The sensitivity of the tropical circulation and Maritime Continent precipitation to climate model resolution

The dependence of the annual mean tropical precipitation on horizontal resolution is investigated in the atmospheric version of the Hadley Centre General Environment Model (HadGEM1). Reducing the grid spacing from about 350 km to 110 km improves the precipitation distribution in most of the tropics. In particular, characteristic dry biases over South and Southeast Asia including the Maritime Continent as well as wet biases over the western tropical oceans are reduced. The annual-mean precipitation bias is reduced by about one third over the Maritime Continent and the neighbouring ocean basins associated with it via the Walker circulation. Sensitivity experiments show that much of the improvement with resolution in the Maritime Continent region is due to the specification of better resolved surface boundary conditions (land fraction, soil and vegetation parameters) at the higher resolution. It is shown that in particular the formulation of the coastal tiling scheme may cause resolution sensitivity of the mean simulated climate. The improvement in the tropical mean precipitation in this region is not primarily associated with the better representation of orography at the higher resolution, nor with changes in the eddy transport of moisture. Sizeable sensitivity to changes in the surface fields may be one of the reasons for the large variation of the mean tropical precipitation distribution seen across climate models

A Conserved PHD Finger Protein and Endogenous RNAi Modulate Insulin Signaling in Caenorhabditis elegans

Insulin signaling has a profound effect on longevity and the oxidative stress resistance of animals. Inhibition of insulin signaling results in the activation of DAF-16/FOXO and SKN-1/Nrf transcription factors and increased animal fitness. By studying the biological functions of the endogenous RNA interference factor RDE-4 and conserved PHD zinc finger protein ZFP-1 (AF10), which regulate overlapping sets of genes in Caenorhabditis elegans, we identified an important role for these factors in the negative modulation of transcription of the insulin/PI3 signaling-dependent kinase PDK-1. Consistently, increased expression of pdk-1 in zfp-1 and rde-4 mutants contributed to their reduced lifespan and sensitivity to oxidative stress and pathogens due to the reduction in the expression of DAF-16 and SKN-1 targets. We found that the function of ZFP-1 in modulating pdk-1 transcription was important for the extended lifespan of the age-1(hx546) reduction-of-function PI3 kinase mutant, since the lifespan of the age-1; zfp-1 double mutant strain was significantly shorter compared to age-1(hx546). We further demonstrate that overexpression of ZFP-1 caused an increased resistance to oxidative stress in a DAF-16–dependent manner. Our findings suggest that epigenetic regulation of key upstream signaling components in signal transduction pathways through chromatin and RNAi may have a large impact on the outcome of signaling and expression of numerous downstream genes.Leukemia & Lymphoma Society of America (3260-07 Special Fellow Award)Arnold and Mabel Beckman Foundation (Young Investigator Award)United States. National Institutes of Health (Director's New Innovator Award (1 DP2 OD006412-01))United States. National Institutes of Health (grant GM66269)modENCODE (grant U01 HG004270)United States. National Institutes of Health (training grant 5T32 GM07088-34

Applications of CRISPR–Cas systems in neuroscience

Genome-editing tools, and in particular those based on CRISPR-Cas (clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein) systems, are accelerating the pace of biological research and enabling targeted genetic interrogation in almost any organism and cell type. These tools have opened the door to the development of new model systems for studying the complexity of the nervous system, including animal models and stem cell-derived in vitro models. Precise and efficient gene editing using CRISPR-Cas systems has the potential to advance both basic and translational neuroscience research.National Institute of Mental Health (U.S.) (Grant 5DP1-MH100706)National Institute of Mental Health (U.S.) (Grant 1R01-MH110049)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant 5R01DK097768-03

Pediatric patient asthma-related emergency department visits and admissions in Washington, DC, from 2001–2004, and associations with air quality, socio-economic status and age group

