Pseudorapidity Dependence of Particle Production and Elliptic Flow in Asymmetric Nuclear Collisions of p+Al, p+Au, d+Au, and ^{3}He+Au at sqrt[s_{NN}]=200 GeV.

Asymmetric nuclear collisions of p+Al, p+Au, d+Au, and ^{3}He+Au at sqrt[s_{NN}]=200  GeV provide an excellent laboratory for understanding particle production, as well as exploring interactions among these particles after their initial creation in the collision. We present measurements of charged hadron production dN_{ch}/dη in all such collision systems over a broad pseudorapidity range and as a function of collision multiplicity. A simple wounded quark model is remarkably successful at describing the full data set. We also measure the elliptic flow v_{2} over a similarly broad pseudorapidity range. These measurements provide key constraints on models of particle emission and their translation into flow

“We wouldn’t of made friends if we didn’t come to Football United”: the impacts of a football program on young people’s peer, prosocial and cross-cultural relationships

Background Sport as a mechanism to build relationships across cultural boundaries and to build positive interactions among young people has often been promoted in the literature. However, robust evaluation of sport-for-development program impacts is limited. This study reports on an impact evaluation of a sport-for-development program in Australia, Football United®. Methods A quasi-experimental mixed methods design was employed using treatment partitioning (different groups compared had different levels of exposure to Football United). A survey was undertaken with 142 young people (average age of 14.7 years with 22.5% of the sample comprising girls) in four Australian schools. These schools included two Football United and two Comparison schools where Football United was not operating. The survey instrument was composed of previously validated measures, including emotional symptoms, peer problems and relationships, prosocial behaviour, other-group orientation, feelings of social inclusion and belonging and resilience. Face to face interviews were undertaken with a purposeful sample (n = 79) of those who completed the survey. The participants in the interviews were selected to provide a diversity of age, gender and cultural backgrounds. Results Young people who participated in Football United showed significantly higher levels of other-group orientation than a Comparison Group (who did not participate in the program). The Football United boys had significantly lower scores on the peer problem scale and significantly higher scores on the prosocial scale than boys in the Comparison Group. Treatment partitioning analyses showed positive, linear associations between other-group orientation and total participation in the Football United program. A lower score on peer problems and higher scores on prosocial behaviour in the survey were associated with regularity of attendance at Football United. These quantitative results are supported by qualitative data analysed from interviews. Conclusions The study provides evidence of the effects of Football United on key domains of peer and prosocial relationships for boys and other-group orientation for young people in the program sites studied. The effects on girls, and the impacts of the program on the broader school environment and at the community level, require further investigation

Like Mother(-in-Law) Like Daughter? Influence of the Older Generation’s Fertility Behaviours on Women’s Desired Family Size in Bihar, India

This paper investigates the associations between preferred family size of women in rural Bihar, India and the fertility behaviours of their mother and mother-in-law. Scheduled interviews of 440 pairs of married women aged 16–34 years and their mothers-in-law were conducted in 2011. Preferred family size is first measured by Coombs scale, allowing us to capture latent desired number of children and then categorized into three categories (low, medium and high). Women’s preferred family size is estimated using ordered logistic regression. We find that the family size preferences are not associated with mother’s fertility but with mother’s education. Mother-in-law’s desired number of grandchildren is positively associated with women’s preferred family size. However, when the woman has higher education than her mother-in-law, her preferred family size gets smaller, suggesting that education provides women with greater autonomy in their decision-making on childbearing

Social cohesion through football: a quasi-experimental mixed methods design to evaluate a complex health promotion program

Social isolation and disengagement fragments local communities. Evidence indicates that refugee families are highly vulnerable to social isolation in their countries of resettlement. Research to identify approaches to best address this is needed. Football United is a program that aims to foster social inclusion and cohesion in areas with high refugee settlement in New South Wales, Australia, through skills and leadership development, mentoring, and the creation of links with local community and corporate leaders and organisations. The Social Cohesion through Football study’s broad goal is to examine the implementation of a complex health promotion program, and to analyse the processes involved in program implementation. The study will consider program impact on individual health and wellbeing, social inclusion and cohesion, as well as analyse how the program by necessity interacts and adapts to context during implementation, a concept we refer to as plasticity. The proposed study will be the first prospective cohort impact study to our knowledge to assess the impact of a comprehensive integrated program using football as a vehicle for fostering social inclusion and cohesion in communities with high refugee settlement

