European countries we see that the United Kingdom, France and Switzerland exchanged viral isolates with non-European countries than with European ones. The observed pattern is likely to mirror geopolitical landmarks in the post-World War II era, namely the rise and the fall of the Iron Curtain and the European colonialism. In conclusion, HIV-1 spread through specific migration routes which are consistent with geopolitical factors that affected human activities during the last 50years, such as migration, tourism and trade. Our findings support the argument that epidemic control policies should be global and incorporate political and socioeconomic factors.

Background: Matrix metalloproteinases (MMPs) have been implicated in the pathophysiology of various renal diseases, however, there are limited data regarding their role in renal AL-amyloidosis. In the present study, we evaluated the glomerular expression of MMPs in renal-biopsy specimens containing AL-amyloid deposits. We also examined the association of MMPs with renal function at the time of diagnostic renal biopsy. Methods: We performed immunohistochemistry with monoclonal antibodies against MMP-1, MMP-2, MMP-3, MMP-9, and TIMP-1 in 19 kidney-biopsy specimens with AL-amyloidosis and 8 specimens from normal kidney tissue. We used clinical data of the patients at the time of kidney biopsy to evaluate the association between MMP expression and renal function. Results: We found increased MMP-1 and MMP-3 expression within the amyloid deposits and adjacent tissues in > 50% of the amyloid-positive biopsies, whereas MMP-1 and MMP-3 were negative in control samples. In contrast, we found no significant glomerular MMP-2 and TIMP-1 expression in amyloid-containing or normal kidneys. MMP-9 expression was found in the glomerular basement membrane equally in AL-amyloidosis and control specimens. The presence of MMP-1 and MMP-3 in the glomeruli of patients with AL-amyloidosis correlated with worse renal function at the time of kidney biopsy. Conclusion: The findings of this study show increased glomerular expression of MMP-1 and MMP-3 in patients with AL-amyloidosis which is associated with worse renal function at the time of the kidney biopsy. Our results suggest an important role for MMP-1 and MMP-3 in the pathogenesis of renal damage in AL-amyloidosis. © 2016 Dustri-Verlag Dr. K. Feistle.

The Voices of Six Inspirational Greek Women in Sport: What inspired them to take that leap; the Obstacles they faced; how they moved forward and Tips for Success.  Many inspirational and outstanding women have made a difference in the lives of girls and women in sport, physical education (PE) and physical activity in Greece, despite their invisibility in the mainstream media, the life stories of which would need volumes. They succeeded in making a difference while respecting and celebrating diversity with regard to gender, ethnicity, culture, disability, age and sexual orientation. Beginning with a brief discussion on the underrepresentation of women’s sports and the female athlete in the Greek media, this chapter shares the contributions of some inspiring and motivating Greek women in sport whose achievements have been excluded from the country’s mainstream media. It is through six in-depth interviews and follow-up meetings that we learn how these pioneers influenced the lives of sporting girls and women by daring to disregard social barriers and spread awareness. We conclude the chapter with tips from these successful, namely inspirational women, who all agree that success requires ethos and taking that leap.http://www.ngime.ufjf.br/wp-content/uploads/Europa_opt.pdf

The coinfection of Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) has been associated with increased death rates. However, the relevant research has mostly relied on serologic HBV testing [HBV surface antigen (HBsAg)]. The aim of this work was to explore the relationship of HBV viraemia with overall mortality among HIV/HBV coinfected individuals. The analysis included 1,609 HIV seropositives of a previously described cohort (1984-2003) with limited exposure to tenofovir (12%) and a median follow-up of approximately 5 years. Those with persistent expression of HBsAg were further tested for HBV-DNA. The data were analyzed using Poisson regression models. Totally, 101 participants were chronic carriers of HBsAg (6.28%). Of these, 81 were tested for HBV-DNA. The median HBV-DNA levels were 3.81 log (base-10) International Units (IU)/ml. A third (31%) of those tested for HBV-DNA had received tenofovir. Before developing acquired immune deficiency syndrome (AIDS), the adjusted incidence rate ratio (IRR) for all-cause mortality of coinfected patients with HBV viraemia above the median value versus the HIV monoinfected group was 3.44 [95% confidence interval (CI): 1.05-11.27]. Multivariable regressions in the coinfected group only (n = 81) showed that one log-10 increase in HBV-DNA levels was associated with an elevated risk for death (IRR: 1.24, 95%CI: 1.03-1.49). HBV-DNA levels predict overall mortality in the setting of HIV/HBV coinfection, especially during the period before developing AIDS, and could thus help prioritize needs and determine the frequency of medical monitoring.

