Biomechanical findings show that running is asymmetric in many kinetic properties. Running stiffness is a vital kinetic property of yet unknown pattern of lateralization. The aim of this study was to examine the degree and variability of lower limb dominance specific asymmetry of running in terms of leg stiffness, vertical stiffness, contact time, flight time, maximal ground reaction forceduring contact, vertical displacement of the center of mass, and change in leg length. Leg and vertical stiffness was estimated by the sine-wave method in 22 young males during treadmill runningat 4.44m/s. Lower limb dominance was determined by the triple jump test. Asymmetry was expressed as dominant – non-dominant, and indexed by the absolute asymmetry index. Significant asymmetry was found only in flight time (3.98%) and in maximal ground reaction force (1.75%). The absolute asymmetry index ranged from 1.8% to 6.4%, showed high variation between subjects (0–31.6%), and differentiated among the 7 analyzed variables. Leg and vertical stiffness in treadmill running of moderate pace (4.44 m/s) should be considered symmetric.
Consecutive patients that had primary metal-on-metal (MoM) or metal-on-polyethylene (MoP) hip arthroplasty were prospectively enrolled to this study. All operated hips were evaluated with MRI by one radiologist who was blinded to the radiographic findings and clinical symptoms. Three groups of patients were formed: (1) thirteen MoM THRs in 13 patients with groin pain (Group 1), (2) ten MoM THRs in 10 patients with no pain (Group 2), (3) five MoP THRs in 4 patients without pain (control group). Abnormal MRI findings were distributed in all groups in a balanced way, irrespective of the patients' symptoms, prostheses, or metal ion levels. Two patients from Group 1 and one patient of Group 3 (control group) were diagnosed with a large periprosthetic mass (pseudotumor).
Multiciliated cells are abundant in the epithelial surface of different tissues, including cells lining the walls of the lateral ventricles in the brain and the airway epithelium. Their main role is to control fluid flow and defects in their differentiation are implicated in many human disorders, such as hydrocephalus, accompanied by defects in adult neurogenesis and mucociliary disorder in the airway system. Here we show that Mcidas, which is mutated in human mucociliary clearance disorder, and GemC1 (Gmnc or Lynkeas), previously implicated in cell cycle progression, are key regulators of multiciliated ependymal cell generation in the mouse brain. Overexpression and knockdown experiments show that Mcidas and GemC1 are sufficient and necessary for cell fate commitment and differentiation of radial glial cells to multiciliated ependymal cells. Furthermore, we show that GemC1 and Mcidas operate in hierarchical order, upstream of Foxj1 and c-Myb transcription factors, which are known regulators of ependymal cell generation, and that Notch signaling inhibits GemC1 and Mcidas function. Our results suggest that Mcidas and GemC1 are key players in the generation of multiciliated ependymal cells of the adult neurogenic niche.
The assessment of dietary attitudes and behaviors provides information of interest to sports nutritionists. Although there has been little analysis of the quality of research undertaken in this field, there is evidence of a number of flaws and methodological concerns in some of the studies in the available literature. This review undertook a systematic assessment of the attributes of research assessing the nutritional knowledge and attitudes of athletes and coaches. Sixty questionnaire-based studies were identified by a search of official databases using specific key terms with subsequent analysis by certain inclusion–exclusion criteria. These studies were then analyzed using 33 research quality criteria related to the methods, questionnaires, and statistics used. We found that many studies did not provide information on critical issues such as research hypotheses (92%), the gaining of ethics approval (50%) or informed consent (35%), or acknowledgment of limitations in the implementation of studies or interpretation of data (72%). Many of the samples were non-probabilistic (85%) and rather small (42%). Many questionnaires were of unknown origin (30%), validity (72%), and reliability (70%) and resulted in low (≤ 60%) response rates (38%). Pilot testing was not undertaken in 67% of the studies. Few studies dealt with sample size (2%), power (3%), assumptions (7%), confidence intervals (3%), or effect sizes (3%). Improving some of these problems and deficits may enhance future research in this field.
In the case of pediatric medicinal products the selection of an appropriate and palatable liquid dosage form can make the difference between treatment success and failure. Since the recent adoption of Pediatric Regulations in the U.S. and E.U., there is a greater demand for age-appropriate medicines for children. Extended research on the use of milk on drug administration in pediatric population has shown the multiple benefits of its use. Milk exhibits great solubilizing, gastroprotective and taste masking properties, which are very important characteristics in the case of insoluble, irritating and bitter-tasting active compounds. Milk-based formulations rely on a novel, simple and user-friendly approach for the delivery of ionized and unionized lipophilic drugs. In parallel they can provide critical nutritive elements and a wide range of biologically active peptides, very important elements especially for pediatric patients. (C) 2015 Elsevier B.V. All rights reserved.
Mitochondria represent the major bioenergetic hub coordinating cellular and organismal homeostasis. The underlying causes of many pathologies tormenting humans converge on impaired mitochondrial maintenance. Mitochondria-specific autophagy (mitophagy), a cellular catabolic process targeting mitochondria, holds a prominent role in mitochondrial quality control. In addition to core autophagic machinery components, mitophagy exploits a variety of molecules that identify damaged or superfluous mitochondria and mediate their elimination. Signaling pathways integrating environmental and genetic stimuli interact with key mitophagy effectors to activate cellular stress response mechanisms, ultimately modulating health and lifespan. Here, we review the signaling cascades and molecular mechanisms that govern the process of mitophagy and discuss their involvement in ageing and neurodegeneration. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging.
Molecular typing data on antimicrobial-resistant Propionibacterium strains are limited in the literature. We examined antimicrobial resistance profiles and the underlying resistance mechanisms in Propionibacterium spp. isolates recovered from patients with moderate to severe acne vulgaris in Greece. The clonallity of the resistant Propionibacterium acnes isolates was also investigated. Propionibacterium spp. isolates were detected using Tryptone-Yeast Extract-Glucose (TYG) agar plates supplemented with 4% furazolidone. Erythromycin, clindamycin, vancomycin, penicillin, co-trimoxazole, doxycycline, minocycline and ciprofloxacin MICs were determined using the gradient strip method. Erythromycin, clindamycin and tetracycline mechanisms of resistance were determined using PCR and sequencing of the domain V of 23S rRNA and 16S rRNA, as well as the presence of the ermX gene. Typing was performed using the multi locus sequence typing (MLST) methodology. Seventy nine isolates from 76 patients were collected. Twenty-three isolates (29.1%) exhibited resistance to erythromycin and clindamycin, while two additional isolates (2.5%) were resistant only to erythromycin. Resistance to tetracycline was not detected. The underlying molecular mechanisms were point mutations A2059G and A2058G. MLST typing of the P. acnes resistant isolates revealed that lineage type IA1 (ST-1, 3 and 52) prevailed (12/18; 66.7%), whilst lineage type IA2 (ST-2 and 22) accounted for five more isolates (27.8%). Susceptible isolates were more evenly distributed between ST types. Propionibacterium spp. from moderate to severe acne vulgaris in Greece are frequently resistant to erythromycin/clindamycin but not to tetracyclines, mainly due to the point mutations A2059G and A2058G. P. acnes resistant isolates were more clonally related than susceptible ones and belonged to a limited number of MLST types.
BACKGROUND: HIV-1 subtype B is the predominant one in European regions several, while other subtypes and recombinants are also circulating with high prevalence. A sub-epidemic of subtype F with specific characteristics and low response to treatment has been recently identified in Galicia. In this study we investigated the characteristics of the HIV-1 subtype F sub-epidemic in A Coruña and Santiago de Compostela in Northwest Spain.
METHODS: 420 newly HIV-1 diagnosed patients during 2009-2013 were enrolled in this study. HIV-1 subtyping was carried out using automated subtyping tools and phylogenetic analysis. Molecular epidemiology investigation of subtypes B and F was performed by means of phylogenetic analysis using fast maximum likelihood. Phylodynamic analysis was performed using Bayesian method as implemented in BEAST v1.8.
RESULTS: Subtype B found to be the predominant (61.2% and 70.4%) followed by subtype F (25.6% and 12.0%) in both areas (A Coruña and Santiago de Compostela, respectively). The latter found to mainly spread among men having sex with men (MSM). The vast majority of subtype F lineages from both areas clustered monophyletically, while subtype B sequences clustered in several tree branches. The exponential growth of subtype F sub-epidemic dated back in 2008 by means of phylodynamic analysis. Most of new infections during 2009-2013 occurred within the subtype F transmission cluster.
CONCLUSIONS: Subtype F circulates at high prevalence in A Coruña and Santiago de Compostela in Northwest Spain, suggesting that the HIV-1 epidemic in this region has distinct characteristics to the rest of Spain. Subtype F has being spreading among MSM and is currently the most actively spreading network. The single cluster spread of this local sub-epidemic might provide an explanation for the distinct characteristics and the low response to antiretroviral treatment.
Muscle LIM Protein (MLP) has emerged as a key regulator of striated muscle physiology and pathophysiology. Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, are causative of human cardiomyopathies, whereas altered expression patterns are observed in human failing heart and skeletal myopathies. In vitro and in vivo evidences reveal a complex and diverse functional role of MLP in striated muscle, which is determined by its multiple interacting partners and subcellular distribution. Experimental evidence suggests that MLP is implicated in both myogenic differentiation and myocyte cytoarchitecture, although the full spectrum of its intracellular roles still unfolds.
The aim of the study was to compare the effects of compound vs. complex resistance training on strength, high-speed movement performance, and muscle composition. Eighteen young men completed compound (strength and power sessions on alternate days) or complex training (strength and power sets within a single session) 3 times per week for 6 weeks using bench press, leg press, Smith machine box squat, and jumping exercises. Pre- and posttraining, jumping and throwing performance and maximum bench press, leg press, and Smith machine box squat strength were evaluated. The architecture of vastus lateralis and gastrocnemius muscle was assessed using ultrasound imaging. Vastus lateralis morphology was assessed from muscle biopsies. Jumping (4 ± 3%) and throwing (9 ± 8%) performance increased only with compound training (p < 0.02). Bench press (5 vs. 18%), leg press (17 vs. 28%), and Smith machine box squat (27 vs. 35%) strength increased after both compound and complex training. Vastus lateralis thickness and fascicle angle and gastrocnemius fascicle angle were increased with both compound and complex training. Gastrocnemius fascicle length decreased only after complex training (-11.8 ± 9.4%, p = 0.006). Muscle fiber cross-sectional areas increased only after complex training (p ≤ 0.05). Fiber type composition was not affected by either intervention. These results suggest that short-term strength and power training on alternate days is more effective for enhancing lower-limb and whole-body power, whereas training on the same day may induce greater increases in strength and fiber hypertrophy.
BACKGROUND: There is sparse evidence that demonstrates the association between macro-environmental processes and drug-related HIV epidemics. The present study explores the relationship between economic, socio-economic, policy and structural indicators, and increases in reported HIV infections among people who inject drugs (PWID) in the European Economic Area (EEA). METHODS: We used panel data (2003-2012) for 30 EEA countries. Statistical analyses included logistic regression models. The dependent variable was taking value 1 if there was an outbreak (significant increase in the national rate of HIV diagnoses in PWID) and 0 otherwise. Explanatory variables included the growth rate of Gross Domestic Product (GDP), the share of the population that is at risk for poverty, the unemployment rate, the Eurostat S80/S20 ratio, the Gini coefficient, the per capita government expenditure on health and social protection, and variables on drug control policy and drug-using population sizes. Lags of one to three years were investigated. FINDINGS: In multivariable analyses, using two-year lagged values, we found that a 1% increase of GDP was associated with approximately 30% reduction in the odds of an HIV outbreak. In GDP-adjusted analyses with three-year lagged values, the effect of the national income inequality on the likelihood of an HIV outbreak was significant [S80/S20 Odds Ratio (OR) = 3.89; 95% Confidence Interval (CI): 1.15 to 13.13]. Generally, the multivariable analyses produced similar results across three time lags tested. INTERPRETATION: Given the limitations of ecological research, we found that declining economic growth and increasing national income inequality were associated with an elevated probability of a large increase in the number of HIV diagnoses among PWID in EEA countries during the last decade. HIV prevention may be more effective if developed within national and European-level policy contexts that promote income equality, especially among vulnerable groups.
BACKGROUND: There is sparse evidence that demonstrates the association between macro-environmental processes and drug-related HIV epidemics. The present study explores the relationship between economic, socio-economic, policy and structural indicators, and increases in reported HIV infections among people who inject drugs (PWID) in the European Economic Area (EEA).
METHODS: We used panel data (2003-2012) for 30 EEA countries. Statistical analyses included logistic regression models. The dependent variable was taking value 1 if there was an outbreak (significant increase in the national rate of HIV diagnoses in PWID) and 0 otherwise. Explanatory variables included the growth rate of Gross Domestic Product (GDP), the share of the population that is at risk for poverty, the unemployment rate, the Eurostat S80/S20 ratio, the Gini coefficient, the per capita government expenditure on health and social protection, and variables on drug control policy and drug-using population sizes. Lags of one to three years were investigated.
FINDINGS: In multivariable analyses, using two-year lagged values, we found that a 1% increase of GDP was associated with approximately 30% reduction in the odds of an HIV outbreak. In GDP-adjusted analyses with three-year lagged values, the effect of the national income inequality on the likelihood of an HIV outbreak was significant [S80/S20 Odds Ratio (OR) = 3.89; 95% Confidence Interval (CI): 1.15 to 13.13]. Generally, the multivariable analyses produced similar results across three time lags tested.
INTERPRETATION: Given the limitations of ecological research, we found that declining economic growth and increasing national income inequality were associated with an elevated probability of a large increase in the number of HIV diagnoses among PWID in EEA countries during the last decade. HIV prevention may be more effective if developed within national and European-level policy contexts that promote income equality, especially among vulnerable groups.
BACKGROUND: Greece experienced an unprecedented increase in HIV cases among drug injectors in 2011 after economic crisis. Network-level factors are increasingly understood to drive HIV transmission in emerging epidemics.
METHODS: We examined the relationship between networks, risk behaviors, and HIV serostatus among 1404 people who inject drugs in Athens, Greece. We generated networks using the chain-referral structure within a large HIV screening program. Network proportions, the proportion of a respondent's network with a given characteristic, were calculated. Multiple logistic regression models were used to assess the relationship between network proportions and individual HIV seroprevalence, injection frequency and unprotected sex.
RESULTS: Of note, 1030 networks were generated. Respondent HIV seroprevalence was associated with greater proportions of network members who were HIV infected (ie, those with ≥ 50% of network members HIV positive vs. those with no network members HIV positive) (AOR: 3.11; 95% CI: 2.10 to 4.62), divided drugs (AOR: 1.60; 95% CI: 1.10 to 2.35), or injected frequently (AOR: 1.50; 95% CI: 1.02 to 2.21). Homelessness was the only sociodemographic characteristic associated with a risk outcome measure--high-frequency injecting (AOR: 1.41; 95% CI: 1.03 to 1.93). These associations were weaker for more distal second- and third-degree networks and not present when examined within random networks.
CONCLUSIONS: Networks are an independently important contributor to the HIV outbreak in Athens, Greece. Network associations were strongest for the immediate network, with residual associations for distal networks. Homelessness was associated with high-frequency injecting. Prevention programs should consider including network-level interventions to prevent future emerging epidemics.
BACKGROUND: Greece experienced an unprecedented increase in HIV cases among drug injectors in 2011 after economic crisis. Network-level factors are increasingly understood to drive HIV transmission in emerging epidemics. METHODS: We examined the relationship between networks, risk behaviors, and HIV serostatus among 1404 people who inject drugs in Athens, Greece. We generated networks using the chain-referral structure within a large HIV screening program. Network proportions, the proportion of a respondent's network with a given characteristic, were calculated. Multiple logistic regression models were used to assess the relationship between network proportions and individual HIV seroprevalence, injection frequency and unprotected sex. RESULTS: Of note, 1030 networks were generated. Respondent HIV seroprevalence was associated with greater proportions of network members who were HIV infected (ie, those with >/= 50% of network members HIV positive vs. those with no network members HIV positive) (AOR: 3.11; 95% CI: 2.10 to 4.62), divided drugs (AOR: 1.60; 95% CI: 1.10 to 2.35), or injected frequently (AOR: 1.50; 95% CI: 1.02 to 2.21). Homelessness was the only sociodemographic characteristic associated with a risk outcome measure--high-frequency injecting (AOR: 1.41; 95% CI: 1.03 to 1.93). These associations were weaker for more distal second- and third-degree networks and not present when examined within random networks. CONCLUSIONS: Networks are an independently important contributor to the HIV outbreak in Athens, Greece. Network associations were strongest for the immediate network, with residual associations for distal networks. Homelessness was associated with high-frequency injecting. Prevention programs should consider including network-level interventions to prevent future emerging epidemics.