BACKGROUND: The District of Columbia (DC) Department of Health, under a grant from the US Centers for Disease Control and Prevention, established an Environmental Public Health Tracking Program. As part of this program, the goals of this contextual pilot study are to quantify short-term associations between daily pediatric emergency department (ED) visits and admissions for asthma exacerbations with ozone and particulate concentrations, and broader associations with socio-economic status and age group. METHODS: Data included daily counts of de-identified asthma-related pediatric ED visits for DC residents and daily ozone and particulate concentrations during 2001–2004. Daily temperature, mold, and pollen measurements were also obtained. After a cubic spline was applied to control for long-term seasonal trends in the ED data, a Poisson regression analysis was applied to the time series of daily counts for selected age groups. RESULTS: Associations between pediatric asthma ED visits and outdoor ozone concentrations were significant and strongest for the 5–12 year-old age group, for which a 0.01-ppm increase in ozone concentration indicated a mean 3.2% increase in daily ED visits and a mean 8.3% increase in daily ED admissions. However, the 1–4 yr old age group had the highest rate of asthma-related ED visits. For 1–17 yr olds, the rates of both asthma-related ED visits and admissions increased logarithmically with the percentage of children living below the poverty threshold, slowing when this percentage exceeded 30%. CONCLUSION: Significant associations were found between ozone concentrations and asthma-related ED visits, especially for 5–12 year olds. The result that the most significant ozone associations were not seen in the age group (1–4 yrs) with the highest rate of asthma-related ED visits may be related to the clinical difficulty in accurately diagnosing asthma among this age group. We observed real increases in relative risk of asthma ED visits for children living in higher poverty zip codes versus other zip codes, as well as similar logarithmic relationships for visits and admissions, which implies ED over-utilization may not be a factor. These results could suggest designs for future epidemiological studies that include more information on individual exposures and other risk factors

A Community Study of Factors Related to Poorly Controlled Asthma among Brazilian Urban Children

BACKGROUND: Asthma constitutes a serious public health problem in many regions of the world, including the city of Salvador, State of Bahia-Brazil. The purpose of this study was to analyse the factors associated with poor asthma control. METHODOLOGY/PRINCIPAL FINDINGS: Two definitions were used for asthma: 1) wheezing in the last 12 months; 2) wheezing in the last 12 months plus other asthma symptoms or asthma diagnosis ever. The definition of poorly controlled asthma was: at least one reported hospitalisation due to asthma and/or high frequency of symptoms, in the last year. Children with poorly controlled asthma (N = 187/374) were compared with wheezing children with controlled asthma regarding age, gender, atopy, parental asthma, rhinitis, eczema, exposure to second hand tobacco smoke, presence of moulds, pets and pests in the house, helminth infections and body mass index. Crude and logistic regression adjusted odds ratios were used as measures of association. There was a higher proportion of poorly controlled asthma among children with eczema (OR = 1.55; 95% CI 1.02; 2.37). The strength of the association was greater among children with eczema and rhinitis (42.6%, 53.4% and 57.7%, respectively, in children who had no rhinitis nor eczema, had only one of those, and had both (p = 0.02 for trend test). The presence of mould in the houses was inversely associated with poorly controlled asthma (OR = 0.54; 95% CI 0.34; 0.87). CONCLUSIONS/SIGNIFICANCE: Our results indicate an association between eczema and poor asthma control in this environment, but emphasize the role of various other individual and environmental factors as determinants of poor control

Does traffic exhaust contribute to the development of asthma and allergic sensitization in children: findings from recent cohort studies

The aim of this review was to assess the evidence from recent prospective studies that long-term traffic pollution could contribute to the development of asthma-like symptoms and allergic sensitization in children. We have reviewed cohort studies published since 2002 and found in PubMed in Oct 2008. In all, 13 papers based on data from 9 cohorts have evaluated the relationship between traffic exposure and respiratory health. All surveys reported associations with at least some of the studied respiratory symptoms. The outcome varied, however, according to the age of the child. Nevertheless, the consistency in the results indicates that traffic exhaust contributes to the development of respiratory symptoms in healthy children. Potential effects of traffic exhaust on the development of allergic sensitization were only assessed in the four European birth cohorts. Long-term exposure to outdoor air pollutants had no association with sensitization in ten-year-old schoolchildren in Norway. In contrast, German, Dutch and Swedish preschool children had an increased risk of sensitization related to traffic exhaust despite fairly similar levels of outdoor air pollution as in Norway. Traffic-related effects on sensitization could be restricted to individuals with a specific genetic polymorphism. Assessment of gene-environment interactions on sensitization has so far only been carried out in a subgroup of the Swedish birth cohort. Further genetic association studies are required and may identify individuals vulnerable to adverse effects from traffic-related pollutants. Future studies should also evaluate effects of traffic exhaust on the development and long term outcome of different phenotypes of asthma and wheezing symptoms