BACKGROUND: Most of the HCV transmission the recent years in Greece was among IDUs. Our aim was to estimate the prevalence of HCV genotypes and to investigate the patterns of HCV dispersal among IDUs in Athens using current state of the art molecular epidemiology methods. METHODS: HCV sequences were determined from 238 HIV-negative IDUs collected on the basis of the "ARISTOTLE" prevention program carried out in Athens between 2012 and 2013. Phylogenetic trees were inferred on HCV sequences isolated from IDUs in Athens for the most prevalent HCV clades (subtypes 1a and 3a). Phylogenetic analysis was performed by Neighbor-Joining and Bayesian methods using GTR+G as nucleotide substitution model. HCV dispersal patterns were estimated using as references, all globally available HCV sequences for subtypes 1a and 3a. RESULTS: The prevalence of HCV subtypes was: 3a (59.2%), 1a (21.9%), 4 (13.0%), 1b (5.4%) and 2 (0.5%). Phylogenetic analyses revealed that most sequences (63.5%) οf subtypes 1a and 3a fell within IDU-specific monophyletic groups. The proportion of sequences in monophyletic clades was similar for subtype 3a (62.9%) and 1a (65.3%). For the latter group, monophyletic clades were smaller in size. Multivariable logistic regression analyses showed that monophyletic clustering was marginally associated recent onset of injecting ([AOR]=1.44; 95% CI (0.97-2.13), p=0.068). CONCLUSIONS: The high proportions of HCV sequences within IDU-specific monophyletic clusters suggest that transmissions occurred locally among IDUs in Greece. The numerous clusters for both 1a and 3a provide evidence that both sub-epidemics were the result of multiple introductions among the IDUs. Higher regional clustering was probably associated with a more recent onset of drug use.

Objective:The objective of this study was to investigate the relationship between classroom psychological climate and the physical and sedentary behaviour of primary school students after the implementation of an innovative education programme regarding nutrition and physical activity.Design:Randomised controlled trial.Setting:Study participants were 729 students, aged 8?10?years, in the third and fourth grade of 30 public primary schools in the Athens Metropolitan Area.Methods:Students were randomly assigned to three study groups: an Intensive Intervention Group (IIG) that underwent an intensive nutrition and physical activity education programme delivered by specialised personnel and teachers, an Intervention Group (IG) that underwent a less intensive programme delivered by their regular teacher and a Control Group (CG) that received no instruction. Classroom Psychological Climate (CPC) was measured in all groups, and the data regarding physical activity and sedentary lifestyle habits, such as the time spent viewing TV or video games (screen time), were recorded.Results:Friction declined and satisfaction increased significantly after the intervention in the IG compared with the CG. There was no significant difference in physical activity and screen time between the groups. Daily screen time was positively associated with increased friction, which is a measure of conflicts between students in the school environment.Conclusion:A school nutrition and physical activity education programme was shown to decrease friction by decreasing daily screen time and increasing outdoor activities. These findings also suggest that teachers alone may be more effective in delivering optional health education programmes than specialised personnel and instructors.

Across-sectional survey was designed to determine health professionals' awareness and usage of online evidence retrieval systems in clinical practice. A questionnaire was used to measure professionals' behavior and utilization of online evidences, as well as, reasons and barriers on information retrieval. 439 nurses and physicians from public and private hospitals in Greece formulate the study's sample. The two most common reasons that individuals are using online information systems were for writing scientific manuscripts or filling a knowledge gap. A positive correlation was found between participants with postgraduate studies and information system usage. The majority of them (90,6%) believe that online information systems improves patient care and 67,6% of them had their own experiences on this. More support is needed to nurses and physicians in order to use the online evidence and as a result to improve the provided care and practices.

