Определение предельного состояния при усталости титанового сплава ПТ5В

Полученная характеристика локальной неупругости позволяет контролировать кинетику повреждаемости титанового сплава ПТ5В, косвенно выраженной через ее статистические характеристики распределения на поверхности образца исследуемого материала. Предельное состояние конструкционного материала может быть определено из характеристики упрочнения, как уменьшение интенсивности упрочнения до граничного значения.Отримано характеристику локальної непружності, яка дозволяє контролювати кінетику пошкоджуваності титанового сплаву ПТ5В і непрямо виражена через її статистичні характеристики розподілу на поверхні зразка досліджуваного материалу. Граничний стан конструкційного матеріалу може бути визначено з характеристики зміцнення, як зменшення інтенсивності зміцнення до граничного значення.The obtained characteristic of local inelasticity allows controlling the kinetics of damageability in the PT5V titanium alloy, which is implicitly expressed via its statistical characteristics of distribution along the surface of the specimen made of the material studied. The limiting state of the structural material can be determined from its hardening response as a reduction in the hardening rate to its limiting value

Dealing with uncertainties in environmental burden of disease assessment

Disability Adjusted Life Years (DALYs) combine the number of people affected by disease or mortality in a population and the duration and severity of their condition into one number. The environmental burden of disease is the number of DALYs that can be attributed to environmental factors. Environmental burden of disease estimates enable policy makers to evaluate, compare and prioritize dissimilar environmental health problems or interventions. These estimates often have various uncertainties and assumptions which are not always made explicit. Besides statistical uncertainty in input data and parameters – which is commonly addressed – a variety of other types of uncertainties may substantially influence the results of the assessment. We have reviewed how different types of uncertainties affect environmental burden of disease assessments, and we give suggestions as to how researchers could address these uncertainties. We propose the use of an uncertainty typology to identify and characterize uncertainties. Finally, we argue that uncertainties need to be identified, assessed, reported and interpreted in order for assessment results to adequately support decision making

The Impact of the Extent of Lymphadenectomy on Oncologic Outcomes in Patients Undergoing Radical Cystectomy for Bladder Cancer : A Systematic Review

Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewedPostprin

Green Space Visits among Adolescents: Frequency and Predictors in the PIAMA Birth Cohort Study.

Green space may influence health through several pathways, for example, increased physical activity, enhanced social cohesion, reduced stress, and improved air quality. For green space to increase physical activity and social cohesion, spending time in green spaces is likely to be important

Plan for development of case studies - Deliverable Report AD 15.1 WP 15 - Mixtures, HBM and human health risk

This deliverable describes the activities in task 15.3 leading up to the development of cases studies for mixture health effects and outlines the proposed case studies. The proposed case studies are: · Developmental neurotoxicity beyond polybrominated diphenylethers · Heavy metals and nephrotoxicity · Anti-androgenic chemicals and male reproductive health · Chromium (VI), nickel and polycyclic aromatic hydrocarbons and lung cancer · Addressing exposure misclassification in mixture studies The Addendum provides further details about multi-year perspective and timing, as well as detailed budgetary aspects per case study.HBM4EU- Grant agreement 733032 HORIZON2020 Programmeinfo:eu-repo/semantics/publishedVersio

Toxicity Weighting for Human Biomonitoring Mixture Risk Assessment: A Proof of Concept

Chemical mixture risk assessment has, in the past, primarily focused on exposures quantified in the external environment. Assessing health risks using human biomonitoring (HBM) data provides information on the internal concentration, from which a dose can be derived, of chemicals to which human populations are exposed. This study describes a proof of concept for conducting mixture risk assessment with HBM data, using the population-representative German Environmental Survey (GerES) V as a case study. We first attempted to identify groups of correlated biomarkers (also known as 'communities', reflecting co-occurrence patterns of chemicals) using a network analysis approach ( n = 515 individuals) on 51 chemical substances in urine. The underlying question is whether the combined body burden of multiple chemicals is of potential health concern. If so, subsequent questions are which chemicals and which co-occurrence patterns are driving the potential health risks. To address this, a biomonitoring hazard index was developed by summing over hazard quotients, where each biomarker concentration was weighted (divided) by the associated HBM health-based guidance value (HBM-HBGV, HBM value or equivalent). Altogether, for 17 out of the 51 substances, health-based guidance values were available. If the hazard index was higher than 1, then the community was considered of potential health concern and should be evaluated further. Overall, seven communities were identified in the GerES V data. Of the five mixture communities where a hazard index was calculated, the highest hazard community contained N-Acetyl-S-(2-carbamoyl-ethyl)cysteine (AAMA), but this was the only biomarker for which a guidance value was available. Of the other four communities, one included the phthalate metabolites mono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) with high hazard quotients, which led to hazard indices that exceed the value of one in 5.8% of the participants included in the GerES V study. This biological index method can put forward communities of co-occurrence patterns of chemicals on a population level that need further assessment in toxicology or health effects studies. Future mixture risk assessment using HBM data will benefit from additional HBM health-based guidance values based on population studies. Additionally, accounting for different biomonitoring matrices would provide a wider range of exposures. Future hazard index analyses could also take a common mode of action approach, rather than the more agnostic and non-specific approach we have taken in this proof of concept

Identification of Real-Life Mixtures Using Human Biomonitoring Data: A Proof of Concept Study