The purpose of our study was to summarize all the knowledge concerning the innovative pioneer in the field of orthopaedic surgery, Nicholas J. Giannestras (1908-1978). A thorough study of texts, medical books and reports, in the field of history of medicine, together with a review of the available literature in PubMed, was undertaken. Giannestras left his mark in the history of orthopaedics with his clinical work and his publications, mainly his treatise "Foot Disorders: Medical and Surgical Management" (1973), while his name lingers in Greece with the introduction of spine fusion with the use of metallic implants. He was an eminent university clinical professor of orthopaedics who had harmonically combined academic writing, teaching and clinical research in every field of orthopaedic surgery.
BACKGROUND: Age-related macular degeneration (AMD) is a degenerative ocular disease, which may lead to loss of central vision. In Caucasian populations, a strong correlation has been established with polymorphism Y402H (rs1061170) in the complement factor H gene (CFH). The H131R polymorphism (rs1801274) in the FCGR2A gene has been associated with many inflammatory diseases, but has not been investigated in relation to AMD. The goal of our study was the development of a novel method for Y402H (g.43097C>T) genotyping, the confirmation of its association with AMD in the Greek population and the investigation of the H131R polymorphism in AMD. METHODS: DNAs were extracted from blood samples of 120 patients with the severe wet form of AMD and 103 age- and sex-matched controls, all of whom were clinically evaluated. A real-time PCR and melting curve analysis method for Y402H genotyping was developed in the LightCycler platform, after in silico design of appropriate primers and probes. Genotyping for H131R was performed using a real-time PCR method previously described by our group. RESULTS: The novel genotyping method for Y402H in the CFH gene is fast, reproducible (Efficiency=1.79, reproducibility CVCq=3.33%, Tm C allele 53.36 degrees C and T allele 61.91 degrees C, DeltaTm=8.55) and accurate as results were confirmed with the gold standard DNA Sequencing method. CONCLUSIONS: The present study confirmed the association between CFH Y402H SNP and wet AMD in the Greek population (OR=1.77, p=0.002). FCGR2A H131R polymorphism was investigated for the first time in this present study for possible correlation with wet AMD and a statistically significant association was detected (OR=1.74, p=0.006), that awaits further confirmation in a larger set of samples
Valid characterization of carotid atherosclerosis (CA) is a crucial public health issue, which would limit the major risks held by CA for both patient safety and state economies. This paper investigated the unexplored potential of kinematic features in assisting the diagnostic decision for CA in the framework of a computer-aided diagnosis (CAD) tool. To this end, 15 CAD schemes were designed and were fed with a wide variety of kinematic features of the atherosclerotic plaque and the arterial wall adjacent to the plaque for 56 patients from two different hospitals. The CAD schemes were benchmarked in terms of their ability to discriminate between symptomatic and asymptomatic patients and the combination of the Fisher discriminant ratio, as a feature-selection strategy, and support vector machines, in the classification module, was revealed as the optimal motion-based CAD tool. The particular CAD tool was evaluated with several cross-validation strategies and yielded higher than 88% classification accuracy; the texture-based CAD performance in the same dataset was 80%. The incorporation of kinematic features of the arterial wall in CAD seems to have a particularly favorable impact on the performance of image-data-driven diagnosis for CA, which remains to be further elucidated in future prospective studies on large datasets.
abstract extra virgin olive oil contains significant quantities of polar phenolic ingredients. The large majority is made up of esters of tyrosol or hydroxytyrosol with secoiridoid derivatives from oleuropein or ligstroside. in the current study we describe a number of new or incompletely characterized forms of ligstroside and oleuropein aglycons. two of them which are stable enolic forms are described for the first time as real olive oil ingredients although their presence in olive oil had been postulated. to minimize the confusion with the complicated names of the agly-con isomers we propose the names oleokoronal and oleomissional for the two ingredients. after screening 2000 samples of olive oil from most major varieties we were able to identify samples of olive oil in which oleokoronal and oleomissional were the major phenolic ingredients and could be used as starting material for their isolation. interestingly, during normal or reversed phase chromatography both compounds were transformed to the known forms of monoaldehydic closed ring aglycons, which offers an explanation as to why those compounds had not been identified so far. Their real presence in olive oil was confirmed by direct nMr observation without the use of any solvent.
abstract extra virgin olive oil contains significant quantities of polar phenolic ingredients. The large majority is made up of esters of tyrosol or hydroxytyrosol with secoiridoid derivatives from oleuropein or ligstroside. in the current study we describe a number of new or incompletely characterized forms of ligstroside and oleuropein aglycons. two of them which are stable enolic forms are described for the first time as real olive oil ingredients although their presence in olive oil had been postulated. to minimize the confusion with the complicated names of the agly-con isomers we propose the names oleokoronal and oleomissional for the two ingredients. after screening 2000 samples of olive oil from most major varieties we were able to identify samples of olive oil in which oleokoronal and oleomissional were the major phenolic ingredients and could be used as starting material for their isolation. interestingly, during normal or reversed phase chromatography both compounds were transformed to the known forms of monoaldehydic closed ring aglycons, which offers an explanation as to why those compounds had not been identified so far. Their real presence in olive oil was confirmed by direct nMr observation without the use of any solvent.
Central to the process of transmembrane cargo trafficking is the successful folding and exit from the ER through packaging in COPII vesicles. Here, we use the UapA purine transporter of Aspergillus nidulans to investigate the role of cargo oligomerization in membrane trafficking. We show that UapA oligomerizes (at least dimerizes) and that oligomerization persists upon UapA endocytosis and vacuolar sorting. Using a validated BiFC assay, we provide evidence that a UapA oligomerization is associated with ER exit and turnover, as ER-retained mutants, either due to modification of a Tyr-based N-terminal motif or partial misfolding, physically associate, but do not associate properly. Co-expression of ER-retained mutants with wild-type UapA leads to in trans plasma membrane localization of the former, confirming that oligomerization initiates in the ER. Genetic suppression of an N-terminal mutation in the Tyr motif and mutational analysis suggest that transmembrane α-helix 7 affects the oligomerization interface. Our results reveal that transporter oligomerization is essential for membrane trafficking and turnover and is a common theme in fungi and mammalian cells.
BACKGROUND: Atherosclerotic lesions at the origin of common carotid, subclavian, and innominate arteries are causes for brain and hand ischemic symptoms. Surgical reconstructions of symptomatic cases remain the golden standard treatment, although the endovascular approach has been promising as well. In this retrospective study, long-term results of open reconstructions from 2 University Hospitals are presented.
METHODS: Through a 30-year period, prospective data of 107 patients, suffering from symptomatic atherosclerotic supra-aortic artery disease, were retrospectively reviewed and included in this study. Demographic data, arterial risk factors, presenting symptoms and signs, diagnostic evaluation, operative treatment and complications, resolution of symptoms, redo surgery, and overall mortality were analyzed.
RESULTS: Eighty-one patients were operated on for subclavian, 14 for innominate, and 12 for common carotid severe lesions, through an extra-thoracic reconstruction (91 patients) or a transthoracic one (16 patients). Perioperative mortality was null although morbidity was 16.8%, and primary perioperative patency was 97.2% (secondary patency 100%). The cumulative primary patency was 95.3%, 90.7%, and 86.0% at 5, 10, and 15 years, respectively. The mean time of patency was 214.6 months (95% confidence interval = 198.5-230.6), with no difference between transthoracic and extrathoracic reconstructions (P = 0.278).
CONCLUSIONS: Open reconstructions remain a therapeutic strategy with a considerably low perioperative morbidity/mortality offering excellent long-term results regarding patency of the reconstructions and clinical resolution of the symptoms. However, in the modern era of the endovascular techniques, we need more studies for establishing anatomic and clinical criteria regarding patient selection for endovascular angioplasty/stenting or open repair.
V404 Cyg is a known black hole Low mass X-ray binary with a late G-type companion, having a ~6.5 d orbital period. On June 15 18:32 UT Swift Burst Alert Telescope (BAT) was triggered due to the high X-ray activity of the system (Barthelmy et al.
A puzzling, slightly submerged, single tidal notch has been reported from the carbonate coasts of the northeastern Adriatic Sea. This paper attempts to explain the origin and the recent evolution of this marine erosion feature and the reasons for its uniqueness in the late Holocene. After reviewing how tidal notches are usually formed, a comparison of recent measurements of bioerosion rates carried out in the area show that when the contribution of dissolution processes can be neglected, bioerosion rates of the deepening of tidal-notch profiles appear to be very low (often <0.1 mm/y) along the coasts of Istria, in contrast to higher rates (between 0.2 and 1.0 mm/y) generally reported in other Mediterranean areas. Such a low rate of bioerosion implies a long period favourable to tidal-notch development. Several glacial isostatic adjustment computations show that relative sea level changes in the area during the last few millennia may correspond to a period of equilibrium between the regional tectonic subsidence and hydro-isostatic emergence during which relative sea level changes were limited, permitting development of the tidal notch observed. The submergence of the notch is consistent with a coseismic subsidence in late Roman time. After this, a new tidal notch could not form at the present sea level because of the limited amount of local bioerosion and the relatively large rate of sea level rise.
NCS1 proteins are H(+) /Na(+) symporters specific for the uptake of purines, pyrimidines and related metabolites. In this article we study the origin, diversification and substrate specificity of fungal NCS1 transporters. We show that the two fungal NCS1 subfamilies, Fur and Fcy, and plant homologues, originate through independent horizontal transfers from prokaryotes, and that expansion by gene duplication led to the functional diversification of fungal NCS1. We characterized all Fur proteins of the model fungus Aspergillus nidulans and discovered novel functions and specificities. Homology modelling, substrate docking, molecular dynamics and systematic mutational analysis in three Fur transporters with distinct specificities identified residues critical for function and specificity, located within a major substrate binding site, in transmembrane segments TMS1, TMS3, TMS6 and TMS8. Most importantly, we predict and confirm that residues determining substrate specificity are located not only in the major substrate binding site, but also in a putative outward-facing selective gate. Our evolutionary and structure-function analysis contributes in the understanding of the molecular mechanisms underlying the functional diversification of eukaryotic NCS1 transporters, and in particular, forward the concept that selective channel-like gates might contribute to substrate specificity.
Bone metabolism has not been systematically studied in primary (AL) amyloidosis. Thus we prospectively evaluated bone remodeling indices in 102 patients with newly diagnosed AL amyloidosis, 35 healthy controls, 35 newly diagnosed myeloma and 40 monoclonal gammopathy of undetermined significance patients. Bone resorption markers (C-telopeptide of type-1 collagen, N-telopeptide of type-1 collagen) and osteoclast regulators (soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG)) were increased in AL patients compared with controls (P<0.01), but bone formation was unaffected. Myeloma patients had increased bone resorption and decreased bone formation compared with AL patients, while sRANKL/OPG ratio was markedly decreased in AL, due to elevated OPG in AL (P<0.001). OPG correlated with N-terminal pro-brain natriuretic peptide (P<0.001) and was higher in patients with cardiac involvement (P=0.028) and advanced Mayo stage (P=0.001). OPG levels above the upper value of healthy controls was associated with shorter survival (34 versus 91 months; P=0.026), while AL patients with OPG levels in the top quartile had very short survival (12 versus 58 months; P=0.024). In Mayo stage 1 disease, OPG identified patients with poor survival (12 versus >60 months; P=0.012). We conclude that increased OPG in AL is not only a compensation to osteoclast activation but may also reflect early cardiac damage and may identify patients at increased risk of death within those with earlier Mayo stage.
Bone metabolism has not been systematically studied in primary (AL) amyloidosis. Thus we prospectively evaluated bone remodeling indices in 102 patients with newly diagnosed AL amyloidosis, 35 healthy controls, 35 newly diagnosed myeloma and 40 monoclonal gammopathy of undetermined significance patients. Bone resorption markers (C-telopeptide of type-1 collagen, N-telopeptide of type-1 collagen) and osteoclast regulators (soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG)) were increased in AL patients compared with controls (P<0.01), but bone formation was unaffected. Myeloma patients had increased bone resorption and decreased bone formation compared with AL patients, while sRANKL/OPG ratio was markedly decreased in AL, due to elevated OPG in AL (P<0.001). OPG correlated with N-terminal pro-brain natriuretic peptide (P<0.001) and was higher in patients with cardiac involvement (P = 0.028) and advanced Mayo stage (P = 0.001). OPG levels above the upper value of healthy controls was associated with shorter survival (34 versus 91 months; P = 0.026), while AL patients with OPG levels in the top quartile had very short survival (12 versus 58 months; P = 0.024). In Mayo stage 1 disease, OPG identified patients with poor survival (12 versus 460 months; P = 0.012). We conclude that increased OPG in AL is not only a compensation to osteoclast activation but may also reflect early cardiac damage and may identify patients at increased risk of death within those with earlier Mayo stage.
INTRODUCTION: Heart failure (HF) treatment attracts a share of intensive research because of its poor HF prognosis. In the past decades, the prognosis of HF has improved considerably, mainly as a consequence of the progress that has been made in the pharmacological management of HF. AREAS COVERED: This article reviews the outpatient pharmacological management of chronic HF due to left ventricular systolic dysfunction and offers recommendations on the use of various drugs. In addition, the present article attempts to provide practical therapeutic algorithms based on current clinical strategies. EXPERT OPINION: Continued research directed toward identifying factors associated with high pharmacotherapy guideline adherence and understanding of variants that influence response to drugs will hopefully halt or reverse the major pathophysiological mechanisms involved in this syndrome.
PURPOSE: The identification of childhood acute lymphoblastic leukemia (ch-ALL) patients who are at a higher risk of chemotherapy resistance and relapse is essential for successful treatment decisions, despite the application of novel therapies. The aim of the study is the evaluation of BCL2 and BAX expression for the prognosis of ch-ALL patients treated with Berlin-Frankfurt-Munster (BFM) backbone protocol. METHODS: Bone marrow specimens were obtained at the time of diagnosis and on day 33 following BFM treatment induction from 82 ch-ALL patients, as well as from 63 healthy children. Following extraction, total RNA was reverse transcribed and BCL2 and BAX expression levels were determined by qPCR. RESULTS: BCL2 expression and BCL2/BAX ratio were strongly upregulated in ch-ALL compared to healthy children and were correlated with favorable prognostic disease features. Increased levels of BCL2 and BAX expression were associated with disease remission, as ch-ALL patients with lower expression ran a significantly higher risk of M2-M3 response, positive MRD and poor survival outcome. Moreover, the upregulation of BCL2 and BAX following BFM treatment induction was shown to represent an independent predictor of patients' short-term relapse, which was further confirmed in ch-ALL patients with favorable prognostic markers. CONCLUSIONS: In conclusion, BCL2 and BAX could be effectively used for an enhanced prediction of BFM-treated patients' outcome.
