Androgen stimulates growth of mouse preantral follicles in vitro: Interaction with follicle-stimulating hormone and with growth factors of the TGFβ super family

Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aim of investigating interaction with follicle-stimulating hormone (FSH), the steroidogenic pathway, and growth factors of the TGFβ superfamily that are known to have a role in early follicle development. Both testosterone and DHT stimulated follicle growth and augmented FSH-induced growth and increased the incidence of antrum formation among the granulosa cell layers of these preantral follicles after 72 hours in culture. Effects of both androgens were reversed by the androgen receptor antagonist flutamide. FSH receptor expression was increased in response to both testosterone and DHT, as was that of Star, whereas Cyp11a1 was down-regulated. The key androgeninduced changes in the TGFβ signaling pathway were down-regulation of Amh, Bmp15, and their receptors. Inhibition of Alk6 (Bmpr1b), a putative partner for Amhr2 and Bmpr2, by dorsomorphin resulted in augmentation of androgen-stimulated growth and modification of androgen-induced gene expression. Our findings point to varied effects of androgen on preantral follicle growth and function, including interaction with FSH-activated growth and steroidogenesis, and, importantly, implicate the intrafollicular TGFb systemas a keymediator of androgen action. These findings provide insight into abnormal early follicle development in PCOS

Spatiotemporal distribution and population at risk of soil-transmitted helminth infections following an eight-year school-based deworming programme in Burundi, 2007-2014

Background: Investigating the effect of successive annual deworming rounds on the spatiotemporal distribution of infection prevalence and numbers at risk for soil-transmitted helminths (STHs) can help identify communities nearing elimination and those needing further interventions. In this study, we aim to quantify the impact of an 8-year mass drug administration (MDA) programme (from 2007 to 2014) on the spatiotemporal distribution of prevalence of STH infections and to estimate the number of school-aged children infected with STHs in Burundi. Methods: During annual longitudinal school-based surveys in Burundi between 2007 and 2011, STH infection and anthropometric data for a total of 40,656 children were collected; these data were supplemented with data from a national survey conducted in 2014. Bayesian model based geostatistics (MBG) were used to generate predictive prevalence maps for each STH species and year. The numbers of children at-risk of infection per district between 2008 and 2014 were estimated as the product of the predictive prevalence maps and population density maps. Results: Overall, the degree of spatial clustering of STH infections decreased between 2008 and 2011; in 2014 the geographical clusters of all STH infections reappeared. The reduction in prevalence was small for Ascaris lumbricoides and Trichuris trichiura in the centre and central north of the country. Our predictive prevalence maps for hookworm indicate a reduction in prevalence along the periphery of the country. The predicted number of children infected with any STH species decreased substantially between 2007 and 2011, but in 2014 there was an increase in the predicted number of children infected with A. lumbricoides and T. trichiura. In 2014, the districts with the highest predicted number of children infected with A. lumbricoides, T. trichiura and hookworms were Kibuye district (n = 128,903), Mabayi district (n = 35,302) and Kiremba (n = 87,511), respectively. Conclusions: While the MDA programme in Burundi resulted in a reduction in STH prevalence, this reduction was spatiotemporally heterogeneous, with some pockets of high prevalence remaining, suggesting that treatment coverage and complementary interventions should be evaluated to improve impact.The reported monitoring and evaluation programme was financially supported by Geneva Global and the Global Network for Tropical Diseases (GNTD) in collaboration with the Sabine Institute, and by the Schistosomiasis Control Initiative, which provided also technical assistance. The reported national mapping survey conducted in 2014 was funded by the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) and Schistosomiasis Control Initiative

Cost-effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts: economic evaluation alongside a randomised controlled trial (EVerT trial)

