Synchrotron x-ray measurement and finite element analysis of residual strain in TIG welded aluminium alloy 2024

Residual strains have been measured in a tungsten inert gas (TIG) butt-welded 2024 aluminum alloy plate using synchrotron X-ray diffraction. Novel two-dimensional strain maps spanning the entire plate reveal steep gradients in residual stress and provide detailed validation data for finite element (FE) analysis. Two variants of a FE model have been used to predict the residual strain distributions, incorporating different levels of plate constraint. The model uses decoupled thermal and elastic- plastic mechanical analyses and successfully predicts the longitudinal and transverse residual strain field over the entire weld. For butt weld geometries, the degree of transverse constraint is shown to be a significant boundary condition, compared to simpler bead-on-plate analyses. The importance of transverse residual strains for detailed model validation is highlighted, together with the need for care in selecting the location for line scans. The residual stress is largest in the heat-affected zone (HAZ), being equal to the local postweld yield stress, though the strength increases subsequently by natural aging. In addition, a halving of the diffraction line width has been observed local to the weld, and this correlates with the microstructural changes in the region

AZD1775 Induces Toxicity Through Double-Stranded DNA Breaks Independently of Chemotherapeutic Agents in p53-Mutated Colorectal Cancer Cells

AZD1775 is a small molecule WEE1 inhibitor used in combination with DNA-damaging agents to cause premature mitosis and cell death in p53-mutated cancer cells. Here we sought to determine the mechanism of action of AZD1775 in combination with chemotherapeutic agents in light of recent findings that AZD1775 can cause double-stranded DNA (DS-DNA) breaks. AZD1775 significantly improved the cytotoxicity of 5-FU in a p53-mutated colorectal cancer cell line (HT29 cells), decreasing the IC50 from 9.3 μM to 3.5 μM. Flow cytometry showed a significant increase in the mitotic marker pHH3 (3.4% vs. 56.2%) and DS-DNA break marker γH2AX (5.1% vs. 50.7%) for combination therapy compared to 5-FU alone. Combination therapy also increased the amount of caspase-3 dependent apoptosis compared to 5-FU alone (4% vs. 13%). The addition of exogenous nucleosides to combination therapy significantly rescued the increased DS-DNA breaks and caspase-3 dependent apoptosis almost to the levels of 5-FU monotherapy. In conclusion, AZD1775 enhances 5-FU cytotoxicity through increased DS-DNA breaks, not premature mitosis, in p53-mutated colorectal cancer cells. This finding is important for designers of future clinical trials when considering the optimal timing and duration of AZD1775 treatment

Moist convection and its upscale effects in simulations of the Indian monsoon with explicit and parametrised convection

In common with many global models, the Met Office Unified Model (MetUM) climate simulations show large errors in Indian summer monsoon rainfall, with a wet bias over the equatorial Indian Ocean, a dry bias over India, and with too weak low-level flow into India. The representation of moist convection is a dominant source of error in global models, where convection must be parametrised, with the errors growing quickly enough to affect both weather and climate simulations. Here we use the first multi- week continental-scale MetUM simulations over India, with grid-spacings that allow explicit convection, to examine how convective parametrisation contributes to model biases in the region. Some biases are improved in the convection-permitting simulations with more intense rainfall over India, a later peak in the diurnal cycle of convective rainfall over land, and a reduced positive rainfall bias over the Indian Ocean. The simulations suggest that the reduced rainfall over the Indian Ocean leads to an enhanced monsoon circulation and transport of moisture into India. Increases in latent heating associated with increased convection over land deepen the monsoon trough and enhance water vapour transport into the continent. In addition, delayed continental convection allows greater surface insolation and, along with the same rain falling in more intense bursts, generates a drier land surface. This increases land-sea temperature contrasts, and further enhances onshore flow. Changes in the low-level water vapour advection into India are dominated by these changes to the flow, rather than to the moisture content in the flow. The results demonstrate the need to improve the representations of convection over both land and oceans to improve simulations of the monsoon

Hazard Analysis of Critical Control Points Assessment as a Tool to Respond to Emerging Infectious Disease Outbreaks