Purpose To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. Methods Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment. The Global Health Status/Quality of Life (GHS/QoL) scale and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. The percentages of responders with ≥ 5- or 15-point GHS/QoL improvement at each cycle were compared between groups. Results Baseline questionnaire compliance was excellent (94.1% of randomly assigned patients). KRd patients had higher GHS/QoL scores versus Rd patients over 18 treatment cycles (two-sided P<.001). The minimal important difference was met at cycle 12 (5.6 points) and approached at cycle 18 (4.8 points). There was no difference between groups for the other prespecified subscales from ASPIRE. A higher proportion of KRd patients met the GHS/QoL responder definition (≥ 5-point improvement) with statistical differences at cycle 12 (KRd v Rd patients, 25.5% v 17.4%, respectively) and 18 (KRd v Rd patients, 24.2% v 12.9%, respectively). Conclusion KRd improves GHS/QoL without negatively affecting patient-reported symptoms when compared with Rd. These data further support the benefit of KRd in patients with relapsed multiple myeloma. © 2016 by American Society of Clinical Oncology.

Purpose To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. Methods Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment. The Global Health Status/Quality of Life (GHS/QoL) scale and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. The percentages of responders with ≥ 5- or 15-point GHS/QoL improvement at each cycle were compared between groups. Results Baseline questionnaire compliance was excellent (94.1% of randomly assigned patients). KRd patients had higher GHS/QoL scores versus Rd patients over 18 treatment cycles (two-sided P<.001). The minimal important difference was met at cycle 12 (5.6 points) and approached at cycle 18 (4.8 points). There was no difference between groups for the other prespecified subscales from ASPIRE. A higher proportion of KRd patients met the GHS/QoL responder definition (≥ 5-point improvement) with statistical differences at cycle 12 (KRd v Rd patients, 25.5% v 17.4%, respectively) and 18 (KRd v Rd patients, 24.2% v 12.9%, respectively). Conclusion KRd improves GHS/QoL without negatively affecting patient-reported symptoms when compared with Rd. These data further support the benefit of KRd in patients with relapsed multiple myeloma. © 2016 by American Society of Clinical Oncology.

Monoclonal immunoglobulin deposition disease (MIDD) is characterized by non-organized immunoglobulin-fragments along renal basement membranes with subsequent organ deterioration. Treatment is directed against the immunoglobulin-producing clone. We treated 18 MIDD patients with bortezomib-based regimens (12 received bortezomib-dexamethasone, 6 bortezomib-dexamethasone with cyclophosphamide). Eleven (61%) patients achieved a hematologic response, but only 6 (33.3%) reached to a complete (CR) or very good partial response (VGPR). Regarding renal outcomes 77.8 and 55.6% had ≥30 and ≥50% reduction of proteinuria, respectively, but 33.3% ended up in end-stage renal disease (ESRD). Among patients with CR or VGPR, median eGFR improvement was 7.7 ml/min/1.73 m2 and none progressed to ESRD, but no significant renal recovery was observed in patients achieving a partial response or less, with 50% progressing to dialysis. Pretreatment eGFR seems to influence renal prognosis. Bortezomib-based treatment is considered an effective approach in MIDD and reaching to a deep hematologic response (≥VGPR) conditionally controls further renal declining. © 2016 Informa UK Limited, trading as Taylor & Francis Group

Monoclonal immunoglobulin deposition disease (MIDD) is characterized by non-organized immunoglobulin-fragments along renal basement membranes with subsequent organ deterioration. Treatment is directed against the immunoglobulin-producing clone. We treated 18 MIDD patients with bortezomib-based regimens (12 received bortezomib-dexamethasone, 6 bortezomib-dexamethasone with cyclophosphamide). Eleven (61%) patients achieved a hematologic response, but only 6 (33.3%) reached to a complete (CR) or very good partial response (VGPR). Regarding renal outcomes 77.8 and 55.6% had ≥30 and ≥50% reduction of proteinuria, respectively, but 33.3% ended up in end-stage renal disease (ESRD). Among patients with CR or VGPR, median eGFR improvement was 7.7 ml/min/1.73 m2 and none progressed to ESRD, but no significant renal recovery was observed in patients achieving a partial response or less, with 50% progressing to dialysis. Pretreatment eGFR seems to influence renal prognosis. Bortezomib-based treatment is considered an effective approach in MIDD and reaching to a deep hematologic response (≥VGPR) conditionally controls further renal declining. © 2016 Informa UK Limited, trading as Taylor & Francis Group