Oxidative stress refers to cellular or molecular damage caused by reactive oxygen species, which especially occurs in age-related conditions as a result of an imbalance between the production of reactive oxygen species and the antioxidant defense response. Dry age-related macular degeneration (AMD) and exfoliation syndrome (XFS) are two common and complex age-related conditions that can cause irreversible vision loss. Two subtypes of AMD, which is the leading cause of blindness in the Western world, exist: the most prevalent dry type and the most severe wet type. Early dry AMD is characterized by formation of drusen, which are sub-retinal deposits, in the macular area and may progress to geographic atrophy with more dramatic manifestation. XFS is a systemic disorder of the extracellular matrix characterized by the accumulation of elastic fibrils that leads, in most cases, to glaucoma development with progressive and irreversible vision loss. Due to the aging population, the prevalence of these already-widespread conditions is increasing and is resulting in significant economic and psychological costs for individuals and for society. The exact composition of the abnormal drusen and XFS material as well as the mechanisms responsible for their production and accumulation still remain elusive, and consequently treatment for both diseases is lacking. However, recent epidemiologic, genetic and molecular studies support a major role for oxidative stress in both dry AMD and XFS development. Understanding the early molecular events in their pathogenesis and the exact role of oxidative stress may provide novel opportunities for therapeutic intervention for the prevention of progression to advanced disease
Colette A, Andersson C, Baklanov A, Bessagnet B, Brandt J, Christensen JH, Doherty R, Engardt M, Geels C, Giannakopoulos C, et al.Is the ozone climate penalty robust in Europe?. Environmental Research Letters [Internet]. 2015;10. Website
Insulinomas are rare pancreatic neuroendocrine tumors that are most commonly benign, solitary, and intrapancreatic. Uncontrolled insulin overproduction from the tumor produces neurological and adrenergic symptoms of hypoglycemia. Biochemical diagnosis is confirmed by the presence of Whipple's triad, along with corroborating measurements of blood glucose, insulin, proinsulin, C-peptide, β-hydroxybutyrate, and negative tests for hypoglycemic agents during a supervised fasting period. This is accompanied by accurate preoperative localization using both invasive and non-invasive imaging modalities. Following this, careful preoperative planning is required, with the ensuing procedure being preferably carried out laparoscopically. An integral part of the laparoscopic approach is the application of laparoscopic intraoperative ultrasound, which is indispensable for accurate intraoperative localization of the lesion in the pancreatic region. The extent of laparoscopic resection is dependent on preoperative and intraoperative findings, but most commonly involves tumor enucleation or distal pancreatectomy. When performed in an experienced surgical unit, laparoscopic resection is associated with minimal mortality and excellent long-term cure rates. Furthermore, this approach confers equivalent safety and efficacy rates to open resection, while improving cosmesis and reducing hospital stay. As such, laparoscopic resection should be considered in all cases of benign insulinoma where adequate surgical expertise is available.
BACKGROUND: Besides the vast success and reliability of lower extremity joint replacement, deep and periprosthetic infection remains a serious complication of such operations. Many publications addressing periprosthetic infection have remarked about this "devastating" complication, with a risk around 1% after total hip arthroplasty and between 1% and 2% after total knee arthroplasty. The purpose of this study is to assess current trends in prevention of contamination with improved up-to-date pre-operative skin preparation methods and intra-operative draping.
METHODS: A literature review was conducted in MEDLINE, Web of Science, and the Cochrane database, looking for high-quality papers summarizing the most widely held and up-to-date concepts of perioperative measures for reducing infection, focusing on the best available evidence concerning skin preparation for joint arthroplasty (THR and THR) and surgical draping.
RESULTS: Current evidence suggests the use of alcohol solutions for pre-operative painting with emphasis on the use of chlorhexidine gluconate solutions beginning the night before surgery. Hair removal should be performed in the operating room with electric clippers, not razor blades. In order to enhance drape adhesion to the skin, the use of iodophor-in-alcohol solutions is recommended over the traditional scrub-and-paint technique. Disposable non-woven drapes are superior to reusable woven cotton/linen drapes in resisting bacterial penetration. Finally, the use of adherent plastic adhesive incision drapes for the prophylaxis of post-operative surgical site infections is considered not necessary in orthopedic surgery.
CONCLUSIONS: The importance of skin preparation and adequate and reliable draping cannot be overemphasized for infection prevention, especially in clean operations such as THR and TKR. Thorough and strict protocols are mandatory for every department, as well as education curricula for operating room personnel. Further randomized studies are mandatory to specify the effect of the above measures, their pitfalls, and their improvement, along with further crucial details such as cost-benefit analysis of different pre-operative preparations in preventing infections.
A publicity campaign run in Athens by the Alexander S. Onassis Public Benefit Foundation in October 2013 in order to advertise its acquisition of the Cavafy Archive, until then lying in relevant obscurity, turned into a media disaster when critics and members of the public protested against what they argued was a misquoting of the highly revered Alexandrian. In this paper, I am looking at this rather entertaining story of misunderstood intentions in order to suggest that even though Cavafy himself may be shown to have enjoyed history as fragmented experience, and despite the fact that the modern archive is one of often conflicting partialities rather than one of completeness, we, as consumers of Cavafy’s oeuvre, tend to sustain his long-established position as a paragon of Greek culture, canonised through his own nonconformity. As a typical case of ‘archive fever’, the events described here confirm the political specificity of any literary discourse, even when conducted out of context (or especially so).
Tsipi D, Botitsi H, Economou A. Pesticide chemistry and risk assessment. Mass spectrometry for the analysis of pesticide residues and their metabolitesMass Spectrometry for the Analysis of Pesticide Residues and Their Metabolites. 2015:1-34.
The recent IceCube discovery of 0.1-1 PeV neutrinos of astrophysical origin opens up a new era for high-energy astrophysics. Although there are various astrophysical candidate sources, a firm association of the detected neutrinos with one (or more) of them is still lacking. A recent analysis of plausible astrophysical counterparts within the error circles of IceCube events showed that likely counterparts for nine of the IceCube neutrinos include mostly BL Lacs, among which Mrk 421. Motivated by this result and a previous independent analysis on the neutrino emission from Mrk 421, we test the BL Lac-neutrino connection in the context of a specific theoretical model for BL Lac emission. We model the spectral energy distribution (SED) of the BL Lacs selected as counterparts of the IceCube neutrinos using a one-zone leptohadronic model and mostly nearly simultaneous data. The neutrino flux for each BL Lac is self-consistently calculated, using photon and proton distributions specifically derived for every individual source. We find that the SEDs of the sample, although different in shape and flux, are all well fitted by the model using reasonable parameter values. Moreover, the model-predicted neutrino flux and energy for these sources are of the same order of magnitude as those of the IceCube neutrinos. In two cases, namely Mrk 421 and 1H 1914-194, we find a suggestively good agreement between the model prediction and the detected neutrino flux. Our predictions for all the BL Lacs of the sample are in the range to be confirmed or disputed by IceCube in the next few years of data sampling.
The recent IceCube discovery of 0.1-1 PeV neutrinos of astrophysical origin opens up a new era for high-energy astrophysics. Although there are various astrophysical candidate sources, a firm association of the detected neutrinos with one (or more) of them is still lacking. A recent analysis of plausible astrophysical counterparts within the error circles of IceCube events showed that likely counterparts for nine of the IceCube neutrinos include mostly BL Lacs, among which Mrk 421. Motivated by this result and a previous independent analysis on the neutrino emission from Mrk 421, we test the BL Lac-neutrino connection in the context of a specific theoretical model for BL Lac emission. We model the spectral energy distribution (SED) of the BL Lacs selected as counterparts of the IceCube neutrinos using a one-zone leptohadronic model and mostly nearly simultaneous data. The neutrino flux for each BL Lac is self-consistently calculated, using photon and proton distributions specifically derived for every individual source. We find that the SEDs of the sample, although different in shape and flux, are all well fitted by the model using reasonable parameter values. Moreover, the model-predicted neutrino flux and energy for these sources are of the same order of magnitude as those of the IceCube neutrinos. In two cases, namely Mrk 421 and 1H 1914-194, we find a suggestively good agreement between the model prediction and the detected neutrino flux. Our predictions for all the BL Lacs of the sample are in the range to be confirmed or disputed by IceCube in the next few years of data sampling.
The Neolithic settlement of Dispilió (lake Orestiás, northern Greece) is a unique site due to its continual inhabitation from the Middle Neolithic (5400 BC) to the Chalcolithic (3600 BC) and its exceptional location at the shore of Lake Orestiás (also known as Lake Kastoria). The plant landscape shaping of the area has been examined by correlating pollen and non-pollen palynomorphs (NPPs) from both on-site and off-site records. The examined pollen profiles bear concrete evidence of agricultural activities and land use in the area. The local pollen assemblages identified, each of them corresponding either to a different kind or intensity of exploitation of natural resources, display the diachronic evolution of the cultural landscape during more than 2000 years of human activity. The successive phases of intense human impact on vegetation patterns are in good accordance with the periods of major constructing activities described by the archaeological study of the Dispilió settlement. Finally, the differences on palynomorph accumulation pathways of the examined records made possible the distinction between local and “regional” plant landscapes and related human activities.
The polycystins PC1 and PC2 are emerging as major players in mechanotransduction, a process that influences all steps of the invasion/metastasis cascade. We hypothesized that PC1 and PC2 facilitate cancer aggressiveness. Immunoblotting, RT-PCR, semi-quantitative and quantitative real-time PCR and FACS analyses were employed to investigate the effect of polycystin overexpression in colorectal cancer (CRC) cells. The impact of PC1 inhibition on cancer-cell proliferation was evaluated through an MTT assay. In vitro data were analyzed by Student's t-test. HT29 human xenografts were treated with anti-PC1 (extracellular domain) inhibitory antibody and analyzed via immunohistochemistry to determine the in vivo role of PC1 in CRC. Clinical significance was assessed by examining PC1 and PC2 protein expression in CRC patients (immunohistochemistry). In vivo and clinical data were analyzed by non-parametric tests, Kaplan-Meier curves, log-rank test and Cox model. All statistical tests were two-sided. PC1 overexpression promotes epithelial-to-mesenchymal transition (EMT) in HCT116 cells, while PC2 overexpression results in upregulation of the mTOR pathway in SW480 cells. PC1 inhibition causes reduced cell proliferation in CRC cells inducing tumor necrosis and suppressing EMT in HT29 tumor xenografts. In clinical study, PC1 and PC2 overexpression associates with adverse pathological parameters, including invasiveness and mucinous carcinomas. Moreover, PC1 overexpression appears as an independent prognostic factor of reduced recurrence-free survival (HR = 1.016, p = 0.03) and lowers overall survival probability, while aberrant PC2 expression predicts poor overall survival (p = 0.0468). These results support, for the first time, a direct link between mechanosensing polycystins (PC1 and PC2) and CRC progression.
Pomalidomide is a distinct immunomodulatory agent with significant activity in relapsed/refractory multiple myeloma (RRMM). The optimal treatment schedule in patients with RRMM who have received multiple lines of treatment, including bortezomib and lenalidomide, is 4 mg/day on days 1-21 of a 28-day cycle in combination with weekly low-dose dexamethasone. Improved responses and outcomes relative to traditional therapies continue to be confirmed in recently completed and ongoing trials. Pomalidomide exhibits direct tumoricidal, immunomodulatory, anti-angiogenic and anti-inflammatory activities, which facilitate combination therapy with agents with complementary mechanisms of action, resulting in greater anti-myeloma effects than single-agent therapy or previous combination therapies. For example, in combination with proteasome inhibitors and traditional chemotherapeutic agents in doublet or triplet regimens, pomalidomide provides high rates of durable response, and represents an important new treatment option for patients with RRMM requiring effective new therapies. Additionally, pomalidomide maintains its efficacy and tolerability profile in difficult-to-treat patients, including the elderly, patients with poor cytogenetics and those with renal impairment. This review summarises the clinical development of pomalidomide and discusses this effective agent for the treatment of patients with RRMM in the context of current myeloma treatment options, as well as potential future directions to further improve patient outcomes.
The combination of fluticasone propionate (FLP) and salmeterol (SAL) is often used in clinical practice for the treatment of pulmonary disorders. The purpose of this study was to explore the pharmacokinetics (PK) of inhaled FLP and SAL, after concomitant administration, in healthy male and female subjects using two dry powder inhalers. Plasma concentration (C)-time (t) data were obtained from a single dose, two-sequence, two-period, crossover (2 x 2) bioequivalence (BE) study. Activated charcoal was co-administered in order to prohibit absorption from the gastrointestinal tract. A number of 60 subjects were recruited, while 57 of them completed the study and were included in the PK analysis. Initially, PK parameters of FLP and SAL were estimated using the classic non-compartmental methods. Subsequently, BE assessment was applied to the estimated PK parameters of the two dry powder inhalers. Special focus was placed on the population PK analysis of the C-t data, which were pooled together. `Treatment' (i.e., test or reference) and `period' of the BE study were considered as covariates. A variety of structural and residual error models were tested to find the one which best described the plasma C-t data of FLP and SAL. Demographic data were also evaluated for their impact on the PK parameters. Several goodness-of-fit criteria were utilized. The non-compartmental PK estimates of this study were in agreement with previously reported values. The population PK analysis showed that FLP data were described by a two compartment model with first-order absorption and elimination kinetics. Body weight was found to affect significantly absorption rate constant, inter-compartmental clearance, and volume of distribution of the peripheral compartment. As body weight increases, the values of these PK parameters also rise. For SAL, the best results were obtained when a two-compartment disposition model was used assuming very rapid absorption kinetics (like intravenous bolus) and first-order elimination kinetics. Gender was found to be a significant covariate on clearance, with men exhibiting higher clearance than women. (C) 2015 Elsevier B.V. All rights reserved.
Ketamine is an anesthetic with antidepressant properties. The rapid and lasting effect of ketamine observed in preclinical and clinical research makes it a promising therapeutic to improve current major depression (MD) treatment. Our work intended to evaluate whether the combined use of classic antidepressants (imipramine or fluoxetine) and ketamine would improve the antidepressant response. Using an animal model of depressive-like behavior, we show that the addition of ketamine to antidepressants anticipates the behavioral response and accelerates the neuroplastic events when compared with the use of antidepressants alone. In conclusion, our results suggest the need for a reappraisal of the current pharmacological treatment of MD.
Ketamine is an anesthetic with antidepressant properties. The rapid and lasting effect of ketamine observed in preclinical and clinical research makes it a promising therapeutic to improve current major depression (MD) treatment. Our work intended to evaluate whether the combined use of classic antidepressants (imipramine or fluoxetine) and ketamine would improve the antidepressant response. Using an animal model of depressive-like behavior, we show that the addition of ketamine to antidepressants anticipates the behavioral response and accelerates the neuroplastic events when compared with the use of antidepressants alone. In conclusion, our results suggest the need for a reappraisal of the current pharmacological treatment of MD.
Intercostal hernias are rare, and usually occur following injuries of the thoracic wall. The scope of this report is to present a case of a 53-year-old obese patient that developed a transdiaphragmatic intercostal hernia. The patient presented with a palpable, sizeable, reducible mass in the right lateral thoracic wall, with evident bowel sounds in the area, 6 months after a motor-vehicle accident. On computed tomography (CT), the hernia sac contained part of the liver and part of the ascending colon. A surgical repair of the defect was performed, using a prosthetic patch. The patient's postoperative course was uneventful and she remains recurrence free at 12 months after surgery. Intercostal hernias should be suspected following high-impact injuries of the thoracic wall, and CT scans will facilitate the diagnosis of intercostal hernia. We consider the surgical repair of the defect, with placement of a prosthetic mesh, as the treatment of choice to ensure a favorable outcome.
Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.
OBJECTIVES: The objective of this study was to define the natural genotypic variation of the HIV-1 integrase gene across Europe for epidemiological surveillance of integrase strand-transfer inhibitor (InSTI) resistance.
METHODS: This was a multicentre, cross-sectional study within the European SPREAD HIV resistance surveillance programme. A representative set of 300 samples was selected from 1950 naive HIV-positive subjects newly diagnosed in 2006-07. The prevalence of InSTI resistance was evaluated using quality-controlled baseline population sequencing of integrase. Signature raltegravir, elvitegravir and dolutegravir resistance mutations were defined according to the IAS-USA 2014 list. In addition, all integrase substitutions relative to HXB2 were identified, including those with a Stanford HIVdb score ≥ 10 to at least one InSTI. To rule out circulation of minority InSTI-resistant HIV, 65 samples were selected for 454 integrase sequencing.
