PhOTO Zebrafish: A Transgenic Resource for In Vivo Lineage Tracing during Development and Regeneration

Background: Elucidating the complex cell dynamics (divisions, movement, morphological changes, etc.) underlying embryonic development and adult tissue regeneration requires an efficient means to track cells with high fidelity in space and time. To satisfy this criterion, we developed a transgenic zebrafish line, called PhOTO, that allows photoconvertible optical tracking of nuclear and membrane dynamics in vivo. Methodology: PhOTO zebrafish ubiquitously express targeted blue fluorescent protein (FP) Cerulean and photoconvertible FP Dendra2 fusions, allowing for instantaneous, precise targeting and tracking of any number of cells using Dendra2 photoconversion while simultaneously monitoring global cell behavior and morphology. Expression persists through adulthood, making the PhOTO zebrafish an excellent tool for studying tissue regeneration: after tail fin amputation and photoconversion of a ~100µm stripe along the cut area, marked differences seen in how cells contribute to the new tissue give detailed insight into the dynamic process of regeneration. Photoconverted cells that contributed to the regenerate were separated into three distinct populations corresponding to the extent of cell division 7 days after amputation, and a subset of cells that divided the least were organized into an evenly spaced, linear orientation along the length of the newly regenerating fin. Conclusions/Significance: PhOTO zebrafish have wide applicability for lineage tracing at the systems-level in the early embryo as well as in the adult, making them ideal candidate tools for future research in development, traumatic injury and regeneration, cancer progression, and stem cell behavior

Can LANA CITS Support Learning in Autistic Children? A case study evaluation

LANA CITS is a Conversational Intelligent Tutoring System that uses the Visual, Auditory, and Kinaesthetic learning style (VAK). It supports learning in autistic pupils, who are studying in mainstream primary schools. Facilitating the learning of these pupils using traditional teaching within mainstream schools is complex and poorly understood. This paper present investigation into how LANA CITS using VAK learning style model can adapt to autistic pupils learning style and improve their learning in mainstream schools. This paper provides a case study evaluation of three children with high-functioning autism examining the effectiveness of learning with LANA CITS. The case study took place in primary school in Saudi Arabia. The results were positive with the students engaged in the tutorial and the teacher noticed some improvement over classroom activities. This results support for the continuing development, evaluation, and use of CITS for pupils with autism in mainstream schools

A prospective cohort study of neighborhood stress and ischemic heart disease in Japan: a multilevel analysis using the JACC study data

<p>Abstract</p> <p>Background</p> <p>A body of research has shown that neighborhood environment may have an effect on a variety of health outcomes, including cardiovascular disease. One explanation for the mechanism of the effect of neighborhood on cardiovascular disease is psychosocial pathways. Direct evidence for an effect of neighborhood on cardiovascular disease with adjustment for perceived stress at the individual level has not been obtained, however. The Japan Collaborative Cohort Study for the Evaluation of Cancer Risk provides a unique dataset which has aggregated area-based cohorts from 45 areas throughout Japan. The purpose of the present study was to examine the contextual effect of area-level stress on ischemic heart disease using data from a large prospective cohort in Japan.</p> <p>Methods</p> <p>A baseline survey of 110,792 residents of 45 areas aged 40-79 years was conducted between 1988 and 1990. Analysis was restricted to subjects from the 33 of 45 areas providing information about self-rated stress (32183 men and 45896 women). Multilevel Poisson regression models were employed in a two-level structure of individuals nested within the 33 areas. Area-level stress was calculated by sex as the number of persons who rated their stress level as high divided by the total number of subjects in that area. Mortality rate ratios (MRRs) per 1 percentage point increase in area-level stress were estimated with adjustment for compositional individual factors.</p> <p>Results</p> <p>During 15 years of follow-up (1,116,895 person-years), 936 deaths due to ischemic heart disease were recorded. Area-level stress varied from 6% to 22%. In the multivariable models, MRRs of area-level stress were 1.06 (95% confidence interval: 1.00-1.12, p = 0.043) in men and 1.07 (95% confidence interval: 1.00-1.14, p = 0.057) in women.</p> <p>Conclusions</p> <p>Area-level stress affects the likelihood of death due to ischemic heart disease of individuals in men. The present findings may suggest that stress should be considered not only within the individual but also within the neighborhood context.</p

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

The long-term health and wellbeing impacts of Healthy New Towns (HNTs): protocol for a baseline and feasibility study of HNT demonstrator sites in England.