Dye solar cells (DSCs) have emerged as one of the most efficient third-generation photovoltaic (PV) technologies, whose commercialization is mainly hampered by the lack of sufficient long-term stability compared to conventional PV devices. In this work, it is demonstrated that solvent based DSCs using tetraglyme as a non-nitrile, high boiling point, organic solvent for the iodide/triiodide redox shuttle, can pass a harsh accelerated thermal ageing test of 3000 h light soaking followed by additional 2000 h thermal ageing at 85 °C. Electrochemical and spectroscopic analysis on thermal degradation effects revealed that a conduction band edge shift towards more negative potentials for tetraglyme-DSCs underlies the enhanced photopotential of aged cells, compensating for the thermally induced photocurrent reduction due to slight triiodide loss. The tetraglyme-based solar cells (in contrast to cells based on methoxypropionitrile-MPN) showed exceptional stability, compatible with the established IEC61646 protocol for thin film PVs, keeping ca. 90% of their initial performance under 1 sun illumination. Quite notably, the cells even increased their initial efficiency by 4% when illuminated under 0.1 sun. This is the first time in literature that such a stability record is accomplished for solvent based DSCs utilizing commercially available and cost-effective materials. © 2015 Elsevier B.V. All rights reserved.

This paper investigates the relationship between the volatility of Volume Synchronized Probability of Informed Trading (VPIN) and future short-term volatility of stock returns. We construct a transaction-signed version of VPIN (TR-VPIN) based on tick by tick data on securities traded in the Athens Stock Exchange (ASE) during the Greek sovereign debt crisis. The results show a positive and statistically significant correlation between the volatility of TR-VPIN and future short-term volatility for securities that are exposed to asymmetric information during the period under examination. This evidence expands the existent literature which shows that the absolute order imbalance forecasts absolute returns, suggesting that TR-VPIN is a real-time informative indicator of the Probability of Informed Trading (PIN) in the high frequency domain. Further, the long-range dependence between the conditional volatilities of TR-VPIN and stock returns becomes more significant as we move towards securities which display stronger long memory. This is perfectly in line with the recent empirical evidence in microstructure literature that large past shocks of flow toxicity can lead to volatility through liquidity shortages.

Periostin is an extracellular matrix protein that is implicated in the biology of normal bone remodeling and in different cancer cell growth and metastasis. However, there is no information on the role of periostin in multiple myeloma (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM) patients and in the serum of 23 monoclonal gammopathy of undetermined significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau phase post-first-line therapy, 30 patients at first relapse and 30 healthy controls. We found high levels of periostin in the supernatants of myeloma cell lines compared with ovarian cancer cell lines that were not influenced by the incubation with the stromal cell line HS5. In NDMM patients the bone marrow plasma periostin was almost fourfold higher compared with the serum levels of periostin and correlated with the presence of fractures and of diffuse magnetic resonance imaging pattern of marrow infiltration. Serum periostin was elevated in NDMM patients compared with healthy controls, MGUS and SMM patients and correlated with advanced disease stage, high lactate dehydrogenase, increased activin-A, increased bone resorption and reduced bone formation. Patients at first relapse had also elevated periostin compared with healthy controls, MGUS and SMM patients, while even patients at the plateau phase had elevated serum periostin compared with healthy controls. These results support an important role of periostin in the biology of myeloma and reveal periostin as a possible target for the development of antimyeloma drugs. © 2016 The Author(s).

Periostin is an extracellular matrix protein that is implicated in the biology of normal bone remodeling and in different cancer cell growth and metastasis. However, there is no information on the role of periostin in multiple myeloma (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM) patients and in the serum of 23 monoclonal gammopathy of undetermined significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau phase post-first-line therapy, 30 patients at first relapse and 30 healthy controls. We found high levels of periostin in the supernatants of myeloma cell lines compared with ovarian cancer cell lines that were not influenced by the incubation with the stromal cell line HS5. In NDMM patients the bone marrow plasma periostin was almost fourfold higher compared with the serum levels of periostin and correlated with the presence of fractures and of diffuse magnetic resonance imaging pattern of marrow infiltration. Serum periostin was elevated in NDMM patients compared with healthy controls, MGUS and SMM patients and correlated with advanced disease stage, high lactate dehydrogenase, increased activin-A, increased bone resorption and reduced bone formation. Patients at first relapse had also elevated periostin compared with healthy controls, MGUS and SMM patients, while even patients at the plateau phase had elevated serum periostin compared with healthy controls. These results support an important role of periostin in the biology of myeloma and reveal periostin as a possible target for the development of antimyeloma drugs. © 2016 The Author(s).