RESULTS: For the population sequencing analysis, 278 samples were retrieved and successfully analysed. No signature resistance mutations to any of the InSTIs were detected. Eleven (4%) subjects had mutations at resistance-associated positions with an HIVdb score ≥ 10. Of the 56 samples successfully analysed with 454 sequencing, no InSTI signature mutations were detected, whereas integrase substitutions with an HIVdb score ≥ 10 were found in 8 (14.3%) individuals.
CONCLUSIONS: No signature InSTI-resistant variants were circulating in Europe before the introduction of InSTIs. However, polymorphisms contributing to InSTI resistance were not rare. As InSTI use becomes more widespread, continuous surveillance of primary InSTI resistance is warranted. These data will be key to modelling the kinetics of InSTI resistance transmission in Europe in the coming years.
Prions induce lethal neurodegeneration and consist of PrPSc, an aggregated conformer of the cellular prion protein PrPC. Antibody-derived ligands to the globular domain of PrPC (collectively termed GDL) are also neurotoxic. Here we show that GDL and prion infections activate the same pathways. Firstly, both GDL and prion infection of cerebellar organotypic cultured slices (COCS) induced the production of reactive oxygen species (ROS). Accordingly, ROS scavenging, which counteracts GDL toxicity in vitro and in vivo, prolonged the lifespan of prion-infected mice and protected prion-infected COCS from neurodegeneration. Instead, neither glutamate receptor antagonists nor inhibitors of endoplasmic reticulum calcium channels abolished neurotoxicity in either model. Secondly, antibodies against the flexible tail (FT) of PrPC reduced neurotoxicity in both GDL-exposed and prion-infected COCS, suggesting that the FT executes toxicity in both paradigms. Thirdly, the PERK pathway of the unfolded protein response was activated in both models. Finally, 80% of transcriptionally downregulated genes overlapped between prion-infected and GDL-treated COCS. We conclude that GDL mimic the interaction of PrPSc with PrPC, thereby triggering the downstream events characteristic of prion infection.
The performance analysis of the classical M / G / 1 queue, under a general mixed joining/balking strategy was carried out recently by Kerner (Stoch Mod 24:364–375, 2008), who used an analytic approach based on the supplementary variable method. The tractability of the corresponding queueing system with state-dependent arrival rates is particularly significant, as it has important applications in situations where the customers are strategic. In this paper, we present an alternative path for the analysis of the same system, using purely probabilistic arguments.
The novel platinum (II) dimethyl complexes Pt(κ2-L1)Me2 and Pt(κ2-L1)Me2 (1), Pt(κ2-L2a)Me2 (2a) and Pt(κ2-L2b)Me2 (2b) bearing the functionalised N-heterocyclic carbenes (NHCs), L1 = 1-(2-diphenylphosphinoethyl)-3-(2,6-diisopropyl-phenyl)-imidazol-2-ylidene, L2a = 1-(2-pyridyl)-3-(2,6-diisopropyl-phenyl)-imidazol-2-ylidene, L2b = 1-(2-(3-picolinyl))-3-(2, 6-diisopropyl-phenyl)-imidazol-2-ylidene, react with the acid [H(Et2O)2+B(ArF)4-], ArF = 3, 5-(CF3)2C6H3, in the presence of various neutral donors (Dn) to give the salts [{Pt(κ2-L)(Me)(Dn)}+{B(ArF)4}-], where Dn occupies specifically the site trans to the P and the CNHC donor atoms of the coordinated ligands L1 and L2a, L2b, respectively. Spectroscopic data give evidence that the same selectivity prevails when other acids are employed. Activation of the Cl-CH2Cl bond by 2b led to [Pt(κ2-L2b)(Me)Cl], while reaction of CH3I with the dimethyl complexes led to isolable [Pt(κ2-L)Me3I] species.
This paper examines the effects of quantitative easing (QE) announcements by the European Central Bank, the Bank of Japan and the Bank of England on exchange rate dynamics. Using intraday data of three major exchange rates (EUR/USD, GBP/USD, JPY/USD), we apply a univariate APARCH(1,1) model and include QE dummies to empirically investigate how exchange rates are affected in mean and volatility. The empirical results indicate: (i) a direct negative impact on GBP and JPY and no effect of their volatility around the QE announcements of the corresponding central banks, (ii) a delayed devaluation of EUR and an increase of its volatility before and after the ECB’s announcements. Furthermore, the behavior of dynamic conditional correlation among currencies is investigated across the QE announcements. We find a decline in the conditional correlation between EUR and GBP around the announcements by the BoE. These findings highlight the differences on the credibility and effectiveness of the monetary easing strategies and provide important implications from the investors’ and policy makers’ perspective.
We analyzed near-infrared data of the nearby galaxy IC5063 taken with the Very Large Telescope SINFONI instrument. IC5063 is an elliptical galaxy that has a radio jet nearly aligned with the major axis of a gas disk in its center. The data reveal multiple signatures of molecular and atomic gas that has been kinematically distorted by the passage of the jet plasma or cocoon within an area of ∼1 kpc2. Concrete evidence that the interaction of the jet with the gas causes the gas to accelerate comes from the detection of outflows in four different regions along the jet trail: near the two radio lobes, between the radio emission tip and the optical narrow-line-region cone, and at a region with diffuse 17.8 GHz emission midway between the nucleus and the north radio lobe. The outflow in the latter region is biconical, centered 240 pc away from the nucleus, and oriented perpendicularly to the jet trail. The diffuse emission that is observed as a result of the gas entrainment or scattering unfolds around the trail and away from the nucleus with increasing velocity. It overall extends for ≳700 pc parallel and perpendicular to the trail. Near the outflow starting points, the gas has a velocity excess of 600-1200 km s-1 with respect to ordered motions, as seen in [Fe ii], {Pa}α , or {{{H}}}2 lines. High {{{H}}}2 (1-0) S(3)/S(1) flux ratios indicate non-thermal excitation of gas in the diffuse outflow.
We analyzed near-infrared data of the nearby galaxy IC5063 taken with the Very Large Telescope SINFONI instrument. IC5063 is an elliptical galaxy that has a radio jet nearly aligned with the major axis of a gas disk in its center. The data reveal multiple signatures of molecular and atomic gas that has been kinematically distorted by the passage of the jet plasma or cocoon within an area of ∼1 kpc2. Concrete evidence that the interaction of the jet with the gas causes the gas to accelerate comes from the detection of outflows in four different regions along the jet trail: near the two radio lobes, between the radio emission tip and the optical narrow-line-region cone, and at a region with diffuse 17.8 GHz emission midway between the nucleus and the north radio lobe. The outflow in the latter region is biconical, centered 240 pc away from the nucleus, and oriented perpendicularly to the jet trail. The diffuse emission that is observed as a result of the gas entrainment or scattering unfolds around the trail and away from the nucleus with increasing velocity. It overall extends for ≳700 pc parallel and perpendicular to the trail. Near the outflow starting points, the gas has a velocity excess of 600-1200 km s-1 with respect to ordered motions, as seen in [Fe ii], {Pa}α , or {{{H}}}2 lines. High {{{H}}}2 (1-0) S(3)/S(1) flux ratios indicate non-thermal excitation of gas in the diffuse outflow.
BACKGROUND: Liver resection is currently the most efficient curative approach for a wide variety of liver tumors. The application of modern techniques and new surgical devices has improved operative outcomes. Radiofrequency ablation is used more often for liver parenchymal transection. This study aimed to assess the efficacy and safety of radiofrequency ablation-assisted liver resection. METHODS: A retrospective study of 145 consecutive patients who underwent radiofrequency ablation-assisted liver resection was performed. Intraoperative blood loss, need for transfusion or intraoperative Pringle maneuver, the duration of liver parenchymal transection, perioperative complications, and postoperative morbidity and mortality were all evaluated. RESULTS: Fifty minor and ninety-five major liver resections were performed. The mean intraoperative blood loss was 251 mL, with a transfusion rate of 11.7%. The Pringle maneuver was necessary in 12 patients (8.3%). The mean duration for parenchymal transection was 51.75 minutes. There were 47 patients (32.4%) with postoperative complications. There is no mortality within 30 days after surgery. CONCLUSIONS: Radiofrequency ablation-assisted liver resection permits both major and minor liver resections with minimal blood loss and without occlusion of hepatic inflow. Furthermore it decreases the need for blood transfusion and reduces morbidity and mortality. (
N-(4-Chloro-5H-1,2,3-dithiazol-5-ylidene)anilines react with DABCO in hot PhCl to give N-{4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazol-5-ylidene}anilines in high yields (70–92%). The reaction also works with 4-chloro-5H-1,2,3-dithiazol-5-one and -thione, giving the corresponding products in 85% and 76% yields, respectively. While the reaction of several (4-chloro-5H-1,2,3-dithiazol-5-ylidene)methanes with DABCO failed to give {4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazol-5-ylidene}methanes, these can be prepared in moderate yields via classical cycloaddition–retrocycloaddition strategies from 4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazole-5-thione. The 2-chloroethyl moiety on selected dithiazoles was also modified without cleavage of the 1,2,3-dithiazole by reaction with various nucleophiles, giving access to 4-[N-(2-substituted)piperazin-1-yl]-5H-1,2,3-dithiazoles in moderate to high yields.
N-(4-Chloro-5H-1,2,3-dithiazol-5-ylidene)anilines react with DABCO in hot PhCl to give N-{4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazol-5-ylidene}anilines in high yields (70–92%). The reaction also works with 4-chloro-5H-1,2,3-dithiazol-5-one and -thione, giving the corresponding products in 85% and 76% yields, respectively. While the reaction of several (4-chloro-5H-1,2,3-dithiazol-5-ylidene)methanes with DABCO failed to give {4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazol-5-ylidene}methanes, these can be prepared in moderate yields via classical cycloaddition–retrocycloaddition strategies from 4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazole-5-thione. The 2-chloroethyl moiety on selected dithiazoles was also modified without cleavage of the 1,2,3-dithiazole by reaction with various nucleophiles, giving access to 4-[N-(2-substituted)piperazin-1-yl]-5H-1,2,3-dithiazoles in moderate to high yields.
N-(4-Chloro-5H-1,2,3-dithiazol-5-ylidene)anilines react with DABCO in hot PhCl to give N-{4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazol-5-ylidene}anilines in high yields (70–92%). The reaction also works with 4-chloro-5H-1,2,3-dithiazol-5-one and -thione, giving the corresponding products in 85% and 76% yields, respectively. While the reaction of several (4-chloro-5H-1,2,3-dithiazol-5-ylidene)methanes with DABCO failed to give {4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazol-5-ylidene}methanes, these can be prepared in moderate yields via classical cycloaddition–retrocycloaddition strategies from 4-[N-(2-chloroethyl)piperazin-1-yl]-5H-1,2,3-dithiazole-5-thione. The 2-chloroethyl moiety on selected dithiazoles was also modified without cleavage of the 1,2,3-dithiazole by reaction with various nucleophiles, giving access to 4-[N-(2-substituted)piperazin-1-yl]-5H-1,2,3-dithiazoles in moderate to high yields.
Since 2011, Romania has faced an HIV outbreak among injecting drug users (IDUs). Our aim was to identify and describe clinical and epidemiological patterns of this outbreak. A cross-sectional study enrolled 138 IDUs diagnosed with HIV infection between 2011 and 2013 with 58 sexually infected individuals included as the control group. The IDUs had a long history of heroin abuse (10 years) and a recent history of new psychostimulant injection (3-4 years). Classical epidemiological data and molecular techniques were used to describe the transmission dynamics. A high prevalence of hepatitis C virus (HCV) coinfection was noted (98.6%) compared to the control group (10.3%) (p<0.001). IDUs had initially been infected with HCV. HIV infection was more recent, linked to starting injecting stimulants. HIV subtype analysis showed a predominance of the local F1 strain in both IDUs and sexually infected patients; in IDUs it also identified 28 CRF14_BG recombinants and six unique recombinant forms (URFs) between F1 and CRF14_BG. A few patients from both risk groups were infected with subtype B. Among IDUs, CRF14_BG was associated with a lower CD4 cell count and more advanced stages of disease, which correlated with CXCR4 tropism. Phylogenetic analysis revealed the spread of HIV through three major IDU clusters of recent date. Among IDUs with CRF14_BG, some reported travel abroad (Spain, Greece). By identifying clusters of IDUs with related viruses, molecular epidemiologic methods provide valuable information on patterns of HIV transmission that can be useful in planning appropriate harm reduction interventions.
We report the detection of three new X-ray transients and one recurrent X-ray source in recent XMM-Newton observations of the M31 disk. Two 100-ks observations were carried out on 2015-06-28 (ObsID 0763120101; June) and 2015-08-11 (ObsID 0763120301; August).
Goharbari MH, Shadboorestan A, Abdollahi M, Abdolghaffari AH, Baghaei A, Solgi R, Gooshe M, Baeeri M, Abdollahi M, Moridani MY, et al.The reduction of cytochrome c by milk xantine oxidase. International Journal of Pharmacology. 2015;12:30–39.
The cytokine granulocyte colony-stimulating factor (G-CSF) binds to its receptor (G-CSFR) to stimulate hematopoietic stem cell mobilization, myelopoiesis, and the production and activation of neutrophils. In response to exercise-induced muscle damage, G-CSF is increased in circulation and G-CSFR has recently been identified in skeletal muscle cells. While G-CSF/G-CSFR activation mediates pro- and anti-inflammatory responses, our understanding of the role and regulation in the muscle is limited. The aim of this study was to investigate, in vitro and in vivo, the role and regulation of G-CSF and G-CSFR in skeletal muscle under conditions of muscle inflammation and damage. First, C2C12 myotubes were treated with lipopolysaccharide (LPS) with and without G-CSF to determine if G-CSF modulates the inflammatory response. Second, the regulation of G-CSF and its receptor was measured following eccentric exercise-induced muscle damage and the expression levels we investigated for redox sensitivity by administering the antioxidant N-acetylcysteine (NAC). LPS stimulation of C2C12 myotubes resulted in increases in G-CSF, interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNFα) messenger RNA (mRNA) and an increase in G-CSF, IL-6, and MCP-1 release from C2C12 myotubes. The addition of G-CSF following LPS stimulation of C2C12 myotubes increased IL-6 mRNA and cytokine release into the media, however it did not affect MCP-1 or TNFα. Following eccentric exercise-induced muscle damage in humans, G-CSF levels were either marginally increased in circulation or remain unaltered in skeletal muscle. Similarly, G-CSFR levels remained unchanged in response to damaging exercise and G-CSF/G-CSFR did not change in response to NAC. Collectively, these findings suggest that G-CSF may cooperate with IL-6 and potentially promote muscle regeneration in vitro, whereas in vivo aseptic inflammation induced by exercise did not change G-CSF and G-CSFR responses. These observations suggest that different models of inflammation produce a different G-CSF response.
Self-determination theory posits that satisfaction of the needs for autonomy, competence and relatedness represents the basic nutriments for humans’ optimal functioning. It also postulates that with greater the degree to which these three needs are equally satisfied, the quality of motivation is further enhanced. Yet, this premise has remained relatively underexplored. In this correlational study, we surveyed Greek middle-school students (N = 435; 47.1% males; Mage = 13.95; SD = 0.85) and investigated to what extent balanced need satisfaction contributes over and above the need satisfaction in the prediction of quality of motivation in physical education contexts. Path analysis showed that need satisfaction along with balanced need satisfaction were linked with autonomous motivation but not with controlled motivation. The present findings imply that balanced satisfaction of the needs for autonomy, competence and relatedness can be an additional source of optimal motivation and functioning in physical education.
Observations of gamma-ray-bursts and jets from active galactic nuclei reveal that the jet flow is characterized by a high radiative efficiency and that the dissipative mechanism must be a powerful accelerator of non-thermal particles. Shocks and magnetic reconnection have long been considered as possible candidates for powering the jet emission. Recent progress via fully-kinetic particle-in-cell simulations allows us to revisit this issue on firm physical grounds. We show that shock models are unlikely to account for the jet emission. In fact, when shocks are efficient at dissipating energy, they typically do not accelerate particles far beyond the thermal energy, and vice versa. In contrast, we show that magnetic reconnection can deposit more than 50 per cent of the dissipated energy into non-thermal leptons as long as the energy density of the magnetic field in the bulk flow is larger than the rest-mass energy density. The emitting region, i.e. the reconnection downstream, is characterized by a rough energy equipartition between magnetic fields and radiating particles, which naturally accounts for a commonly observed property of blazar jets.
