NMR-Based Prostate Cancer Metabolomics

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by Springer in Methods in Molecular Biology on 22 May 2018.Available online: https://doi.org/10.1007/978-1-4939-7845-8_14acceptedVersio

Compensatory density feedback of Oncomelania hupensis populations in two different environmental settings in China

BACKGROUND: The most recent strategy for schistosomiasis control in the People's Republic of China aims to reduce the likelihood of environmental contamination of schistosome eggs. Despite considerable progress, it is believed that achievements would be further consolidated with additional intermediate host snail control measures. We provide an empirical framework for discerning the relative contribution of intrinsic effects (density feedback) from other extrinsic drivers of snail population dynamics. METHODS: We set up experiments in two study locations to collect reproduction data of Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum. We applied a set of four population dynamic models that have been widely used to study phenomenological time-series data to examine the properties of demographic density feedback patterns from abundance data. We also contrasted the obtained results with the component feedback of density on survival rate to determine whether adult survival was the principal driver of the demographic feedback observed. RESULTS: Demographic density feedback models (Ricker- and Gompertz-logistic) accounted for <99% of Akaike's information criterion model weight, with the Gompertz ranking highest in all O. hupensis population groups. We found some evidence for stronger compensatory feedback in the O. hupensis population from Sichuan compared to a Jiangsu population. Survival rates revealed strong component feedback, but the log-linear relationships (i.e. Gompertz) had less support in the demographic feedback analysis. CONCLUSIONS: Our findings indicate that integrated schistosomiasis control measures must continue to reduce parasite abundance further because intermediate host snail populations tend to grow exponentially at low densities, especially O. hupensis populations in mountainous regions. We conclude that density feedback in adult survival is the principal component contribution to the demographic phenomenon observed in the population fitness (r)-abundance relationship

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1–4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0–8·4) while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6–9·2) for males and 6·5% (5·4–7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782–3252] per 100 000 in males vs s1400 [1279–1524] per 100 000 in females), transport injuries (3322 [3082–3583] vs 2336 [2154–2535]), and self-harm and interpersonal violence (3265 [2943–3630] vs 5643 [5057–6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury

Age as a risk factor for acute mountain sickness upon rapid ascent to 3,700 m among young adult Chinese men

Xu-gang Tang,1 Ji-hang Zhang,1 Jun Qin,1 Xu-bin Gao,1 Qian-ning Li,2 Jie Yu,1 Xiao-han Ding,1 Lan Huang1 1Institute of Cardiovascular Diseases, 2Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, People&rsquo;s Republic of China Background: The aim of this study was to explore the relationship between age and acute mountain sickness (AMS) when subjects are exposed suddenly to high altitude.Methods: A total of 856 young adult men were recruited. Before and after acute altitude exposure, the Athens Insomnia Scale score (AISS) was used to evaluate the subjective sleep quality of subjects. AMS was assessed using the Lake Louise scoring system. Heart rate (HR) and arterial oxygen saturation (SaO2) were measured.Results: Results showed that, at 500 m, AISS and insomnia prevalence were higher in older individuals. After acute exposure to altitude, the HR, AISS, and insomnia prevalence increased sharply, and the increase in older individuals was more marked. The opposite trend was observed for SaO2. At 3,700 m, the prevalence of AMS increased with age, as did severe AMS, and AMS symptoms (except gastrointestinal symptoms). Multivariate logistic regression analysis showed that age was a risk factor for AMS (adjusted odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01&ndash;1.13, P&lt;0.05), as well as AISS (adjusted OR 1.39, 95% CI 1.28&ndash;1.51, P&lt;0.001).Conclusion: The present study is the first to demonstrate that older age is an independent risk factor for AMS upon rapid ascent to high altitude among young adult Chinese men, and pre-existing poor subjective sleep quality may be a contributor to increased AMS prevalence in older subjects. Keywords: acute mountain sickness, age, Athens Insomnia Scale, rapid ascent, slee

Sleep quality changes in insomniacs and non-insomniacs after acute altitude exposure and its relationship with acute mountain sickness

Xu-gang Tang,1&nbsp;Ji-hang Zhang,1&nbsp;Xu-bin Gao,1&nbsp;Qian-ning Li,2&nbsp;Jia-bei Li,1&nbsp;Jie Yu1&nbsp;Jun Qin,1&nbsp;Lan Huang11Institute of Cardiovascular Diseases, 2Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, People&rsquo;s Republic of ChinaObjective: We aimed to observe the changes in subjective sleep quality among insomniacs and non-insomniacs after acute ascending to 3,700 m and its possible relationship with acute mountain sickness (AMS).&nbsp;Methods: A total of 600 adult men were recruited. Subjects&rsquo; subjective sleep quality was evaluated by the Athens Insomnia Scale. AMS was assessed using the Lake Louise scoring system. Arterial oxygen saturation was measured. Results: Despite insomnia resolution in only a few subjects, the prevalence of insomnia among insomniacs remained stable at 90% after rapid ascent to 3,700 m. However, among non-insomniacs, the prevalence of insomnia sharply increased to 32.13% in the first day of altitude exposure and progressively reduced to 4.26% by the 60th day of altitude stay. Moreover, the prevalences of insomnia symptoms decreased more markedly from day 1 to day 60 at 3,700 m among non-insomniacs than among insomniacs. At 3,700 m, the prevalence of AMS among insomniacs was 79.01%, 60.49%, and 32.10% on the first, third, and seventh days, respectively, which was significantly higher than that among non-insomniacs. Multivariate regression revealed that elevated Athens Insomnia Scale scores are an independent risk factor for AMS (adjusted odds ratio 1.388, 95% confidence interval: 1.314&ndash;1.464, P&lt;0.001), whereas high arterial oxygen saturation and long duration of altitude exposure are protective factors against AMS. Conclusion: Our results suggest that the effect of high-altitude exposure on subjective sleep quality is more marked, but disappears more quickly, among non-insomniacs than among insomniacs, whereas AMS is especially common among insomniacs. Moreover, poor subjective sleep quality is a risk factor for AMS. Keywords: Athens Insomnia Scale, arterial oxygen saturation, rapid ascent, sleep&nbsp

Modeling the response of magnetorheological fluid dampers under seismic conditions

Magnetorheological (MR) fluid is a smart material fabricated by mixing magnetic-responsive particles with non-magnetic-responsive carrier fluids. MR fluid dampers are able to provide rapid and reversible changes to their damping coefficient. To optimize the efficiency and effectiveness of such devices, a computational model is developed and presented where the flow field is simulated using the computational fluid dynamics approach, coupled with the magnetohydrodynamics model. Three different inlet pressure profiles were designed to replicate real loading conditions are examined, namely a constant pressure, a sinusoidal pressure profile, and a pressure profile mimicking the 1994 Northbridge earthquake. When the MR fluid damper was in its off-state, a linear pressure drop between the inlet and the outlet was observed. When a uniform perpendicular external magnetic field was applied to the annular orifice of the MR damper, a significantly larger pressure drop was observed across the annular orifice for all three inlet pressure profiles. It was shown that the fluid velocity within the magnetized annular orifice decreased proportionally with respect to the strength of the applied magnetic field until saturation was reached. Therefore, it was clearly demonstrated that the present model was capable of accurately capturing the damping characteristics of MR fluid dampers