Combined micropaleontological and geochemical analyses of the high-sedimentation gravity core M-4G provided new centennial-scale paleoceanographic data for sapropel S1 deposition in the NE Aegean Sea during the Holocene Climatic Optimum. Sapropel layer S1a (10.2–8.0 ka) was deposited in dysoxic to oxic bottom waters characterized by a high abundance of benthic foraminiferal species tolerating surface sediment and/or pore water oxygen depletion (e.g.,Chilostomella mediterranensis, Globobulimina affinis), and the presence of Uvigerina mediterranea, which thrives in oxic mesotrophic-eutrophic environments. Preservation of organic matter (OM) is inferred based on high organic carbon as well as loliolide and isololiolide contents, while the biomarker record and the abundances of eutrophic planktonic foraminifera document enhanced productivity. High inputs of terrigenous OM are attributed to north Aegean borderland riverine inputs. Both alkenone-based sea surface temperatures (SSTs) and δO18 G. bulloides records indicate cooling at 8.2 ka (S1a) and ~7.8 ka (S1 interruption). Sapropelic layer S1b (7.7–6.4 ka) is characterized by rather oxic conditions; abundances of foraminiferal species tolerant to oxygen depletion are very low compared with the U. mediterranea rise. Strongly fluctuating SSTs demonstrate repeated cooling and associated dense water formation, with a major event at 7.4 ka followed by cold spells at 7.0, 6.8, and 6.5 ka. The prominent rise of the carbon preference index within the S1b layer indicates the delivery of less degraded terrestrial OM. The increase of algal biomarkers, labile OM-feeding foraminifera and eutrophic planktonic species pinpoints an enhanced in situ marine productivity, promoted by more efficient vertical convection due to repeated cold events. The associated contributions of labile marine OM along with fresher terrestrial OM inputs after ~7.7 ka imply sources alternative/additional to the north Aegean riverine borderland sources for the influx of organic matter in the south Limnos Basin, plausibly related to the inflow of highly productive Marmara/Black Sea waters.

Combined micropaleontological and geochemical analyses of the high-sedimentation gravity core M-4G provided new centennial-scale paleoceanographic data for sapropel S1 deposition in the NE Aegean Sea during the Holocene Climatic Optimum. Sapropel layer S1a (10.2–8.0 ka) was deposited in dysoxic to oxic bottom waters characterized by a high abundance of benthic foraminiferal species tolerating surface sediment and/or pore water oxygen depletion (e.g.,Chilostomella mediterranensis, Globobulimina affinis), and the presence of Uvigerina mediterranea, which thrives in oxic mesotrophic-eutrophic environments. Preservation of organic matter (OM) is inferred based on high organic carbon as well as loliolide and isololiolide contents, while the biomarker record and the abundances of eutrophic planktonic foraminifera document enhanced productivity. High inputs of terrigenous OM are attributed to north Aegean borderland riverine inputs. Both alkenone-based sea surface temperatures (SSTs) and δO18 G. bulloides records indicate cooling at 8.2 ka (S1a) and ~7.8 ka (S1 interruption). Sapropelic layer S1b (7.7–6.4 ka) is characterized by rather oxic conditions; abundances of foraminiferal species tolerant to oxygen depletion are very low compared with the U. mediterranea rise. Strongly fluctuating SSTs demonstrate repeated cooling and associated dense water formation, with a major event at 7.4 ka followed by cold spells at 7.0, 6.8, and 6.5 ka. The prominent rise of the carbon preference index within the S1b layer indicates the delivery of less degraded terrestrial OM. The increase of algal biomarkers, labile OM-feeding foraminifera and eutrophic planktonic species pinpoints an enhanced in situ marine productivity, promoted by more efficient vertical convection due to repeated cold events. The associated contributions of labile marine OM along with fresher terrestrial OM inputs after ~7.7 ka imply sources alternative/additional to the north Aegean riverine borderland sources for the influx of organic matter in the south Limnos Basin, plausibly related to the inflow of highly productive Marmara/Black Sea waters.