In this article the author argues that the teaching of religion(s) in education, in a social pedagogical context, can encourage community cohesion especially when, during the current harsh crisis, the need for cohesion seems to be of paramount importance in enabling seemingly insurmountable problems to be overcome. At the same time minorities become vulnerable and diversity, a matter of high priority, comes to the fore. The author reviews evidence of research on the effect of educational intervention within Religious Education on student attitudes toward religious diversity. He proposes that constructivist methodology, using theatre/drama as a means of Religious Education, could give people the choice to be critical religious believers and active members in a society applyingthe fundamental social pedagogical principle of tolerance to and respect for the ‘other’.
Religious Education (RE) in Greece is a compulsory school subject according the 2011 new framework for compulsory education, entitled ‘New School’. This article focuses on two statutory documents for RE, ‘The Curriculum for RE’ and the ‘The Teacher’s Guide for RE’, and the pilot scheme of the new curriculum running in school years, 2011–2014, in 188 schools (primary and secondary education). Findings of the research demonstrate that, though the revision seems inevitable, the pedagogical and theological dimension of the RE curriculum is radical as it is based on contemporary theories and methodologies of the construction of the curriculum and RE approaches. However, the article indicates constructivist and critical approaches to RE that influenced the change to an actual non-confessional compulsory subject and also highlighted the tension between an overall constructivist approach to learning and the traditional orthodox content of much of the curriculum. The author opens a discussion on problematic aspects that need to be taken in to consideration when revising the curriculum.
This study is an attempt to address the issue of religion in the public sphere and secularism. Since the Eastern Orthodox Church has been established by the Greek constitution (1975) as the prevailing religion of Greece, there are elements of legal agreements-which inevitably spawn interactions-between state and Church in different areas. One such area is Religious Education. This article focuses on Religious Education (RE) in Greece which is a compulsory school subject and on two important interventions that highlight the interplay between religion, politics and education: firstly the new Curriculum for RE (2011) and secondly the introduction of an Islamic RE (2014) in a Greek region (Thrace) where Christians and Muslims have lived together for more than four centuries. The researches are based on fieldwork research and they attempt to open the discussion on the role of RE in a secular education system and its potential for coexistence and social cohesion.
Karkazis P, Trakadas P, Zahariadis T, Chatzigiannakis I, Dohler M, Vitaletti A, Antoniou A, Leligou HC, Sarakis L. Resource and service virtualisation in M2M and IoT platforms. International Journal of Intelligent Engineering Informatics. 2015;3:205–224.
This work discusses the scientific aspects of the definition of dose as the `highest single oral IR dose' recommended for administration in the SmPC (summary of product characteristics) in the current European Medicines Agency (EMA) 2010 Guideline, for the purpose of biopharmaceutics classification system (BCS)-based biowaiver decision making. Analysis of theoretical and experimental data dealing with drug dissolution and biopharmaceutic drug classification reveals that the drug dose is an important parameter for both drug dissolution and biopharmaceutic classification. The relevant implications for the dose considerations in bioequivalence studies are also discussed briefly. It is suggested that the concept of ``the highest single dose oral IR dose recommended for administration in the SmPC{''} of the EMA 2010 Guideline be abolished. It is advisable, each dose strength be considered separately Le., whether or not it meets the solubility-dissolution regulatory criteria. (C) 2014 Elsevier B.V. All rights reserved.
Damage scenarios were developed for the Lefkada old town (LOT). LOT is the historical center of the capital of Lefkas Island, part of the Ionian Islands, one of the most seismically prone areas within the Mediterranean region that suffered numerous devastating earthquakes in the past. The most recent strong earthquake with Mw = 6.2 occurred on 14 August 2003 at a distance of about 13 km from LOT. A peak ground acceleration (PGA) equal to 0.42 g was recorded in LOT, one of the highest values ever recorded in Greece. Nevertheless, the 2003 event produced limited damage to the buildings of LOT, comprising traditional construction practices of architectural significance and a high seismic behaviour. Towards the development of damage scenarios the following tasks were performed: (a) buildings inventory and vulnerability indices determination using EMS-98 along with behaviour modification scores, (b) subsoil response functions and 1D visco-elastic models calculation using microtremors and (c) stochastic PGA simulation using site amplification deduced from the subsoil response functions. Two scenarios were developed considering the sources of the 2003 M6.2 earthquake and a future M7 event, located at the same fault. The discrete damage probability was resolved by formulating a beta distribution of an average damage grade related to the vulnerability index and the simulated PGA through empirical equations. The deduced models are comparable with the observed 2003 damage distribution, hence they are likely useful for preparing future emergency plans. In the aftermath, although further investigation is needed to explain outliers, the implementation of the followed methodology into an automated procedure for near real time shake and damage maps generation in case of a seismic crisis is highly recommended. The work herein, with proper adaptations, is potentially fairly applicable for other towns and regions in Europe.
This study focuses on a series of small intraplate earthquakes that took place during May–August 2013 on the southwestern coast of the Corinth Rift (Central Greece), a few km southeast of Aigion city. The Corinth Rift is one of the most seismically active parts of the Mediterranean. We analyzed more than 1500 events with 0.4≤ML≤3.7, the major part of which was recorded by a dense local network. The seismicity is densely clustered in a volume of dimensions ∼4×2×6km3, aligned in a N110° direction and at depths ranging between 6 and 12km. Precisely relocated hypocenters and reliably constrained focal mechanisms indicate north dipping planar faults with an average dip of ∼60°. Stress inversion of focal mechanisms implies that the dominant local stress field is extensional in a N5° direction, in good agreement with geodetic observations. The swarm evolved in two phases, with a spatiotemporal migration of epicenters from the eastern toward the western part of the rupture zone, while slip distribution appears homogeneous over the eastern part and strongly inhomogeneous in the western part. These two phases also produced different results in scaling relations such as the Gutenberg–Richter law, the Modified Omori Formula and the Epidemic Type of Aftershock Sequence model. Similar results from other studies have been reported and correlated with a fluid driven mechanism, however further research is required to strengthen this hypothesis for the purposes of this study.
INTRODUCTION: Morphologic homogeneity is desirable in sample selection of clinical studies that evaluate methods of treating craniofacial discrepancies in orthodontics. The purposes of this study were to assess sample selection criteria commonly used in the orthodontic literature regarding their effectiveness in achieving morphologic homogeneity, and to propose a method that can guarantee selection of a homogeneous sample, for which the degree of homogeneity and the average skeletal pattern can be specified a priori.
METHODS: Pretreatment lateral cephalograms from 170 consecutive patients (82 boys, 88 girls) aged 7 to 17 years were used. Sixteen skeletal and 4 dental landmarks were digitized and processed with Procrustes superimposition and principal component analysis. The sample was bootstrapped to a virtual population of 10,000 subjects by random sampling from the normal distribution for each principal component. A systematic literature search of randomized controlled trials showed that the most prevalent sample selection criteria, in addition to molar relationship, included overjet, ANB, and SN-GoGn. Each criterion was applied to the virtual population. The morphologic homogeneity of the samples was assessed as the percentage of shape variance of each sample relative to the shape variance of the population.
RESULTS: The first 3 principal components incorporated approximately 53% of shape variability. The evaluated criteria achieved low or moderate morphologic homogeneity scores (range, 28%-63%), and the selected patients were widely spread in the shape space. Although the criteria are commonly applied for selecting samples with skeletal discrepancies, a considerable number of subjects with an average shape were selected. The proposed procedure entails selecting a skeletal pattern appropriate for the study's purpose, setting limits in shape space within which the sample should be confined, and testing candidate patients against these limits. The patients within these boundaries have, by definition, a similar shape to the selected skeletal pattern and form a homogeneous sample.
CONCLUSIONS: The cephalometric variables that have been used in randomized controlled trials do not result in samples of high morphologic homogeneity. The proposed method guarantees high morphologic homogeneity. The extent of homogeneity, the average shape of the sample, and the sample's relationship to the general population's average can be specified a priori.
Blazars have been suggested as possible neutrino sources long before the recent IceCube discovery of high-energy neutrinos. We re-examine this possibility within a new framework built upon the blazar simplified view and a self-consistent modelling of neutrino emission from individual sources. The former is a recently proposed paradigm that explains the diverse statistical properties of blazars adopting minimal assumptions on blazars' physical and geometrical properties. This view, tested through detailed Monte Carlo simulations, reproduces the main features of radio, X-ray, and γ-ray blazar surveys and also the extragalactic γ-ray background at energies ≳ 10 GeV. Here, we add a hadronic component for neutrino production and estimate the neutrino emission from BL Lacertae objects as a class, `calibrated' by fitting the spectral energy distributions of a preselected sample of such objects and their (putative) neutrino spectra. Unlike all previous papers on this topic, the neutrino background is then derived by summing up at a given energy the fluxes of each BL Lac in the simulation, all characterized by their own redshift, synchrotron peak energy, γ-ray flux, etc. Our main result is that BL Lacs as a class can explain the neutrino background seen by IceCube above ∼0.5 PeV while they only contribute ∼10 per cent at lower energies, leaving room to some other population(s)/physical mechanism. However, one cannot also exclude the possibility that individual BL Lacs still make a contribution at the ≈20 per cent level to the IceCube low-energy events. Our scenario makes specific predictions, which are testable in the next few years.
Both in vitro and in vivo experiments have confirmed that platelet-rich plasma has therapeutic effects on many neuropathies, but its effects on carpal tunnel syndrome remain poorly understood. We aimed to investigate whether single injection of platelet-rich plasma can improve the clinical symptoms of carpal tunnel syndrome. Fourteen patients presenting with median nerve injury who had suffered from mild carpal tunnel syndrome for over 3 months were included in this study. Under ultrasound guidance, 1-2 mL of platelet-rich plasma was injected into the region around the median nerve at the proximal edge of the carpal tunnel. At 1 month after single injection of platelet-rich plasma, Visual Analogue Scale results showed that pain almost disappeared in eight patients and it was obviously alleviated in three patients. Simultaneously, the disabilities of the arm, shoulder and hand questionnaire showed that upper limb function was obviously improved. In addition, no ultrasonographic manifestation of the carpal tunnel syndrome was found in five patients during ultrasonographic measurement of the width of the median nerve. During 3-month follow-up, the pain was not greatly alleviated in three patients. These findings show very encouraging mid-term outcomes regarding use of platelet-rich plasma for the treatment of carpal tunnel syndrome.
Purpose: Clozapine is an atypical neuroleptic agent, effective in treating drug-resistant schizophrenia. The aim of this work was to investigate overall sleep architecture and sleep spindle morphology characteristics, before and after combination treatment with clozapine, in patients with drug-resistant schizophrenia who underwent polysomnography.
Methods: Standard polysomnographic techniques were used. To quantify the sleep spindle morphology, a modeling technique was used that quantifies time-varying patterns in both the spindle envelope and the intraspindle frequency.
Results: After combination treatment with clozapine, the patients showed clinical improvement. In addition, their overall sleep architecture and, more importantly, parameters that quantify the time-varying sleep spindle morphology were affected. Specifically, the results showed increased stage 2 sleep, reduced slow-wave sleep, increased rapid eye movement sleep, increased total sleep time, decreased wake time after sleep onset, as well as effects on spindle amplitude and intraspindle frequency parameters. However, the above changes in overall sleep architecture were statistically nonsignificant trends.
Conclusions: The findings concerning statistically significant effects on spindle amplitude and intraspindle frequency parameters may imply changes in cortical sleep EEG generation mechanisms, as well as changes in thalamic pacing mechanisms or in thalamo-cortical network dynamics involved in sleep EEG generation, as a result of combination treatment with clozapine.
Significance: Sleep spindle parameters may serve as metrics for the eventual development of effective EEG biomarkers to investigate treatment effects and pathophysiological mechanisms in schizophrenia.
An empirical study was conducted to evaluate the users' perception on a pilot mobile application ("SMART Travel Health"), their attitude towards use, and their intention to use it. A theoretical model was constructed based on TAM and other related works. The population was 88 travellers who used the pilot application. Data analysis was performed using partial least squares path modeling. Results highlight the very strong significant effect of perceived ease of use to perceived usefulness, the strong significant effect of perceived usefulness to attitude towards use, as well as, the significant effect of perceived ease of use to attitude towards using the application. Also, the strong significant effect of attitude towards use to behavioral intention to use is presenting the positive perception of the population about this mobile application.
The paper describes a framework for the education of ESOL teachers that is inspired by principles grounded in research on English as a lingua franca (ELF) and world Englishes (WE). The essential feature of such a framework is that it involves interested teachers in a critical reorientation of their beliefs toward English language teaching, learning and communication. This transformative framework informs what we call the ‘ELF-aware’ teacher education component. We then present a framework for a transformative perspective for ELF-aware and WE-aware teachers and describe the phases of a teacher education project that attempted to put this framework into practice.
This work presents the current state of seismic vulnerability in Greece, the most seismically active region in Europe and the corresponding impacts of austerity measures imposed to the nation during the last five years. The analysis of physical risks and socio-economic conditions shows a very dangerous situation, which has to be promptly confronted, in terms of a revised and prioritized National reinforcement effort regarding pre-seismic preparedness and post-seismic interventions. The latter certainly requires funding, however it has to be coupled with restorative measures for the existing socio-political status embracing authorities, communities and individuals.
The inverse Compton catastrophe is defined as a dramatic rise in the luminosity of inverse Compton scattered photons. It is described by a non-linear loop of radiative processes that sets in for high values of the electron compactness and is responsible for the efficient transfer of energy from electrons to photons, predominantly through inverse Compton scatterings. We search for the conditions that drive a magnetized non-thermal source to the inverse Compton catastrophe regime and study its multiwavelength (MW) photon spectrum. We develop a generic analytical framework and use numerical calculations as a backup to the analytical predictions. We find that the escaping radiation from a source in the Compton catastrophe regime bears some unique features. The MW photon spectrum is a broken power law with a break at ∼mec2 due to the onset of the Klein-Nishina suppression. The spectral index below the break energy depends on the electron and magnetic compactnesses logarithmically, while it is independent of the electron power-law index (s). The maximum radiating power emerges typically in the γ-ray regime, at energies ∼mec2 (∼γmax mec2) for s > 2 (s ≲ 2), where γmax is the maximum Lorentz factor of the injected electron distribution. We apply the principles of the inverse Compton catastrophe to blazars and γ-ray bursts using the analytical framework we developed, and show how these can be used to impose robust constraints on the source parameters.
The inverse Compton catastrophe is defined as a dramatic rise in the luminosity of inverse Compton scattered photons. It is described by a non-linear loop of radiative processes that sets in for high values of the electron compactness and is responsible for the efficient transfer of energy from electrons to photons, predominantly through inverse Compton scatterings. We search for the conditions that drive a magnetized non-thermal source to the inverse Compton catastrophe regime and study its multiwavelength (MW) photon spectrum. We develop a generic analytical framework and use numerical calculations as a backup to the analytical predictions. We find that the escaping radiation from a source in the Compton catastrophe regime bears some unique features. The MW photon spectrum is a broken power law with a break at ∼mec2 due to the onset of the Klein-Nishina suppression. The spectral index below the break energy depends on the electron and magnetic compactnesses logarithmically, while it is independent of the electron power-law index (s). The maximum radiating power emerges typically in the γ-ray regime, at energies ∼mec2 (∼γmax mec2) for s > 2 (s ≲ 2), where γmax is the maximum Lorentz factor of the injected electron distribution. We apply the principles of the inverse Compton catastrophe to blazars and γ-ray bursts using the analytical framework we developed, and show how these can be used to impose robust constraints on the source parameters.
