Polymorphism in TGFB1 is associated with worse non-relapse mortality and overall survival after stem cell transplantation with unrelated donors.

Transforming growth factor beta-1, encoded by the TGFB1 gene, is a cytokine that plays a central role in many physiological and pathogenic processes. We have sequenced TGFB1 regulatory region and assigned allelic genotypes in a large cohort of hematopoietic stem cell transplantation patients and donors. In this study, we analyzed 522 unrelated donor-patient pairs and examined the combined effect of all the common polymorphisms in this genomic region. In univariate analysis, we found that patients carrying a specific allele, 'p001', showed significantly reduced overall survival (5-year overall survival 30.7% for p001/ p001 patients vs. 41.6% others; P=0.032) and increased non-relapse mortality (1-year nonrelapse mortality: 39.0% vs. 25.4%; P=0.039) after transplantation. In multivariate analysis, the presence of a p001/ p001 genotype in patients was confirmed as an independent factor for reduced overall survival [hazard ratio=1.53 (1.04-2.24); P=0.031], and increased non-relapse mortality [hazard ratio=1.73 (1.06-2.83); P=0.030]. In functional experiments we found a trend towards a higher percentage of surface transforming growth factor beta-1-positive regulatory T cells after activation when the cells had a p001 allele (P=0.07). Higher or lower production of transforming growth factor beta-1 in the inflammatory context of hematopoietic stem cell transplantation may influence the development of complications in these patients. Findings indicate that TGFB1 genotype could potentially be of use as a prognostic factor in hematopoietic stem cell transplantation risk assessment algorithms

Walking into the Footprint of EU Law: Unpacking the Gendered Consequences of Brexit

This article explores the gendered nature of the process of withdrawing from the European Union. Considering the EU is widely accepted as a gender actor, particularly in the context of employment policy, the marginality of these issues in current debates reflects a hierarchy in the value attributed to different policy areas that crystallizes the high-low politics binary. European led initiatives have undoubtedly changed the nature of equality policies in the Member States. Recent studies have also outlined how, and to what extent, EU policy contributes to shifts in gender regimes, gender policy and gender relations at the national level. Women in the UK have benefited greatly from membership of the EU/EEC, thus looking at Brexit as a process provides a unique opportunity to reflect on the relationship, and patterns of influence, between European and national legislation

Recurrent rare copy number variants increase risk for esotropia

Purpose: To determine whether rare copy number variants (CNVs) increase risk for comitant esotropia. Methods: CNVs were identified in 1614 Caucasian individuals with comitant esotropia and 3922 Caucasian controls from Illumina SNP genotyping using two Hidden Markov model (HMM) algorithms, PennCNV and QuantiSNP, which call CNVs based on logR ratio and B allele frequency. Deletions and duplications greater than 10 kb were included. Common CNVs were excluded. Association testing was performed with 1 million permutations in PLINK. Significant CNVs were confirmed with digital droplet polymerase chain reaction (ddPCR). Whole genome sequencing was performed to determine insertion location and breakpoints. Results: Esotropia patients have similar rates and proportions of CNVs compared with controls but greater total length and average size of both deletions and duplications. Three recurrent rare duplications significantly (P = 1 × 10-6) increase the risk of esotropia: chromosome 2p11.2 (hg19, 2:87428677-87965359), spanning one long noncoding RNA (lncRNA) and two microRNAs (OR 14.16; 95% confidence interval [CI] 5.4-38.1); chromosome 4p15.2 (hg19, 4:25554332-25577184), spanning one lncRNA (OR 11.1; 95% CI 4.6-25.2); chromosome 10q11.22 (hg19, 10:47049547-47703870) spanning seven protein-coding genes, one lncRNA, and four pseudogenes (OR 8.96; 95% CI 5.4-14.9). Overall, 114 cases (7%) and only 28 controls (0.7%) had one of the three rare duplications. No case nor control had more than one of these three duplications. Conclusions: Rare CNVs are a source of genetic variation that contribute to the genetic risk for comitant esotropia, which is likely polygenic. Future research into the functional consequences of these recurrent duplications may shed light on the pathophysiology of esotropia

Social sciences research in neglected tropical diseases 2: A bibliographic analysis

The official published version of the article can be found at the link below.Background There are strong arguments for social science and interdisciplinary research in the neglected tropical diseases. These diseases represent a rich and dynamic interplay between vector, host, and pathogen which occurs within social, physical and biological contexts. The overwhelming sense, however, is that neglected tropical diseases research is a biomedical endeavour largely excluding the social sciences. The purpose of this review is to provide a baseline for discussing the quantum and nature of the science that is being conducted, and the extent to which the social sciences are a part of that. Methods A bibliographic analysis was conducted of neglected tropical diseases related research papers published over the past 10 years in biomedical and social sciences. The analysis had textual and bibliometric facets, and focussed on chikungunya, dengue, visceral leishmaniasis, and onchocerciasis. Results There is substantial variation in the number of publications associated with each disease. The proportion of the research that is social science based appears remarkably consistent (<4%). A textual analysis, however, reveals a degree of misclassification by the abstracting service where a surprising proportion of the "social sciences" research was pure clinical research. Much of the social sciences research also tends to be "hand maiden" research focused on the implementation of biomedical solutions. Conclusion There is little evidence that scientists pay any attention to the complex social, cultural, biological, and environmental dynamic involved in human pathogenesis. There is little investigator driven social science and a poor presence of interdisciplinary science. The research needs more sophisticated funders and priority setters who are not beguiled by uncritical biomedical promises