Highly pathogenic avian influenza virus (HPAI) strain H5N1 has had direct and indirect economic impacts arising from direct mortality and control programmes in over 50 countries reporting poultry outbreaks. HPAI H5N1 is now reported as the most widespread and expensive zoonotic disease recorded and continues to pose a global health threat. The aim of this research was to assess the potential of utilising Hazard Analysis of Critical Control Points (HACCP) assessments in providing a framework for a rapid response to emerging infectious disease outbreaks. This novel approach applies a scientific process, widely used in food production systems, to assess risks related to a specific emerging health threat within a known zoonotic disease hotspot. We conducted a HACCP assessment for HPAI viruses within Vietnam’s domestic poultry trade and relate our findings to the existing literature. Our HACCP assessment identified poultry flock isolation, transportation, slaughter, preparation and consumption as critical control points for Vietnam’s domestic poultry trade. Introduction of the preventative measures highlighted through this HACCP evaluation would reduce the risks posed by HPAI viruses and pressure on the national economy. We conclude that this HACCP assessment provides compelling evidence for the future potential that HACCP analyses could play in initiating a rapid response to emerging infectious diseases

Multi-parallel qPCR provides increased sensitivity and diagnostic breadth for gastrointestinal parasites of humans: field-based inferences on the impact of mass deworming

BACKGROUND: Although chronic morbidity in humans from soil transmitted helminth (STH) infections can be reduced by anthelmintic treatment, inconsistent diagnostic tools make it difficult to reliably measure the impact of deworming programs and often miss light helminth infections. METHODS: Cryopreserved stool samples from 796 people (aged 2-81 years) in four villages in Bungoma County, western Kenya, were assessed using multi-parallel qPCR for 8 parasites and compared to point-of-contact assessments of the same stools by the 2-stool 2-slide Kato-Katz (KK) method. All subjects were treated with albendazole and all Ascaris lumbricoides expelled post-treatment were collected. Three months later, samples from 633 of these people were re-assessed by both qPCR and KK, re-treated with albendazole and the expelled worms collected. RESULTS: Baseline prevalence by qPCR (n = 796) was 17 % for A. lumbricoides, 18 % for Necator americanus, 41 % for Giardia lamblia and 15% for Entamoeba histolytica. The prevalence was <1% for Trichuris trichiura, Ancylostoma duodenale, Strongyloides stercoralis and Cryptosporidium parvum. The sensitivity of qPCR was 98% for A. lumbricoides and N. americanus, whereas KK sensitivity was 70% and 32%, respectively. Furthermore, qPCR detected infections with T. trichiura and S. stercoralis that were missed by KK, and infections with G. lamblia and E. histolytica that cannot be detected by KK. Infection intensities measured by qPCR and by KK were correlated for A. lumbricoides (r = 0.83, p < 0.0001) and N. americanus (r = 0.55, p < 0.0001). The number of A. lumbricoides worms expelled was correlated (p < 0.0001) with both the KK (r = 0.63) and qPCR intensity measurements (r = 0.60). CONCLUSIONS: KK may be an inadequate tool for stool-based surveillance in areas where hookworm or Strongyloides are common or where intensity of helminth infection is low after repeated rounds of chemotherapy. Because deworming programs need to distinguish between populations where parasitic infection is controlled and those where further treatment is required, multi-parallel qPCR (or similar high throughput molecular diagnostics) may provide new and important diagnostic information

Stable isotope analysis provides new information on winter habitat use of declining avian migrants that is relevant to their conservation

Winter habitat use and the magnitude of migratory connectivity are important parameters when assessing drivers of the marked declines in avian migrants. Such information is unavailable for most species. We use a stable isotope approach to assess these factors for three declining African-Eurasian migrants whose winter ecology is poorly known: wood warbler Phylloscopus sibilatrix, house martin Delichon urbicum and common swift Apus apus. Spatially segregated breeding wood warbler populations (sampled across a 800 km transect), house martins and common swifts (sampled across a 3,500 km transect) exhibited statistically identical intra-specific carbon and nitrogen isotope ratios in winter grown feathers. Such patterns are compatible with a high degree of migratory connectivity, but could arise if species use isotopically similar resources at different locations. Wood warbler carbon isotope ratios are more depleted than typical for African-Eurasian migrants and are compatible with use of moist lowland forest. The very limited variance in these ratios indicates specialisation on isotopically restricted resources, which may drive the similarity in wood warbler populations' stable isotope ratios and increase susceptibility to environmental change within its wintering grounds. House martins were previously considered to primarily use moist montane forest during the winter, but this seems unlikely given the enriched nature of their carbon isotope ratios. House martins use a narrower isotopic range of resources than the common swift, indicative of increased specialisation or a relatively limited wintering range; both factors could increase house martins' vulnerability to environmental change. The marked variance in isotope ratios within each common swift population contributes to the lack of population specific signatures and indicates that the species is less vulnerable to environmental change in sub-Saharan Africa than our other focal species. Our findings demonstrate how stable isotope research can contribute to understanding avian migrants' winter ecology and conservation status