An important contribution to the thermoelectric and spin-caloric transport properties in magnetic materials at elevated temperatures is the formation of a spin-disordered state due to local moment fluctuations. This effect has not been largely investigated so far. We focus on various magnetic nanostructures of CrTe in the form of thin layers or nanowires embedded in ZnTe matrix, motivated by the miniaturization of spintronics devices and by recent suggestions that magnetic nanostructures can lead to extraordinary thermoelectric effects due to quantum confinement. The electronic structure of the studied systems is calculated within the multiple scattering screened Korringa-Kohn-Rostoker Green function (KKR-GF) framework. The Monte Carlo method is used to simulate the magnetization in the temperature induced spin disorder. The transport properties are evaluated from the transmission probability obtained using the Baranger-Stone approach within the KKR-GF framework. We find qualitative and quantitative changes in the thermoelectric and spin-caloric coefficients when spin disorder is included in the calculation. Furthermore, we show that substitutional impurities in CrTe nanowires could considerably enhance the Seebeck coefficient and the thermoelectric figure of merit.
We present the statistics of the ratio, R, between the prompt and afterglow “plateau” fluxes of gamma-ray bursts (GRBs). We define this as the ratio of the mean prompt energy flux in Swift BAT and the Swift XRT one, immediately following the steep transition between these two states and the beginning of the afterglow stage referred to as the “plateau”. Like the distribution of many other GRB observables, the histogram of R is log-normal with maximum at a value {{R}m}≃ 2000, FWHM of about two decades, and with the entire distribution spanning about five decades in the value of R. We note that the peak of the distribution is close to the proton-to-electron mass ratio ({{R}m}≃ {{m}p}/{{m}e}=1836), as proposed to be the case in an earlier publication, on the basis of a specific model of the GRB dissipation process. It therefore appears that, in addition to the values of the energy of peak luminosity {{E}pk}∼ {{m}e}{{c}2}, GRBs present us with one more quantity with an apparent characteristic value. The fact that the values of both these quantities ({{E}pk} and R) are consistent with the same specific model invoked to account for the efficient conversion of their relativistic proton energies to electrons argues favorably for its underlying assumptions.
The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries, and the relative impact of two scenarios was considered: (i) increased treatment efficacy while holding the treated population constant and (ii) increased treatment efficacy and increased annual treated population. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. In most countries, the annual treated population had to increase several fold to achieve the largest reductions in HCV-related morbidity and mortality. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. In most of the studied countries, the majority of patients were born between 1945 and 1985.
Stress exposure triggers cognitive and behavioral impairments that influence decision-making processes. Decisions under a context of uncertainty require complex reward-prediction processes that are known to be mediated by the mesocorticolimbic dopamine (DA) system in brain areas sensitive to the deleterious effects of chronic stress, in particular the orbitofrontal cortex (OFC). Using a decision-making task, we show that chronic stress biases risk-based decision-making to safer behaviors. This decision-making pattern is associated with an increased activation of the lateral part of the OFC and with morphological changes in pyramidal neurons specifically recruited by this task. Additionally, stress exposure induces a hypodopaminergic status accompanied by increased mRNA levels of the dopamine receptor type 2 (Drd2) in the OFC; importantly, treatment with a D2/D3 agonist quinpirole reverts the shift to safer behaviors induced by stress on risky decision-making. These results suggest that the brain mechanisms related to risk-based decision-making are altered after chronic stress, but can be modulated by manipulation of dopaminergic transmission.
Stress exposure triggers cognitive and behavioral impairments that influence decision-making processes. Decisions under a context of uncertainty require complex reward-prediction processes that are known to be mediated by the mesocorticolimbic dopamine (DA) system in brain areas sensitive to the deleterious effects of chronic stress, in particular the orbitofrontal cortex (OFC). Using a decision-making task, we show that chronic stress biases risk-based decision-making to safer behaviors. This decision-making pattern is associated with an increased activation of the lateral part of the OFC and with morphological changes in pyramidal neurons specifically recruited by this task. Additionally, stress exposure induces a hypodopaminergic status accompanied by increased mRNA levels of the dopamine receptor type 2 (Drd2) in the OFC; importantly, treatment with a D2/D3 agonist quinpirole reverts the shift to safer behaviors induced by stress on risky decision-making. These results suggest that the brain mechanisms related to risk-based decision-making are altered after chronic stress, but can be modulated by manipulation of dopaminergic transmission.
Composite magnetoplasmonic nanoparticles with a core-shell morphology exhibit intriguing optical properties and offer impressive opportunities for tailoring in a controllable manner the light-matter interaction at subwavelength dimensions. These properties are usually analyzed in the framework of the quasi-static approximation, which, however, is often inadequate; thus, a full electrodynamic treatment is required. In this respect, we developed a rigorous method for an accurate description of electromagnetic scattering by a gyrotropic sphere coated with a nongyrotropic concentric spherical shell, based on the full multipole expansion of the wave field. The method was applied to specific examples of core-shell cobalt-silver spherical nanoparticles, where the occurrence of strong circular dichroism induced by magnetoplasmonic interaction, which largely exceeds that of homogeneous noble metal nanoparticles in an external magnetic field, was found. Our results were also explained by reference to the quasi-static approximation, which, though it reproduces the main features of the absorption spectra, strongly overestimates circular dichroism in the cases we studied.
Abstract – The study described in this paper is a part of a cross-sectional study which focuses on Greek children in preschool and middle school age and to primary school teachers' concepts and classifications regarding animals and the associated values attached in concepts and classifications; i.e. which entities categorize as animals and which are the categorization criteria they use and if they differ with the course of age. The research was conducted with group and individual interviews and proper modifications of Interview about Instances (IaI) technique. Various groups of children and primary school teachers as a representative group of adults were interviewed for the meaning of the concept "animal", and the constant comparative method was employed to analyze data. Key findings in children ideas are the recording of a limited range of entities, which are categorized as animals, the use of sensory criteria mainly for deciding about the categorization, and especially the humanoriented course of perceptions. Findings indicate that the meaning of the concept of "animal" that both, children and teachers possess is restricted and anthropocentric, as it appears a universal denial of human categorization in animal kingdom. Nonetheless, it seems that the anthropocentric ideas of school children and adults differs qualitatively, as school children, besides taking more anthropocentric stands compared to adults, they are not led so much by ideological and ethical motives in their decisions, a fact that seems to be developed in lateral stages of life. Keywords – Preschool Children, Primary School Pupils, Primary School Teachers, Ideas, Conceptions, Animal.
Sulfate is an essential nutrient with pronounced regulatory effects on cellular metabolism and proliferation. Little is known, however, about how sulfate is sensed by cells. Sul1 and Sul2 are sulfate transporters in the yeast Saccharomyces cerevisiae, strongly induced upon sulfur starvation and endocytosed upon addition of sulfate. We reveal Sul1,2-dependent activation of protein kinase A (PKA) targets upon sulfate-induced exit from growth arrest after sulfur starvation. We provide two major arguments in favor of Sul1 and Sul2 acting as transceptors for signaling to PKA. First, the sulfate analogue, D-glucosamine 2-sulfate, acted as a non-transported agonist of signaling by Sul1 and Sul2. Second, mutagenesis to Gln of putative H+-binding residues, Glu427 in Sul1 or Glu443 in Sul2, abolished transport without affecting signaling. Hence, Sul1,2 can function as pure sulfate sensors. Sul1E427Q and Sul2E443Q are also deficient in sulfate-induced endocytosis, which can therefore be uncoupled from signaling. Overall, our data suggest that transceptors can undergo independent conformational changes each responsible for triggering different downstream processes. The Sul1 and Sul2 transceptors are the first identified plasma membrane sensors for extracellular sulfate. High-affinity transporters induced upon starvation for their substrate may generally act as transceptors during exit from starvation.
Magnetoresistance effects observed in ferromagnet/superconductor (FM/SC) hybrids, FM/SC bilayers (BLs) and FM/SC/FM trilayers (TLs), have attracted much interest. Here, we focus on the stray-fields-based superconducting magnetoresistance effect (sMRE) observed in Co(d(Co))/Nb(d(Nb))/Co(d(Co)) TLs with sufficiently thick Co outer layers so that out-of-plane magnetic domains (MDs) and MDs walls (MDWs) emerge all over their surface when subjected to a parallel external magnetic field, H-ex, equal to the coercive field, H-c. To explore the conditions necessary for maximization of the sMRE, we focus on the different kinds of the stray dipolar fields, H-dip, that emerge at the interior of the out-of-plane MDs and at the boundaries of MDWs; these have a different inherent tendency to create straight and semi-loop vortices, respectively. In the recent literature, the creation of straight and semi-loop vortices has been addressed at some extent both theoretically [Laiho et al., Phys. Rev. B 67, 144522 (2003)] and experimentally [Bobba et al., Phys. Rev. B 89, 214502 (2014)] for the case of FM/SC BLs. Here, we address these issues in FM/SC/FM TLs in connection to the sMRE. Specifically, we focus on an experimental finding reported recently [D. Stamopoulos and E. Aristomenopoulou, J. Appl. Phys. 116, 233908 (2014)]; strong magnetostatic coupling of the FM outer layers is accompanied by an intense sMRE in TLs in which the thickness of the SC interlayer, d(SC), matches the width of MDWs, D-MDWs. To investigate this finding, we employ simulations-modeling and energy-considerations and propose two quantitative criteria that facilitate the creation of straight vortices over semi-loop ones. The first focuses on the maximization of the stray H-dip that occur at the interior of the out-of-plane MDs. The second enables the estimation of a crossover between the preferable creation of one kind of vortices over the other. Both criteria respond well, when tested against experimental results. These generic criteria on the interference between d(SC) and D-MDWs can assist the design of cryogenic devices based on FM/SC/FM TLs. (C) 2015 AIP Publishing LLC.
Magnetoresistance is a multifaceted effect reflecting the diverse transport mechanisms exhibited by different kinds of plain materials and hybrid nanostructures; among other, giant, colossal, and extraordinary magnetoresistance versions exist, with the notation indicative of the intensity. Here we report on the superconducting magnetoresistance observed in ferromagnet/superconductor/ ferromagnet trilayers, namely Co/Nb/Co trilayers, subjected to a parallel external magnetic field equal to the coercive field. By manipulating the transverse stray dipolar fields that originate from the out-of-plane magnetic domains of the outer layers that develop at coercivity, we can suppress the supercurrent of the interlayer. We experimentally demonstrate a scaling of the magnetoresistance magnitude that we reproduce with a closed-form phenomenological formula that incorporates relevant macroscopic parameters and microscopic length scales of the superconducting and ferromagnetic structural units. The generic approach introduced here can be used to design novel cryogenic devices that completely switch the supercurrent 'on' and 'off', thus exhibiting the ultimate magnetoresistance magnitude 100% on a regular basis.
We report the detection of three novae in recent XMM-Newton observations of the M31 disk (see also ATel #8227). Two 100-ks observations were carried out on 2015-06-28 (ObsID 0763120101; June) and 2015-08-11 (ObsID 0763120301; August) and have been analysed using the standard data reduction software.
Syndecan-1 is a proteoglycan that acts as co-receptor through its heparan sulfate (HS) chains and plays important roles in cancer. HS chains are highly variable in length and sulfation pattern. This variability is enhanced by the SULF1/2 enzymes, which remove 6-O-sulfates from HS. We used malignant mesothelioma, an aggressive tumor with poor prognosis, as a model and demonstrated that syndecan-1 over-expression down-regulates SULF1 and alters the HS biosynthetic machinery. Biochemical characterization revealed a 2.7-fold reduction in HS content upon syndecan-1 over-expression, but an overall increase in sulfation. Consistent with low SULF1 levels, trisulfated disaccharides increased 2.5-fold. ERK1/2 activity was enhanced 6-fold. Counteracting ERK activation, Akt, WNK1, and c-Jun were inhibited. The net effect of these changes manifested in G1 cell cycle arrest. Studies of pleural effusions showed that SULF1 levels are lower in pleural malignancies compared to benign conditions and inversely correlate with the amounts of syndecan-1, suggesting important roles for syndecan-1 and SULF1 in malignant mesothelioma.
In tectonically active areas, such as in the northwest Peloponnese of western Greece, geomorphic processes are strongly influenced by active faulting; in many cases such faults cannot be easily identified. In this paper we apply multidisciplinary analysis (morphotectonic indices, neotectonic mapping, geophysical surveys and remote sensing techniques) to map the recently-recognized east–west trending Pineios River normal fault zone with a high degree of accuracy, and to better understand its contribution to the evolution of the ancient region of Elis during Holocene time. Fault activity seems to be related to frequent changes in river flow patterns and to displacements of the nearby shoreline. We argue that fault activity is the main reason for migration of Pineios river mouth as documented for several time periods during historical time. Quantitative constraints on deformation caused by the faulting were applied through the application of the morphotectonic indices proposed in this paper, including drainage network asymmetry and sinuosity, and mountain front sinuosity, all of which indicate that this is a highly active structure. Slip rates calculated to be as high as 0.48 mm/yr for the last 209 ka (based on previously published dating) were verified by applied geophysical methods. The fault surface discontinuity was identified at depth using vertical electrical resistivity measurements and depositional layers of different resistivity were found to be clearly offset. Displacement increases toward the west, reaching an observed maximum of 110 m. The most spectacular landform alteration due to surface deformation is the north–south migration of the river estuary into completely different open sea areas during the late Quaternary, mainly during the Holocene. The sediment transport path has been altered several times due to these changes in river geometry with and the most recent seeming to have occurred almost 2000 years ago. The river estuary migrated to its contemporary position along the southern coast, settled on the hanging wall, inducing retrograding of the northern coast, and settled on the foot wall, with rates reaching the order of 0.52 m/yr, as concluded from historical and recently-acquired remote sensing data.
In tectonically active areas, such as in the northwest Peloponnese of western Greece, geomorphic processes are strongly influenced by active faulting; in many cases such faults cannot be easily identified. In this paper we apply multidisciplinary analysis (morphotectonic indices, neotectonic mapping, geophysical surveys and remote sensing techniques) to map the recently-recognized east–west trending Pineios River normal fault zone with a high degree of accuracy, and to better understand its contribution to the evolution of the ancient region of Elis during Holocene time. Fault activity seems to be related to frequent changes in river flow patterns and to displacements of the nearby shoreline. We argue that fault activity is the main reason for migration of Pineios river mouth as documented for several time periods during historical time. Quantitative constraints on deformation caused by the faulting were applied through the application of the morphotectonic indices proposed in this paper, including drainage network asymmetry and sinuosity, and mountain front sinuosity, all of which indicate that this is a highly active structure. Slip rates calculated to be as high as 0.48 mm/yr for the last 209 ka (based on previously published dating) were verified by applied geophysical methods. The fault surface discontinuity was identified at depth using vertical electrical resistivity measurements and depositional layers of different resistivity were found to be clearly offset. Displacement increases toward the west, reaching an observed maximum of 110 m. The most spectacular landform alteration due to surface deformation is the north–south migration of the river estuary into completely different open sea areas during the late Quaternary, mainly during the Holocene. The sediment transport path has been altered several times due to these changes in river geometry with and the most recent seeming to have occurred almost 2000 years ago. The river estuary migrated to its contemporary position along the southern coast, settled on the hanging wall, inducing retrograding of the northern coast, and settled on the foot wall, with rates reaching the order of 0.52 m/yr, as concluded from historical and recently-acquired remote sensing data.
This paper studies subjective priorities for the data amounts in the processing of geopolitical data according to Mazis Ioannis Th., theoretical paradigm of Systemic Geopolitical Analysis. After defining geopolitical plans and geopolitical focus sets, they are introduced geopolitical preferences and geopolitical management capacities. The geopolitical rational choice is studied, as well as the geopolitical preference -capacity distributions. Then, they are investigated geopolitical contrasts of subjective priorities by several geopolitical operators, and it is shown that there are cores and equilibrium of geopolitical contrasts, the study of which may provide useful information.
Biomedical & Health Informatics (BMHI) is relatively new in Arab States. However, several programs/ tracks are running, with high promises of expansion. Programs are evaluated by national authorities, not by a specialized body/association. This does not always mean that the program is of an international standard. One of the possible ways of ensuring the quality of these programs is to be evaluated by international agencies. The International Medical Informatics Association (IMIA) has the expertise in the evaluation BMHI education programs. Accredited programs staffs will have the opportunities for Internationalization and to be engaged with other top-notch organizations, which will have great impacts on the overall implementations of the BMHI in the Arab World. The goal of this document is to show to Arab Universities (pilot: Egypt) how to apply for IMIA Accreditation for their programs.