Gender and Administration

Summary Public administration in development has been a poor instrument for implementing gender policies. Rural development administration in particular has tended to be indifferently accountable to female ‘publics’ in agrarian economies. Conventionally, this particular feature of institutional failure is explained by the suggestion that public administrations reflect gender relations in society. This paper, however, argues that the role of public administration in the organization of gender provokes questions about the gender of organization. It sketches out the conceptual premises for a theory of the gender of organization, looking at the way organizational structures, cultures, and purposes institutionalize male dominance. This perspective may help illuminate the processes and relationships through which other inequalities, such as those of class, race, and the North?South divide, are reproduced in public administration. Résumé Le Genre et l'insuccès des institutions dans le développement: l'organisation du Genre et le Genre dans l'organisation Au sein du développement, les administrations publiques ont constitué un outil peu utile pour la mise en oeuvre des politiques relatives au genre. Les administrations de développement rural notamment ont eu tendance à comptabiliser de manière indifférente les ‘publics’ féminins dans les économies agraires. Classiquement, et notoirement, cette caractéristique de l'insuccès des institutions est expliquée par la suggestion que les administrations publiques reflètent les rapports entre les genres dans la société. Le présent article, par contre, revendique que le rôle des administrations publiques dans l'organisation des genres soulève certaines questions le genre dans l'organisation même. L'auteur ébauche les prémisses d'une éventuelle théorie du genre dans l'organisation, et examine comment les structures, les cultures et les objectifs mêmes de ces organisations tendent à institutionnaliser la dominance masculine. Cette perspective veut aider à mettre en lumière des procédés et des rapports par l'influence desquels d'autres inégalités, par exemples celles des classes, des races et du partage nord?sud, viennent à se reproduire dans les administrations publiques. Resumen El Género y las fallas institucionales en el desarrollo: la organización del género y el género de la organización La administración pública en el desarrollo ha sido un instrumento muy pobre para la implementación de criterios relativos al género. En las economías agrarias en particular la administración del desarrollo rural tiende a ser poco responsable para con el ‘público’ femenino. Tradicionalmente, este rasgo característico del fracaso institucional se explica sugiriendo que la administración pública refleja las relaciones entre los sexos en la sociedad. Este artículo, sin embargo, argumenta que el papel de la administración pública en la organización del género suscita interrogantes sobre el género de la organización. Se bosquejan las premisas conceptuales para una teoría del género en la organización, analizando la forma en que las culturas, estructuras organizativas y objetivos institucionalizan la dominación masculina. Esta perspectiva puede arrojar luz sobre los procesos y relaciones a través de los cuales otras desigualdades — clase, raza, la división Norte?Sur — se reproducen en la administración pública

Reciprocal Relations Between Emotional Self-Efficacy Beliefs and Ego-Resiliency Across Time

The present study examined the longitudinal relations of adolescents' self-reported ego-resiliency to their emotional self-efficacy beliefs in expressing positive emotions and in managing negative emotions as they moved into early adulthood. Participants were 239 females and 211 males with a mean age of 17 years (SD = .80) at T1, 19 years (SD = .80) at T2, 21 years (SD = .82) at T3, and 25 years (SD = .80) at T4. A four-wave cross-lagged regression model and mediational analyses were used. In a panel structural equation model controlling for the stability of the constructs, reciprocal relationships across time were found between ego-resiliency and emotional self-efficacy beliefs related to the expression of positive emotions and to the management of negative emotions. Moreover, the relation between ego-resiliency assessed at T1 and T3, and ego-resiliency assessed at T2 and T4, was mediated through emotional self-efficacy beliefs (at T2 and T3, respectively), and vice versa. The posited conceptual model accounted for a significant portion of variance in ego-resiliency and has implications for understanding the development of ego-resiliency

‘The Coaching Needs of High Performance Female Athletes within the Coach-Athlete Dyad’

Within the research literature there is little work that has examined how coaches (and coaching) can positively influence female athletes’ continued participation and development in performance sport. With this in mind, utilising a grounded theory approach, this study focused on what are the coaching preferences of female athletes within the elite coachathlete dyad. Through interviews with 27 current high performance female athletes, four major coaching needs were found. These were: to be supported as person as well a performer, coaching to be a joint endeavour, the need for positive communication and finally, recognition of the salience of gender within the coach-athlete dyad. The findings provide evidence that the relational expertise of coaches is at the forefront of these women’s coaching needs. This study also demonstrates that for the participants, the coach-athlete relationship is at the heart of improving athletic training and performance, and that gender is an important influence on this relationship. Furthermore, the research highlights the strength of using an interpretive-qualitative paradigmatic approach to athlete preferences through foregrounding the women’s voices and experiences

Membrane curvature at a glance

Membrane curvature is an important parameter in defining the morphology of cells, organelles and local membrane subdomains. Transport intermediates have simpler shapes, being either spheres or tubules. The generation and maintenance of curvature is of central importance for maintaining trafficking and cellular functions. It is possible that local shapes in complex membranes could help to define local subregions. In this Cell Science at a Glance article and accompanying poster, we summarize how generating, sensing and maintaining high local membrane curvature is an active process that is mediated and controlled by specialized proteins using general mechanisms: (i) changes in lipid composition and asymmetry, (ii) partitioning of shaped transmembrane domains of integral membrane proteins or protein or domain crowding, (iii) reversible insertion of hydrophobic protein motifs, (iv) nanoscopic scaffolding by oligomerized hydrophilic protein domains and, finally, (v) macroscopic scaffolding by the cytoskeleton with forces generated by polymerization and by molecular motors. We also summarize some of the discoveries about the functions of membrane curvature, where in addition to providing cell or organelle shape, local curvature can affect processes like membrane scission and fusion as well as protein concentration and enzyme activation on membranes