Childhood febrile illness and the risk of myopia in UK Biobank participants

Purpose Historical reports suggest febrile illness during childhood is a risk factor for myopia. The establishment of the UK Biobank provided a unique opportunity to investigate this relationship. Patients and methods We studied a sample of UK Biobank participants of White ethnicity aged 40–69 years old who underwent autorefraction (N=91 592) and were classified as myopic (≤−0.75 Dioptres (D)), highly myopic (≤−6.00 D), or non-myopic (>−0.75 D). Self-reported age at diagnosis of past medical conditions was ascertained during an interview with a nurse at a Biobank assessment centre. Logistic regression analysis was used to calculate the odds ratio (OR) for myopia or high myopia associated with a diagnosis before age 17 years of each of nine febrile illnesses, after adjusting for potential confounders (age, sex, highest educational qualification, and birth order). Results Rubella, mumps, and pertussis were associated with myopia: rubella, OR=1.38, 95% CI: 1.03–1.85, P=0.030; mumps, OR=1.32, 95% CI: 1.07–1.64, P=0.010; and pertussis, OR=1.39, 95% CI 1.03–1.87, P=0.029. Measles, rubella, and pertussis were associated with high myopia: measles, OR=1.48, 95% CI: 1.07–2.07, P=0.019; rubella, OR=1.94, 95% CI: 1.12–3.35, P=0.017; and pertussis, OR=2.15, 95% CI: 1.24–3.71, P=0.006. The evidence did not support an interaction between education and febrile illness in explaining the above risks. Conclusion A history of childhood measles, rubella, or pertussis was associated with high myopia, whereas a history of childhood rubella, mumps, or pertussis was associated with any myopia. The reasons for these associations are unclear

Expression and localization of estrogen receptor-alpha protein in normal and abnormal term placentae and stimulation of trophoblast differentiation by estradiol

Estrogens play an important role in the regulation of placental function, and 17-beta-estradiol (E2) production rises eighty fold during human pregnancy. Although term placenta has been found to specifically bind estrogens, cellular localization of estrogen receptor alpha (ER-alpha) in trophoblast remains unclear. We used western blot analysis and immunohistochemistry with h-151 and ID5 monoclonal antibodies to determine the expression and cellular localization of ER-alpha protein in human placentae and cultured trophoblast cells. Western blot analysis revealed a ~65 kDa ER-alpha band in MCF-7 breast carcinoma cells (positive control). A similar band was detected in five normal term placentae exhibiting strong expression of Thy-1 differentiation protein in the villous core. However, five other term placentae, which exhibited low or no Thy-1 expression (abnormal placentae), exhibited virtually no ER-alpha expression. In normal placentae, nuclear ER-alpha expression was confined to villous cytotrophoblast cells (CT), but syncytiotrophoblast (ST) and extravillous trophoblast cells were unstained. In abnormal placentae no CT expressing ER-alpha were detected. Normal and abnormal placentae also showed ER-alpha expression in villous vascular pericytes and amniotic (but not villous) fibroblasts; no staining was detected in amniotic epithelial cells or decidual cells. All cultured trophoblast cells derived from the same normal and abnormal placentae showed distinct ER-alpha expression in western blots, and the ER-alpha expression was confined to the differentiating CT, but not to the mature ST. Trophoblast cells from six additional placentae were cultured in normal medium with phenol red (a weak estrogen) as above (PhR+), or plated in phenol red-free medium (PhR-) without or with mid-pregnancy levels of E2 (20 nM). Culture in PhR- medium without E2 caused retardation of syncytium formation and PhR-medium with E2 caused acceleration of syncytium formation compared to cultures in PhR+ medium. These data indicate that the considerable increase in estrogen production during pregnancy may play a role, via the ER-alpha, in the stimulation of CT differentiation and promote function in normal placentae. This mechanism, however, may not operate in abnormal placentae, which show a lack of ER-alpha expression