Diagnostic value of fine-needle aspiration biopsy for breast mass: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Fine-needle aspiration biopsy (FNAB) of the breast is a minimally invasive yet maximally diagnostic method. However, the clinical use of FNAB has been questioned. The purpose of our study was to establish the overall value of FNAC in the diagnosis of breast lesions.</p> <p>Methods</p> <p>After a review and quality assessment of 46 studies, sensitivity, specificity and other measures of accuracy of FNAB for evaluating breast lesions were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall accuracy. The sensitivity and specificity for the studies data (included unsatisfactory samples) and underestimation rate of unsatisfactory samples were also calculated.</p> <p>Results</p> <p>The summary estimates for FNAB in diagnosis of breast carcinoma were as follows (unsatisfactory samples was temporarily exluded): sensitivity, 0.927 (95% confidence interval [CI], 0.921 to 0.933); specificity, 0.948 (95% CI, 0.943 to 0.952); positive likelihood ratio, 25.72 (95% CI, 17.35 to 28.13); negative likelihood ratio, 0.08 (95% CI, 0.06 to 0.11); diagnostic odds ratio, 429.73 (95% CI, 241.75 to 763.87); The pooled sensitivity and specificity for 11 studies, which reported unsatisfactory samples (unsatisfactory samples was considered to be positive in this classification) were 0.920 (95% CI, 0.906 to 0.933) and 0.768 (95% CI, 0.751 to 0.784) respectively. The pooled proportion of unsatisfactory samples that were subsequently upgraded to various grade cancers was 27.5% (95% CI, 0.221 to 0.296).</p> <p>Conclusions</p> <p>FNAB is an accurate biopsy for evaluating breast malignancy if rigorous criteria are used. With regard to unsatisfactory samples, futher invasive procedures are required in order to minimize the chance of a missed diagnosis of breast cancer.</p

Behavioral genetics and taste

This review focuses on behavioral genetic studies of sweet, umami, bitter and salt taste responses in mammals. Studies involving mouse inbred strain comparisons and genetic analyses, and their impact on elucidation of taste receptors and transduction mechanisms are discussed. Finally, the effect of genetic variation in taste responsiveness on complex traits such as drug intake is considered. Recent advances in development of genomic resources make behavioral genetics a powerful approach for understanding mechanisms of taste

Economic Impacts of Climate Change on Vegetative Agriculture Markets in Israel

We integrate the combined agricultural production effects of forecasted changes in CO2, temperature and precipitation into a multi-regional, country-wide partial equilibrium positive mathematical programming model. By conducting a meta-analysis of 2103 experimental observations from 259 agronomic studies we estimate production functions relating yields to CO2 concentration and temperature for 55 crops. We apply the model to simulate climate change in Israel based on 15 agricultural production regions. Downscaled projections for CO2 concentration, temperature and precipitation were derived from three general circulation models and four representative concentration pathways, showing temperature increase and precipitation decline throughout most of the county during the future periods 2041–2060 and 2061–2080. Given the constrained regional freshwater and non-freshwater quotas, farmers will adapt by partial abandonment of agriculture lands, increasing focus on crops grown in controlled environments at the expense of open-field and rain-fed crops. Both agricultural production and prices decline, leading to reduced agricultural revenues; nevertheless, production costs reduce at a larger extent such that farming profits increase. As total consumer surplus also augments, overall social welfare rises. We find that this outcome is reversed if the positive fertilization effects of increased CO2 concentrations are overlooked