Background: Increasing levels of non-communicable diseases (NCDs), mental health problems, high rates of unhealthy behaviours and health inequalities remain major public health challenges worldwide. In the context of increasing urbanisation, there is an urgent need to understand how evidence that living environments shape health, wellbeing and behaviour can be used to design and deliver healthy environments in local urban settings. The Healthy New Town (HNT) programme implemented in England from 2015 consists of ten major housing developments that aim to improve population health through healthy design principles, new models for integrating health and social care and the creation of strong and connected communities. The programme provides a natural experiment in which to investigate the effects on health, wellbeing and inequalities of large-scale interventions targeting the wider social determinants of health. Methods: The research described in this protocol aims to examine the feasibility of a larger study to assess the longer-term health impacts of HNTs, by addressing two research questions: (1) what are the similarities and differences in the HNT programme developments, processes, contexts and expected impacts and outcomes across HNT sites? and (2) how feasible is the use of data from routine sources and existing HNT evaluations and as the baseline for a definitive study to assess impact on health, wellbeing, behavioural and economic outcomes and programme processes? The research will consist of (a) participatory systems mapping with stakeholders to produce a theoretical framework for a longer-term study on the HNT programme, (b) synthesis of existing qualitative data from local HNT evaluations to understand local processes and intervention mechanisms, (c) scoping local and routinely available data to establish a baseline and feasibility for a longer-term study of health and economic outcomes, and (d) building relationships and recruiting HNT sites into the proposed research. Discussion: The proposed research will produce a theoretical framework and assess the feasibility of a definitive study of outcomes of the HNT programme. This research is necessary to understand how longer-term health, wellbeing, behavioural and economic outcomes can be measured, and to inform a definitive study to generate evidence on the effectiveness of the HNT programme

Changes of overweight and obesity in the adult Swiss population according to educational level, from 1992 to 2007

In many high income developed countries, obesity is inversely associated with educational level. In some countries, a widening gap of obesity between educational groups has been reported. The aim of this study was to assess trends in body mass index (BMI) and in prevalence of overweight and obesity and their association with educational level in the adult Swiss population. Four cross-sectional National health interview surveys conducted in 1992/93 (n = 14,521), 1997 (n = 12,474), 2002 (n = 18,908) and 2007 (n = 17,879) using representative samples of the Swiss population (age range 18-102 years). BMI was derived from self-reported data. Overweight was defined as BMI &gt; or = 25 and &lt;30 kg/m(2), and obesity as BMI &gt; or = 30 kg/m(2). Mean (+/- standard deviation) BMI increased from 24.7 +/- 3.6 in 1992/3 to 25.4 +/- 3.6 kg/m2 in 2007 in men and 22.8 +/- 3.8 to 23.7 +/- 4.3 kg/m(2) in women. Between 1992/3 and 2007, the prevalence of overweight + obesity increased from 40.4% to 49.5% in men and from 22.3% to 31.3% in women, while the prevalence of obesity increased from 6.3% to 9.4% in men and from 4.9% to 8.5% in women. The rate of increase in the prevalence of obesity was greater between 1992/3 and 2002 (men: +0.26%/year; women: +0.31%/year) than between 2002 and 2007 (men: +0.10%/year; women: +0.10%/year). A sizable fraction (approximately 25%) of the increasing mean BMI was due to increasing age of the participants over time. The increase was larger in low than high education strata of the population. BMI was strongly associated with low educational level among women and this gradient remained fairly constant over time. A weaker similar gradient by educational level was apparent in men, but it tended to increase over time. In Switzerland, overweight and obesity increased between 1992 and 2007 and was associated with low education status in both men and women. A trend towards a stabilization of mean BMI levels was noted in most age categories since 2002. The increase in the prevalence of obesity was larger in low education strata of the population. These findings suggest that obesity preventive measures should be targeted according to educational level in Switzerland

The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia

Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings: In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding: Bill & Melinda Gates Foundation