Cellular dissection of psoriasis for transcriptome analyses and the post-GWAS era

Abstract Background Genome-scale studies of psoriasis have been used to identify genes of potential relevance to disease mechanisms. For many identified genes, however, the cell type mediating disease activity is uncertain, which has limited our ability to design gene functional studies based on genomic findings. Methods We identified differentially expressed genes (DEGs) with altered expression in psoriasis lesions (n = 216 patients), as well as candidate genes near susceptibility loci from psoriasis GWAS studies. These gene sets were characterized based upon their expression across 10 cell types present in psoriasis lesions. Susceptibility-associated variation at intergenic (non-coding) loci was evaluated to identify sites of allele-specific transcription factor binding. Results Half of DEGs showed highest expression in skin cells, although the dominant cell type differed between psoriasis-increased DEGs (keratinocytes, 35%) and psoriasis-decreased DEGs (fibroblasts, 33%). In contrast, psoriasis GWAS candidates tended to have highest expression in immune cells (71%), with a significant fraction showing maximal expression in neutrophils (24%, P < 0.001). By identifying candidate cell types for genes near susceptibility loci, we could identify and prioritize SNPs at which susceptibility variants are predicted to influence transcription factor binding. This led to the identification of potentially causal (non-coding) SNPs for which susceptibility variants influence binding of AP-1, NF-κB, IRF1, STAT3 and STAT4. Conclusions These findings underscore the role of innate immunity in psoriasis and highlight neutrophils as a cell type linked with pathogenetic mechanisms. Assignment of candidate cell types to genes emerging from GWAS studies provides a first step towards functional analysis, and we have proposed an approach for generating hypotheses to explain GWAS hits at intergenic loci.http://deepblue.lib.umich.edu/bitstream/2027.42/109537/1/12920_2013_Article_485.pd

Balancing repair and tolerance of DNA damage caused by alkylating agents

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity

Translational toxicology in setting occupational exposure limits for dusts and hazard classification – a critical evaluation of a recent approach to translate dust overload findings from rats to humans

Background We analyze the scientific basis and methodology used by the German MAK Commission in their recommendations for exposure limits and carcinogen classification of “granular biopersistent particles without known specific toxicity” (GBS). These recommendations are under review at the European Union level. We examine the scientific assumptions in an attempt to reproduce the results. MAK’s human equivalent concentrations (HECs) are based on a particle mass and on a volumetric model in which results from rat inhalation studies are translated to derive occupational exposure limits (OELs) and a carcinogen classification. Methods We followed the methods as proposed by the MAK Commission and Pauluhn 2011. We also examined key assumptions in the metrics, such as surface area of the human lung, deposition fractions of inhaled dusts, human clearance rates; and risk of lung cancer among workers, presumed to have some potential for lung overload, the physiological condition in rats associated with an increase in lung cancer risk. Results The MAK recommendations on exposure limits for GBS have numerous incorrect assumptions that adversely affect the final results. The procedures to derive the respirable occupational exposure limit (OEL) could not be reproduced, a finding raising considerable scientific uncertainty about the reliability of the recommendations. Moreover, the scientific basis of using the rat model is confounded by the fact that rats and humans show different cellular responses to inhaled particles as demonstrated by bronchoalveolar lavage (BAL) studies in both species. Conclusion Classifying all GBS as carcinogenic to humans based on rat inhalation studies in which lung overload leads to chronic inflammation and cancer is inappropriate. Studies of workers, who have been exposed to relevant levels of dust, have not indicated an increase in lung cancer risk. Using the methods proposed by the MAK, we were unable to reproduce the OEL for GBS recommended by the Commission, but identified substantial errors in the models. Considerable shortcomings in the use of lung surface area, clearance rates, deposition fractions; as well as using the mass and volumetric metrics as opposed to the particle surface area metric limit the scientific reliability of the proposed GBS OEL and carcinogen classification.International Carbon Black Associatio