Combined antiretroviral treatment (cART) modifications are often required due to treatment failure or side effects. We investigate cART regimens' durability, frequency of treatment-limiting adverse events, and potential risk factors and temporal trends. Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). Statistical analyses were based on survival techniques, allowing for multiple contributions per individual. Overall, 2,756 individuals, aged >15 years, initiated cART. cART regimens were grouped by their initiation date into four calendar periods (1995-1998, 1999-2002, 2003-2006, and 2007+). Median [95% confidence interval (CI)] time to first treatment modification was 2.11 (1.95-2.33) years; cumulative probabilities at 1 year were 31.6%, 29.0%, 33.1%, and 29.6% for the four periods, respectively. cART modifications were less frequent in more recent years (adjusted HR=0.96 per year; p<0.001). Longer treatment duration was associated with lower HIV-RNA, higher CD4 counts, and being previously ART naive. cART modifications due to treatment failure became less frequent in recent years (adjusted HR=0.91 per year; p<0.001). Estimated (95% CI) 1 year cumulative probabilities of treatment-limiting side effects were 16.4% (12.0-21.3%), 19.3% (15.6-23.3%), 24.9% (20.3-29.7%), and 21.1% (13.4-29.9%) for the four periods, respectively, with no significant temporal trends. Risk of side effects was lower in nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens or triple nucleoside reverse transcriptase inhibitor (NRTI)-based cART regimens. Treatment modifications have become less frequent in more recent years. This could be partly attributed to the lower risk for side effects of NNRTI-based cART regimens and mainly to the improved efficacy of newer drugs. However, the rate of drugs substitutions due to adverse events remains substantially high.
We call monomer a B-DNA base pair and examine, analytically and numerically, electron or hole oscillations in monomer and dimer polymers, i.e., periodic sequences with repetition unit made of one or two monomers. We employ a tight-binding (TB) approach at the base-pair level to readily determine the spatiotemporal evolution of a single extra carrier along a N base-pair B-DNA segment. We study highest occupied molecular orbital and lowest unoccupied molecular orbital eigenspectra as well as the mean over time probabilities to find the carrier at a particular monomer. We use the pure mean transfer rate k to evaluate the easiness of charge transfer. The inverse decay length β for exponential fits k(d), where d is the charge transfer distance, and the exponent η for power-law fits k(N) are computed; generally power-law fits are better. We illustrate that increasing the number of different parameters involved in the TB description, the fall of k(d) or k(N) becomes steeper and show the range covered by β and η. Finally, for both the time-independent and the time-dependent problems, we analyze the palindromicity and the degree of eigenspectrum dependence of the probabilities to find the carrier at a particular monomer.
Accurate prognosis is a key factor in establishing optimal therapeutic decisions; yet in the case of bladder cancer (BlCa) current prognostic indicators cannot ensure optimal disease management. Here, we aimed to evaluate the previously unexplored clinical potential of the urological cancer-related miR-145, miR-143 and miR-224 in BlCa. A total of 279 bladder tissue specimens were included in this study (133 BlCa, 107 adjacent normal and 39 healthy samples). Total RNA was extracted from tissues, it was polyadenylated and reverse transcribed to cDNA. The expression of target molecules was measured via quantitative real-time PCR. The expression levels of both miR-143 and miR-145 were significantly decreased, whereas those of miR-224 were increased in BlCa. Receiver operating characteristic curve analysis indicated a significant discriminatory capacity for miR-143/miR-145 levels. Important associations with disease aggressiveness were observed for all three microRNAs; elevated levels were observed in tumors of higher stage and grade, as well as in 'high-risk' TaT1 patients. More importantly, high miR-143/145 levels could effectively prognose inferior overall survival for muscle-invasive patients and could independently predict the progression of superficial tumors. Finally, the combination of miR-143/145 overexpression with the widely used prognostic markers of European Organization for Research and Treatment of Cancer-risk groups or recurrence at the first follow-up cystoscopy resulted to a superior positive prediction of non-muscle-invasive bladder cancer short-term progression compared with the use of the abovementioned markers alone. The cancer-related miR-143, miR-145 and miR-224 were investigated for the first time in the clinical setting of BlCa, and miR-143/145 cluster constitutes a novel marker helpful for providing an enhanced prediction of oncologic outcome for BlCa patients.
Capillary electrophoresis is a separation technique with high resolving power and sensitivity with applications in glycosaminoglycan analysis. In this chapter, we present validated protocols for determining the variously sulfated chondroitin or dermatan sulfate-derived disaccharides. These approaches involve degradation of the polysaccharides with specific chondro/dermato-lyases and electrophoretic analysis with capillary zone electrophoresis in a low pH operating buffer and reversed polarity. This methodology has been applied to drug/nutraceutical formulations or to biologic samples (blood serum, lens capsule) and has been validated. Analysis of biologic tissue samples is often more demanding in terms of detection sensitivity, and thus concentration pretreatment steps and/or a derivatization step with 2-aminoacridone are often advisable.
In this article we provide evidence that the verbalizing v head in Greek has a morphological exponence in many more verbs than is apparent. Although, at first sight, verbs in the traditional second conjugation inflectional class (which exhibit non-root stress, e.g., aɣap-ó ‘I love’, poθ-ó ‘I desire’) do not seem to contain an overt piece of verbalizing morphology, we show that they take a vocalic extension consisting of an abstract vocalic slot. This slot, which can either be filled in with vocalic material or remain empty, undertakes the function of a verbalizer. Two major gains of this analysis is that it provides solid evidence for a v head as a verbalizer and not as a composite Voice-verbalizing head and that it proposes a unified treatment of the Greek verb morphology without extensively retreating to stem allomorphy.
This paper deals with the acoustic analysis of timbral andrhythmic patterns of the Cicada Orni sound activity, collectedat the Plato Academy archaeological site during thesummer period of 2014, comprising the Tettix soundscapedatabase.The main purpose here is to use sound analysis for understandingthe basic patterns of cicada calls and shrillingsounds, and subsequently use the raw material providedby the Tettix database in a statistical modeling frameworkfor creating virtual sounds of cicadas, allowing the controlof synthesis parameters spanning micro, meso and macrotemporal levels.
In view of the relentless increase in antibiotic resistance in human pathogens, efforts are needed to safeguard our future therapeutic options against infectious diseases. In addition to regulatory changes in our antibiotic use, this will have to include the development of new therapeutic compounds. One area that has received growing attention in recent years is the possibility to treat or prevent infections by targeting the virulence mechanisms that render bacteria pathogenic. Antivirulence targets include bacterial adherence, secretion of toxic effector molecules, bacterial persistence through biofilm formation, quorum sensing and immune evasion. Effective small-molecule compounds have already been identified that suppress such processes. In this review, we discuss the susceptibility of such compounds to the development of resistance, by comparison with known resistance mechanisms observed for classical bacteriostatic or bacteriolytic antibiotics, and by review of available experimental case studies. Unfortunately, appearance of resistance mechanisms has already been demonstrated for some, showing that the quest of new, lasting drugs remains complicated.
Quantitative analyses of calcareous nannofossils in the sediments of Pissouri South section on the island of Cyprus have produced a paleoceanographic record reflecting the paleoclimatic conditions during the Zanclean/Piacenzian transition. Pissouri South cyclical lithological alternations between organic-rich laminated layers and grey marls reflect the Earth’s orbital precession. According to the calcareous nannofossil biostratigraphy which has been performed, the studied section is correlated with MNN14/15 and MNN16 calcareous nannofossil biozones and is astronomically dated between 4.065 and 3.217 Ma. Intervals of increased organic carbon content, along with the positive values ofFlorisphaera profunda, Helicosphaera sellii, Discoaster spp. and the subsequent increase of stratification S-index, correspond to the sapropel deposition during periods of wetter climate and intense continental runoff, especially from the river Nile. These layers alternate with grey marly intervals, featured by the increased values of small placoliths of Reticulofenestra and Gephyrocapsaspecies, which are indicative of eutrophic conditions during intense surface-water mixing. Our data support the prevalence of a generally warm phase characterized by the absence of high-frequency climate variations in the southeastern Mediterranean during the Zanclean/Piacenzian (Early/Late Pliocene) transition.
Quantitative analyses of calcareous nannofossils in the sediments of Pissouri South section on the island of Cyprus have produced a paleoceanographic record reflecting the paleoclimatic conditions during the Zanclean/Piacenzian transition. Pissouri South cyclical lithological alternations between organic-rich laminated layers and grey marls reflect the Earth’s orbital precession. According to the calcareous nannofossil biostratigraphy which has been performed, the studied section is correlated with MNN14/15 and MNN16 calcareous nannofossil biozones and is astronomically dated between 4.065 and 3.217 Ma. Intervals of increased organic carbon content, along with the positive values ofFlorisphaera profunda, Helicosphaera sellii, Discoaster spp. and the subsequent increase of stratification S-index, correspond to the sapropel deposition during periods of wetter climate and intense continental runoff, especially from the river Nile. These layers alternate with grey marly intervals, featured by the increased values of small placoliths of Reticulofenestra and Gephyrocapsaspecies, which are indicative of eutrophic conditions during intense surface-water mixing. Our data support the prevalence of a generally warm phase characterized by the absence of high-frequency climate variations in the southeastern Mediterranean during the Zanclean/Piacenzian (Early/Late Pliocene) transition.
Η εργασία αυτή προβαίνει σε μια ανασκόπηση των θεωρητικών προσεγγίσεων περί κοινωνικού κεφαλαίου, γεφυροποιού και αποκλειστικού, με σκοπό την προσέγγιση της κοινωνικής περιοχής του αθλητισμού και του φύλου υπό την οπτική της ανάλυσης του κοινωνικού κεφαλαίου και κατ’ επέκταση τη συμβολή της αθλήτριας στην παραγωγή του κοινωνικού κεφαλαίου. Η διεθνής βιβλιογραφία στο θέμα «ο αθλητισμός ως κοινωνικό κεφάλαιο» μολονότι περιορισμένη, αποδεικνύει ότι όσο ισχυρότερο είναι το κοινωνικό κεφάλαιο που αποκτάται στο πεδίο του αθλητισμού, τόσο διευκολύνεται και προωθείται η κοινωνική ενσωμάτωση. Στις μέχρι τώρα εργασίες για το κοινωνικό κεφάλαιο έχει παραμεληθεί και η παράμετρος φύλο. Η έρευνα της έμφυλης διάστασης του κοινωνικού κεφαλαίου, μολονότι περιορισμένη, δείχνει ότι οι γυναίκες παίζουν σημαντικό ρόλο στην ανάπτυξη του κοινωνικού κεφαλαίου. Το κοινωνικό κεφάλαιο αναφέρεται στη συλλογική αξία των κοινωνικών δικτύων, στην άρση των κοινωνικών αποκλεισμών, που αφορούν την έμφυλη, εθνική και φυλετική πολυμορφία (diverity), μεταξύ άλλων. Συμπερασματικά, είναι απαραίτητο να συμπεριληφθεί η διάσταση του φύλου και ειδικά ο ρόλος της αθλήτριας στις συζητήσεις για το κοινωνικό κεφάλαιο. Η έμφυλη διάσταση λειτουργεί ως «κοινωνική κόλλα», ως ανεκμετάλλευτη πηγή κοινωνικής ενέργειας που συμβάλλει δυναμικά στην αναγνώριση και την ενεργοποίηση κοινωνικών διεργασιών.
Λέξεις-κλειδιά:γεφυροποιό και αποκλειστικό κοινωνικό κεφάλαιο, «κοινωνική κόλλα», έμφυλη διάσταση, αθλητισμός, φύλο, γυναίκες, κοινωνικά δίκτυα -------------------------------------------------------------------------------------------------------Καμπερίδου, Ειρήνη; Παπαδοπούλου, Σοφία (2014). Κοινωνικό Κεφάλαιο, Φύλο και Αθλητισμός. Γυναίκα & Άθληση. Τόμος ΙΧ , 2013/2014, σελ. 7-14. Έκδοση της Πανελλήνιας Ένωσης για τον Αθλητισμό και τα Σπορ (ΠΕΠΓΑΣ). *** Kamberidou, I. ; Papadopoulou, Sophia (2014). Social Capital, Gender and Sport (published in Greek). Women & Sport, a publication of the Hellenic Union for the Advancement of Women and Girls in Sport (PEPGAS), volume ΙΧ , 2013/2014, σελ. 7-14.---------------------------------------------------------------------------
Social Capital, Gender and Sport: This paper explores the concept of social capital—bridging and exclusive— so as to apply it as an analytical category to sport and gender, and subsequently the female athlete’s contributions in social capital production. International research on sport as social capital, although limited, indicates that sport promotes social inclusion. Research on the gender dimension of social capital, although limited, shows that women have been playing a major role in social capital production. Social capital refers to the collective value of social networks, the elimination of social exclusions, respect for ethnic, racial and gender diversity, among other things. In conclusion, it is essential to incorporate the gender perspective, and especially the role of the female athlete, in the discussions on social capital. The gender dimension provides the ‘social glue’ or untapped energy source that contributes dynamically in acknowledging and activating social processes.
Keywords: bridging and exclusive social capital, "social glue", gender dimension, sport, gender perspective, women, social networks.
Η απόφαση της ΣτΕ (Ολ.) 2287/2015 κρίνει ότι επιβάλλεται η εκπόνηση μελέτης οικονομικών και κοινωνικών επιπτώσεων πριν από την επιβολή περικοπών στις συντάξεις. Απαιτείται να εκτιμηθούν συνολικά οι επιπτώσεις από τα φορολογικά και ασφαλιστικά μέτρα. Η απόφαση συνάδει με όσα έχουν γίνει δεκτά από τον Διεθνή Οργανισμό Εργασίας και το Συμβούλιο της Ευρώπης όσον αφορά στη συμμόρφωση της Ελλάδας στις διεθνείς της υποχρεώσεις. Ωστόσο, η απόφαση εσφαλμένα δέχεται ότι τα μέτρα που έχουν ληφθεί κατά τη διάρκεια της κρίσης δεν είναι διαρθρωτικά. Η άποψη της μειοψηφίας στο σημείο αυτό είναι περισσότερο πειστική. Τέλος, στην παρούσα εξαιρετικά κρίσιμη οικονομική συγκυρία και λαμβάνοντας υπόψη ότι η αναφερόμενη στην απόφαση μελέτη των επιπτώσεων απαιτείται το πρώτον, θα έπρεπε να είχε ταχθεί προθεσμία στο Δημόσιο για να προσκομίσει, έστω και εκ των υστέρων, ως συμπληρωματική απόδειξη τη μελέτη αυτή.
The fundamental beliefs and principles underlying the curriculum of a subject in the school system are very important. Philosophy provides curriculum specialists and stakeholders with a framework for building the curriculum. It helps them answer the question what is knowledge, what is of value for learning, how students learn, what methods to use, what are the outcomes of education and what is the role of the teacher in the earning process etc. Different philosophies, such as Idealism, Realism, Critical Realism, Pragmatism and Existentialism provide different answers. The author in this paper is concerned with the Religious Education curriculum for the three last years of High School (Lyceum in Greece). He argues that the curriculum should be defined as the total learning experiences of the individual. For that, Pragmatism which pervades John Dewey’s work and his definition of experience and education, and in some cases Existentialism, should be the basis on which the Religious Education curriculum ought to be constructed. Along similar lines, he argues that pragmatism should be considered with Βahktin’s ‘dialogical self’, Geertz’s ‘grammar of culture’ and the Orthodox theology of the Person. The study puts forward the view that Religious Education might be a modern, not confessional subject, educating adolescents with a ‘religious language’ of themselves and their societies and aiming towards a critical religiosity’, where otherness is a part of ourselves.