Human health risk assessment of chemical mixtures is complex due to the almost infinite number of possible combinations of chemicals to which people are exposed to on a daily basis. Human biomonitoring (HBM) approaches can provide inter alia information on the chemicals that are in our body at one point in time. Network analysis applied to such data may provide insight into real-life mixtures by visualizing chemical exposure patterns. The identification of groups of more densely correlated biomarkers, so-called "communities", within these networks highlights which combination of substances should be considered in terms of real-life mixtures to which a population is exposed. We applied network analyses to HBM datasets from Belgium, Czech Republic, Germany, and Spain, with the aim to explore its added value for exposure and risk assessment. The datasets varied in study population, study design, and chemicals analysed. Sensitivity analysis was performed to address the influence of different approaches to standardise for creatinine content of urine. Our approach demonstrates that network analysis applied to HBM data of highly varying origin provides useful information with regards to the existence of groups of biomarkers that are densely correlated. This information is relevant for regulatory risk assessment, as well as for the design of relevant mixture exposure experiments

Green space, air pollution, traffic noise and mental wellbeing throughout adolescence: Findings from the PIAMA study

BACKGROUND: Green space, air pollution and traffic noise exposure may be associated with mental health in adolescents. We assessed the associations of long-term exposure to residential green space, ambient air pollution and traffic noise with mental wellbeing from age 11 to 20 years. METHODS: We included 3059 participants of the Dutch PIAMA birth cohort who completed the five-item Mental Health Inventory (MHI-5) at ages 11, 14, 17 and/or 20 years. We estimated exposure to green space (the average Normalized Difference Vegetation Index (NDVI) and percentages of green space in circular buffers of 300 m, 1000 m and 3000 m), ambient air pollution (particulate matter (PM10 and PM2.5), nitrogen dioxide, PM2.5 absorbance and the oxidative potential of PM2.5) and road traffic and railway noise (Lden) at the adolescents' home addresses at the times of completing the MHI-5. Associations with poor mental wellbeing (MHI-5 score ≤ 60) were assessed by generalized linear mixed models with a logit link, adjusting for covariates. RESULTS: The odds of poor mental wellbeing at age 11 to 20 years decreased with increasing exposure to green space in a 3000 m buffer (adjusted odds ratio (OR) 0.78 [95% CI 0.68-0.88] per IQR increase in the average NDVI; adjusted OR 0.77 [95% CI 0.67-0.88] per IQR increase in the total percentage of green space). These associations persisted after adjustment for air pollution and road traffic noise. Relationships between mental wellbeing and green space in buffers of 300 m and 1000 m were less consistent. Higher air pollution exposure was associated with higher odds of poor mental wellbeing, but these associations were strongly attenuated after adjustment for green space in a buffer of 3000 m, traffic noise and degree of urbanization. Traffic noise was not related to mental wellbeing throughout adolescence. CONCLUSIONS: Residential exposure to green space may be associated with a better mental wellbeing in adolescents

Are physical symptoms among survivors of a disaster presented to the general practitioner? A comparison between self-reports and GP data

<p>Abstract</p> <p>Background</p> <p>Most studies examining medically unexplained symptoms (MUS) have been performed in primary or secondary care and have examined symptoms for which patients sought medical attention. Disasters are often described as precipitating factors for MUS. However, health consequences of disasters are typically measured by means of questionnaires, and it is not known whether these self-reported physical symptoms are presented to the GP. It is also not known if the self-reported symptoms are related to a medical disorder or if they remain medically unexplained. In the present study, three research questions were addressed. Firstly, were self-reported symptoms among survivors presented to the GP? Secondly, were the symptoms presented to the GP associated with a high level of functional impairment and distress? Thirdly, what was the GP's clinical judgment of the presented symptoms, i.e. were the symptoms related to a medical diagnosis or could they be labeled MUS?</p> <p>Methods</p> <p>Survivors of a man-made disaster (N = 887) completed a questionnaire 3 weeks (T1) and 18 months (T2) post-disaster. This longitudinal health survey was combined with an ongoing surveillance program of health problems registered by GPs.</p> <p>Results</p> <p>The majority of self-reported symptoms was not presented to the GP and survivors were most likely to present persistent symptoms to the GP. For example, survivors with stomachache at both T1 and T2 were more likely to report stomachache to their GP (28%) than survivors with stomachache at only T1 (6%) or only T2 (13%). Presentation of individual symptoms to the GP was not consistently associated with functional impairment and distress. 56 – 91% of symptoms were labeled as MUS after clinical examination.</p> <p>Conclusion</p> <p>These results indicate that the majority of self-reported symptoms among survivors of a disaster are not presented to the GP and that the decision to consult with a GP for an individual symptom is not dependent on the level of impairment and distress. Also, self-reported physical symptoms such as headache, back pain and shortness of breath are likely to remain medically unexplained after the clinical judgment of a GP.</p

Staurosporine augments EGF-mediated EMT in PMC42-LA cells through actin depolymerisation, focal contact size reduction and Snail1 induction – A model for cross-modulation

<p>Abstract</p> <p>Background</p> <p>A feature of epithelial to mesenchymal transition (EMT) relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/δEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST) induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC.</p> <p>Methods</p> <p>PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/δEF1) and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin) were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome.</p> <p>Results</p> <p>When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/δEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4). Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/δEF1 showed a reverse correlation with lower expression values being predictive of increased risk.</p> <p>Conclusion</p> <p>ST in combination with EGF directed a greater EMT via actin depolymerisation and focal contact size reduction, resulting in a loosening of cell-ECM attachment along with Snail1-Zeb1/δEF1 induction. This appeared fundamentally different to the EGF-induced EMT, highlighting the multiple pathways which can regulate EMT. Our findings add support for a functional role for Snail1 in invasive breast cancer.</p