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

A large-scale study of a poultry trading network in Bangladesh: implications for control and surveillance of avian influenza viruses

Since its first report in 2007, avian influenza (AI) has been endemic in Bangladesh. While live poultry marketing is widespread throughout the country and known to influence AI dissemination and persistence, trading patterns have not been described. The aim of this study is to assess poultry trading practices and features of the poultry trading networks which could promote AI spread, and their potential implications for disease control and surveillance. Data on poultry trading practices was collected from 849 poultry traders during a cross-sectional survey in 138 live bird markets (LBMs) across 17 different districts of Bangladesh. The quantity and origins of traded poultry were assessed for each poultry type in surveyed LBMs. The network of contacts between farms and LBMs resulting from commercial movements of live poultry was constructed to assess its connectivity and to identify the key premises influencing it

The statistical neuroanatomy of frontal networks in the macaque

We were interested in gaining insight into the functional properties of frontal networks based upon their anatomical inputs. We took a neuroinformatics approach, carrying out maximum likelihood hierarchical cluster analysis on 25 frontal cortical areas based upon their anatomical connections, with 68 input areas representing exterosensory, chemosensory, motor, limbic, and other frontal inputs. The analysis revealed a set of statistically robust clusters. We used these clusters to divide the frontal areas into 5 groups, including ventral-lateral, ventral-medial, dorsal-medial, dorsal-lateral, and caudal-orbital groups. Each of these groups was defined by a unique set of inputs. This organization provides insight into the differential roles of each group of areas and suggests a gradient by which orbital and ventral-medial areas may be responsible for decision-making processes based on emotion and primary reinforcers, and lateral frontal areas are more involved in integrating affective and rational information into a common framework

Elimination of Schistosomiasis Transmission in Zanzibar: Baseline Findings before the Onset of a Randomized Intervention Trial.

Gaining and sustaining control of schistosomiasis and, whenever feasible, achieving local elimination are the year 2020 targets set by the World Health Organization. In Zanzibar, various institutions and stakeholders have joined forces to eliminate urogenital schistosomiasis within 5 years. We report baseline findings before the onset of a randomized intervention trial designed to assess the differential impact of community-based praziquantel administration, snail control, and behavior change interventions. In early 2012, a baseline parasitological survey was conducted in ∼20,000 people from 90 communities in Unguja and Pemba. Risk factors for schistosomiasis were assessed by administering a questionnaire to adults. In selected communities, local knowledge about schistosomiasis transmission and prevention was determined in focus group discussions and in-depths interviews. Intermediate host snails were collected and examined for shedding of cercariae. The baseline Schistosoma haematobium prevalence in school children and adults was 4.3% (range: 0-19.7%) and 2.7% (range: 0-26.5%) in Unguja, and 8.9% (range: 0-31.8%) and 5.5% (range: 0-23.4%) in Pemba, respectively. Heavy infections were detected in 15.1% and 35.6% of the positive school children in Unguja and Pemba, respectively. Males were at higher risk than females (odds ratio (OR): 1.45; 95% confidence interval (CI): 1.03-2.03). Decreasing adult age (OR: 1.04; CI: 1.02-1.06), being born in Pemba (OR: 1.48; CI: 1.02-2.13) or Tanzania (OR: 2.36; CI: 1.16-4.78), and use of freshwater (OR: 2.15; CI: 1.53-3.03) showed higher odds of infection. Community knowledge about schistosomiasis was low. Only few infected Bulinus snails were found. The relatively low S. haematobium prevalence in Zanzibar is a promising starting point for elimination. However, there is a need to improve community knowledge about disease transmission and prevention. Control measures tailored to the local context, placing particular attention to hot-spot areas, high-risk groups, and individuals, will be necessary if elimination is to be achieved