PURPOSE: During the last three decades, the number of devices that emit non-ionizing electromagnetic radiation (EMR) at the wireless communication spectrum has rapidly increased and possible effects on living organisms have become a major concern. The purpose of this study was to investigate the effects of radiofrequency EMR emitted by a widely used wireless communication device, namely the Digital Enhanced Communication Telephony (DECT) base, on the immune responses of the Aegean wall lizard (Podarcis erhardii). MATERIALS AND METHODS: Adult male lizards were exposed 24 h/day for 8 weeks to 1880-1900 MHz DECT base radiation at average electric field intensity of 3.2 V/m. Immune reactivity was assessed using the phytohemagglutinin (PHA) skin swelling and mixed lymphocyte reaction (MLR) tests. RESULTS: Our results revealed a noticeable suppression (approximately 45%) of inflammatory responses in EMR-exposed lizards compared to sham-exposed animals. T cell-mediated responses were marginally affected. CONCLUSION: Daily radiofrequency EMR exposure seems to affect, at least partially, the immunocompetence of the Aegean wall lizard.

Renal impairment is associated with poor prognosis in myeloma. This analysis of the pivotal phase 3 FIRST trial examined the impact of renally adapted dosing of lenalidomide and dexamethasone on outcomes of patients with different degrees of renal impairment. Transplant-ineligible patients not requiring dialysis were randomized 1:1:1 to receive continuous lenalidomide and dexamethasone until disease progression (n=535) or for 18 cycles (72 weeks; n=541), or melphalan, prednisone, and thalidomide for 12 cycles (72 weeks; n=547). Follow-up is ongoing. Patients were grouped by baseline creatinine clearance into no (≥ 80 mL/min [n=389]), mild (≥ 50 to < 80 mL/min [n=715]), moderate (≥ 30 to < 50 mL/min [n=372]), and severe impairment (< 30 mL/min [n=147]) subgroups. Continuous lenalidomide and dexamethasone therapy reduced the risk of progression or death in no, mild, and moderate renal impairment subgroups vs. melphalan, prednisone, and thalidomide therapy (HR = 0.67, 0.70, and 0.65, respectively). Overall survival benefits were observed with continuous lenalidomide and dexamethasone treatment vs.melphalan, prednisone, and thalidomide treatment in no or mild renal impairment subgroups. Renal function improved from baseline in 52.6% of lenalidomide and dexamethasone–treated patients. The safety profile of continuous lenalidomide and dexamethasone was consistent across renal subgroups, except for grade 3/4 anemia and rash, which increased with increasing severity of renal impairment. Continuous lenalidomide and dexamethasone treatment, with renally adapted lenalidomide dosing, was effective for most transplant-ineligible patients with myeloma and renal impairment. Trial registration: ClinicalTrials.gov (NCT00689936); EudraCT (2007- 004823-39). Funding: Intergroupe Francophone du Myélome and the Celgene Corporation. © 2016 Ferrata Storti Foundation.

{The goal of this study is to quantify the impact of airborne coarse particles between 2.5 and 80 mu m (PM2.5-PM80) on hospital admissions for respiratory diseases, acquired from the two main hospitals in Heraklion, Crete Island. The atmospheric coarse particles were collected in Heraklion city from November 18, 2011 to May 31, 2013, using the Sigma-2 passive sampler technique. Further, the Scanning Electron Microscopy (SEM), was utilized to identify the qualitative structure of PMs. On one hand, we applied Generalized Addictive Models (GAMS) in order to assess the impact of coarse particles on respiratory diseases. The findings of the analysis revealed that the highest estimates were 7.3 % (Cl: 1.00-1.01) and 7.1 % (Cl: 1.00-1.01) increases in weekly respiratory admissions associated with an increase of 10 mu g m(-3) with respect to coarse particles between 10 and 20 mu m, for men and women, respectively. On the other hand, using SEM technique, the PMs were identified by means of their chemical composition. It is worth noting the presence of Rutile (a mineral composed primarily by Titanium Dioxide), which was found in our samples with possible origin from Saharan desert, causing adverse respiratory problems.}