Disc winds originating from the inner parts of accretion discs are considered as the basic component of magnetically collimated outflows. The only available analytical magnetohydrodynamic (MHD) solutions to describe disc-driven jets are those characterized by the symmetry of radial self-similarity. However, radially self-similar MHD jet models, in general, have three geometrical shortcomings: (i) a singularity at the jet axis, (ii) the necessary assumption of axisymmetry and (iii) the non-existence of an intrinsic radial scale, i.e. the jets formally extend to radial infinity. Hence, numerical simulations are necessary to extend the analytical solutions towards the axis, by solving the full three-dimensional equations of MHD and impose a termination radius at finite radial distance. We focus here on studying the effects of relaxing the (ii) assumption of axisymmetry, i.e. of performing full 3D numerical simulations of a disc wind crossing all MHD critical surfaces. We compare the results of these runs with previous axisymmetric 2.5D simulations. The structure of the flow in all simulations shows strong similarities. The 3D runs reach a steady state and stay close to axisymmetry for most of the physical quantities, except for the poloidal magnetic field and the toroidal velocity which slightly deviate from axisymmetry. The latter quantities show signs of instabilities, which, however, are confined to the region inside the fast magnetosonic separatrix surface. The forces present in the flow, both of collimating and accelerating nature, are in good agreement in both the 2.5D and the 3D runs. We conclude that the analytical solution behaves well also after relaxing the basic assumption of axisymmetry.
Disc winds originating from the inner parts of accretion discs are considered as the basic component of magnetically collimated outflows. The only available analytical magnetohydrodynamic (MHD) solutions to describe disc-driven jets are those characterized by the symmetry of radial self-similarity. However, radially self-similar MHD jet models, in general, have three geometrical shortcomings: (i) a singularity at the jet axis, (ii) the necessary assumption of axisymmetry and (iii) the non-existence of an intrinsic radial scale, i.e. the jets formally extend to radial infinity. Hence, numerical simulations are necessary to extend the analytical solutions towards the axis, by solving the full three-dimensional equations of MHD and impose a termination radius at finite radial distance. We focus here on studying the effects of relaxing the (ii) assumption of axisymmetry, i.e. of performing full 3D numerical simulations of a disc wind crossing all MHD critical surfaces. We compare the results of these runs with previous axisymmetric 2.5D simulations. The structure of the flow in all simulations shows strong similarities. The 3D runs reach a steady state and stay close to axisymmetry for most of the physical quantities, except for the poloidal magnetic field and the toroidal velocity which slightly deviate from axisymmetry. The latter quantities show signs of instabilities, which, however, are confined to the region inside the fast magnetosonic separatrix surface. The forces present in the flow, both of collimating and accelerating nature, are in good agreement in both the 2.5D and the 3D runs. We conclude that the analytical solution behaves well also after relaxing the basic assumption of axisymmetry.
This contribution presents the development of medical informatics education in Europe. It does not discuss all developments that took place. Rather it discerns several themes that indicate the progress in the field, starting from the initiation phase to the final quality control phase.
Artificial (CoO-)Co/Nb/Co trilayers (TLs) are studied by means of magnetization, transport, and magnetic force microscopy measurements. By using these TLs as a model system, we provide definite means to distinguish the exchange-fields and stray-fields based magnetoresistance effects observed in relevant Ferromagnetic/Superconducting/Ferromagnetic (FM/SC/FM) structures. Accordingly, we isolate and exclusively focus on the stray-fields version, to report a complete supercurrent switch, Delta R/R-nor approximate to 100%, achieved at operating temperature T > 4.2 K. Detailed series of Co(60 nm)/Nb(d(Nb))/Co(60 nm) TLs are studied, in which all crucial parameters that relate to the outer Co layers and to the Nb interlayer were systematically varied to unveil the factors that motivate and/or promote the observed effect. We propose a compact model that fairly captures the underlying physics of the Co(60 nm)/Nb(d(Nb))/Co(60 nm) TLs studied here and can be generalized to assist understanding of the relevant processes in every kind of FM/SC/FM TLs. The presented results and accompanying model are both provocative for basic research and attractive for the design of cryogenic devices. (C) 2014 AIP Publishing LLC.
Bouchet O, Javaudin J-P, Kortebi A, El Abdellaouy H, Brzozowski M, Katsianis D, Mayer C, Guan H, Lebouc M, Fontaine F, et al.ACEMIND: The smart integrated home network. Proceedings - 2014 International Conference on Intelligent Environments, IE 2014. 2014:1-8.
BACKGROUND: Allergic reactions to food can have serious consequences. This systematic review summarizes evidence about the immediate management of reactions and longer-term approaches to minimize adverse impacts.
METHODS: Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after and interrupted time series studies. Experts were consulted for additional studies. There was no language or geographic restrictions. Two reviewers critically appraised the studies using the appropriate tools. Data were not suitable for meta-analysis due to heterogeneity so were narratively synthesized.
RESULTS: Eighty-four studies were included, but two-thirds were at high risk of potential bias. There was little evidence about acute management for non-life-threatening reactions. H1-antihistamines may be of benefit, but this evidence was in part derived from studies on those with cross-reactive birch pollen allergy. Regarding long-term management, avoiding the allergenic food or substituting an alternative was commonly recommended, but apart from for infants with cow's milk allergy, there was little high-quality research on this management approach. To reduce symptoms in children with cow's milk allergy, there was evidence to recommend alternatives such as extensively hydrolyzed formula. Supplements such as probiotics have not proved helpful, but allergen-specific immunotherapy may be disease modifying and therefore warrants further exploration.
CONCLUSIONS: Food allergy can be debilitating and affects a significant number of people. However, the evidence base about acute and longer-term management is weak and needs to be strengthened as a matter of priority.
Aromatase inhibitors block the conversion of androgens to oestrogens and are used for the treatment of hormone-responsive breast cancer in menopause and recently also in premenopausal women. We investigate whether decreased oestrogen synthesis following aromatase inhibition leads to a depressive-like behavioural response in cycling female rats. Using the forced swim test (FST) we estimate the response of acute (three injections in 24 h) and sustained (7 d) letrozole and fluoxetine administration. Acute aromatase inhibition decreases immobility duration in the FST, indicating its antidepressant potential. Instead, sustained aromatase inhibition did not show such antidepressant potential. Testosterone elevation associates with the decreased depressive behaviour in the FST following acute letrozole treatment, but interestingly progesterone explains the increased swimming behaviour. Present findings may have potential implications for women treated with aromatase inhibitors, especially before menopause, as well as for the role of gonadal hormones in the expression of depressive symptoms and antidepressant response.
Aromatase inhibitors block the conversion of androgens to oestrogens and are used for the treatment of hormone-responsive breast cancer in menopause and recently also in premenopausal women. We investigate whether decreased oestrogen synthesis following aromatase inhibition leads to a depressive-like behavioural response in cycling female rats. Using the forced swim test (FST) we estimate the response of acute (three injections in 24 h) and sustained (7 d) letrozole and fluoxetine administration. Acute aromatase inhibition decreases immobility duration in the FST, indicating its antidepressant potential. Instead, sustained aromatase inhibition did not show such antidepressant potential. Testosterone elevation associates with the decreased depressive behaviour in the FST following acute letrozole treatment, but interestingly progesterone explains the increased swimming behaviour. Present findings may have potential implications for women treated with aromatase inhibitors, especially before menopause, as well as for the role of gonadal hormones in the expression of depressive symptoms and antidepressant response.
Two specimens of the coccolithophore Calyptrolithophora pappilifera associated with single exothecal and endothecal coccoliths of Syracosphaera histrica,collected from the North Aegean Sea (NE Mediterranean), have been verified by Scanning Electron Microscopy. The two specimens strengthen previous reported hints that Syracosphaera histrica and Calyptrolithophora pappilifera represent a life-cycle association, documenting accordingly the relationships between the different phases within the genus Syracosphaera.
BACKGROUND & AIMS: Evidence suggests that consuming light-to-moderate amounts of alcohol reduces the risk of dementia and is associated better cognitive function and less cardiovascular disease, relative to those consuming no or heavy alcohol. There are only minimal data on the association between alcohol and brain magnetic resonance imaging (MRI) markers. This study aimed to examine the association between alcohol and brain structure measured with MRI.
METHODS: In this cross-sectional study, high-resolution structural MRI was collected on 589 multi-ethnic community residents of New York aged ≥65 with available alcohol intake assessments via a food frequency questionnaire. Total brain volume (TBV), white matter hyperintensity volume (WMHV), and presence of infarcts were derived from MRI scans with established methods. We examined the association of alcohol intake with these imaging markers using regression models adjusted for demographic, clinical, and vascular risk factors.
RESULTS: Compared to non-drinking, light-to-moderate total alcohol (b = 0.007, p = 0.04) or wine (b = 0.008, p = 0.05) intake, but not beer or liquor intake, was associated with larger TBV. Further analysis showed a dose-response association between alcohol (p-trend = 0.03) or wine (p-trend = 0.006) and TBV. Overall, alcohol intake was not associated with WMHV or brain infarcts.
CONCLUSIONS: Our study suggests that among older adults in the community, light-to-moderate alcohol intake, in particular wine, is associated with larger TBV. These findings suggest that light to moderate alcohol consumption is potentially beneficial for brain aging, but replication is needed.
Nieto A, Wahn U, Bufe A, Eigenmann P, Halken S, Hedlin G, Høst A, Hourihane J, Just J, Lack G, et al.Allergy and asthma prevention 2014. Pediatr Allergy Immunol. 2014.Abstract
Asthma and allergic diseases have become one of the epidemics of the 21st century in developed countries. Much of the success of other areas of Medicine, such as infectious diseases, lies on preventive measures. Thus, much effort is also being placed lately in the prevention of asthma and allergy. This manuscript reviews the current evidence, divided in four areas of activity. Interventions modifying environmental exposure to allergens have provided inconsistent results, with multifaceted interventions being more effective in the prevention of asthma. Regarding nutrition, the use of hydrolysed formulas in high risk infants reduces the incidence of atopic dermatitis, while there is for now not enough evidence to recommend other dietary modifications, prebiotics, probiotics, or other microbial products. Pharmacologic agents used until now for prevention have not proved useful, while there is hope that antiviral vaccines could be useful in the future. Allergen-specific immunotherapy is effective for the treatment of allergic patients with symptoms; the study of its value for primary and secondary prevention of asthma and allergy is in its very preliminary phases. The lack of success in the prevention of these disorders lies on their complexity, which involves many genetic, epigenetic and environmental interactions. There is a need to identify target populations, involved mechanisms and interactions, and the best interventions. These must be effective, feasible, implementable and affordable. This article is protected by copyright. All rights reserved.
The existence of sexual dimorphism in individual elements of the human skeleton allows sex determination and significantly enhances the identification of fragmentary skeletal material. Traditionally, the pelvis and the skull are used for an accurate sex determination. Sometimes they are not available and alternative methods have to be used. The aim of this work is to study the sexual dimorphism of the proximal portion of the posterior femur by analyzing the biometric data of the Purkait's triangle. The studied sample comprises 203 individuals (112 males and 91 females) from the Modern Human Skeletal Reference Collection (The Athens Collection) of the Department of Animal & Human Physiology (National & Kapodistrian University of Athens). The biometric data were analyzed by Discriminant Analysis and equations were generated for sex determination, which gave an overall correct classification of 78.3%. For the right and the left femur the percentages of correct classification were 77.8% and 75.9% respectively. These accuracy rates were compared to those of an Indian population and were found to be lower (86.5% for males and 86.3% for females). The study of sexual dimorphism (SD) in Greek, Indian, European-American and African-American populations gave interesting results. The AB diameter in the Greek sample shows the lowest degree of SD while the AC diameter shows the highest. In the other three population samples, the BC diameter shows the highest degree of SD. We assume that the femur anatomy of the Greeks is the major cause that the Purkait method does not give high rates of correct classification. It is therefore advisable that practitioners exercise caution when using this method on skeletal material from Greece, especially in forensic contexts.
On 10 April 2007, three moderate earthquakes with Mw=4.9–5.1 occurred in the vicinity of Trichonis Lake (W. Greece). A local network composed of 12 three-component digital seismographs was installed in the epicentral area and recorded more than 1600 events. The double-difference algorithm HYPODD, incorporating both catalog and waveform cross-correlation differential travel-time data, was applied for the successful relocation of 1490 earthquakes. The latter led to the distinction of a main NW-SE trending and NE-dipping zone, as well as of three neighboring faults; a conjugate NW-SE striking and SW-dipping marginal fault mapped along the northeastern flanks of the lake; a E-W trending and south-dipping low-angle normal fault, possibly related to the major Agrinio Fault Zone (AFZ), parallel to the northern bank of the lake; a NE-SW striking and NW-dipping normal fault, likely related to a segment of the active Evinos fault, located south of the lake. Calculation of the Coulomb stress induced by the combination of the 1975 Mw=6.0 event and the three largest events of 10 April 2007 on the inferred structures, reveals that most of the seismicity lies within the “stress-loaded” region, except for the westernmost activity, which probably belongs to the deep part of the AFZ. A total of 178 reliable focal mechanisms were determined by regional and local body-wave modeling (5 largest events) and P-wave first motion polarity data. The types of the obtained focal mechanisms are predominantly normal and strike-slip, however, numerous earthquakes were found to exhibit reverse faulting. Inversion of focal mechanism data showed that the prevailing principal horizontal component σ3 is quite homogeneous throughout the activated area with a roughly NW-SE trend, parallel to the strike of the Hellenides. On the contrary, the compressional field σ1 appears in two patterns: NE-SW trending onshore and NW-SE trending beneath the lake. This apparent rotation of σ1 by 90° reveals a complex system enclosed by the suggested NW-SE trending antithetic faults in depths between 7 and 9km. The calculated stress ratios beneath the lake imply that vertical forces are close to the overburden pressure. The overall inferred stress pattern is rather linked to topographic variations, locally imposing increase or decrease of the vertical forces. The presence of the water in the lake possibly plays an additional important role, penetrating through the bedrock, reducing the friction coefficient, while the pore pressure and, consequently, the effective stress increase. Thus, shearing along mature fractures is enhanced, likely yielding the observed diversity.
Health care and information technology in health care is advancing at tremendous speed. We analysed whether the prognoses by Haux et al. - first presented in 2000 and published in 2002 - have been fulfilled in 2013 and which might be the reasons for match or mismatch. Twenty international experts in biomedical and health informatics met in May 2013 in a workshop to discuss match or mismatch of each of the 71 prognoses. After this meeting a web-based survey among workshop participants took place. Thirty-three prognoses were assessed matching; they reflect e.g. that there is good progress in storing patient data electronically in health care institutions. Twenty-three prognoses were assessed mismatching; they reflect e.g. that telemedicine and home monitoring as well as electronic exchange of patient data between institutions is not established as widespread as expected. Fifteen prognoses were assessed neither matching nor mismatching. ICT tools have considerably influenced health care in the last decade, but in many cases not as far as it was expected by Haux et al. in 2002. In most cases this is not a matter of the availability of technical solutions but of organizational and ethical issues. We need innovative and modern information system architectures which support multiple use of data for patient care as well as for research and reporting and which are able to integrate data from home monitoring into a patient centered health record. Since innovative technology is available the efficient and wide-spread use in health care has to be enabled by systematic information management.
The purpose of this study was the overview of current knowledge regarding the use of survivin and its isoforms in prognosis and treatment of breast cancer. An advanced search of Medline was performed using the following search strategy: "(survivin isoforms) OR (survivin transcript variants) AND (breast cancer) AND (neoplasm OR tumor OR cancer OR carcinoma)". Relevant studies were retrieved and processed thoroughly in order to analyze the related data. Besides wild-type survivin full-length transcript, another six splice variants have been identified. Overexpression of survivin and its isoforms leads to shorter overall and disease-free survival; the transcript variants are correlated with apoptosis and could assist prognosis prediction. It has been proved through numerous studies that inhibiting survivin isoforms might become a promising target of drug therapy of carcinomas. Use of small molecule YM155 could offer new therapy for triple negative breast cancer patients, while, chemotherapy with 5-fluorouracil + epirubicin + cyclophosphamide and Tax-Epi could be guided by survivin splice variants measurements. Survivin transcript variants could become prognostic biomarkers and could provide information about clinical management of patients suffering from breast cancer