Background Plantar warts (verrucae) are extremely common. Although many will spontaneously disappear without treatment, treatment may be sought for a variety of reasons such as discomfort. There are a number of different treatments for cutaneous warts, with salicylic acid and cryotherapy using liquid nitrogen being two of the most common forms of treatment. To date, no full economic evaluation of either salicylic acid or cryotherapy has been conducted based on the use of primary data in a pragmatic setting. This paper describes the cost-effectiveness analysis which was conducted alongside a pragmatic multicentre, randomised trial evaluating the clinical effectiveness of cryotherapy versus 50% salicylic acid of the treatment of plantar warts. Methods A cost-effectiveness analysis was undertaken alongside a pragmatic multicentre, randomised controlled trial assessing the clinical effectiveness of 50% salicylic acid and cryotherapy using liquid nitrogen at 12 weeks after randomisation of patients. Cost-effectiveness outcomes were expressed as the additional cost required to completely cure the plantar warts of one additional patient. A NHS perspective was taken for the analysis. Results Cryotherapy costs on average £101.17 (bias corrected and accelerated (BCA) 95% CI: 85.09-117.26) more per participant over the 12 week time-frame, while there is no additional benefit, in terms of proportion of patients healed compared with salicylic acid. Conclusions Cryotherapy is more costly and no more effective than salicylic acid

Teacher agency in curriculum making: agents of change and spaces for manoeuvre

In the wake of new forms of curricular policy in many parts of the world, teachers are increasingly required to act as agents of change. And yet, teacher agency is under-theorised and often misconstrued in the educational change literature, wherein agency and change are seen as synonymous and positive. This paper addresses the issue of teacher agency in the context of an empirical study of curriculum making in schooling. Drawing upon the existing literature, we outline an ecological view of agency as an effect. These insights frame the analysis of a set of empirical data, derived from a research project about curriculum-making in a school and further education college in Scotland. Based upon the evidence, we argue that the extent to which teachers are able to achieve agency varies from context to context based upon certain environmental conditions of possibility and constraint, and that an important factor in this lies in the beliefs, values and attributes that teachers mobilise in relation to particular situations

Cost-Effectiveness of a Telephone-Delivered Intervention for Physical Activity and Diet

Background: Given escalating rates of chronic disease, broad-reach and cost-effective interventions to increase physical activity and improve dietary intake are needed. The cost-effectiveness of a Telephone Counselling intervention to improve physical activity and diet, targeting adults with established chronic diseases in a low socio-economic area of a major Australian city was examined. Methodology/Principal Findings: A cost-effectiveness modelling study using data collected between February 2005 and November 2007 from a cluster-randomised trial that compared Telephone Counselling with a “Usual Care” (brief intervention) alternative. Economic outcomes were assessed using a state-transition Markov model, which predicted the progress of participants through five health states relating to physical activity and dietary improvement, for ten years after recruitment. The costs and health benefits of Telephone Counselling, Usual Care and an existing practice (Real Control) group were compared. Telephone Counselling compared to Usual Care was not cost-effective ($78,489 per quality adjusted life year gained). However, the Usual Care group did not represent existing practice and is not a useful comparator for decision making. Comparing Telephone Counselling outcomes to existing practice (Real Control), the intervention was found to be cost-effective ($29,375 per quality adjusted life year gained). Usual Care (brief intervention) compared to existing practice (Real Control) was also cost-effective ($12,153 per quality adjusted life year gained). Conclusions/Significance: This modelling study shows that a decision to adopt a Telephone Counselling program over existing practice (Real Control) is likely to be cost-effective. Choosing the ‘Usual Care’ brief intervention over existing practice (Real Control) shows a lower cost per quality adjusted life year, but the lack of supporting evidence for efficacy or sustainability is an important consideration for decision makers. The economics of behavioural approaches to improving health must be made explicit if decision makers are to be convinced that allocating resources toward such programs is worthwhile

The Pinochet case : cosmopolitanism and intermestic human rights

This article explores the Pinochet case, widely heralded as a landmark, as a case of ‘intermestic’ human rights that raises difficult normative and empirical questions concerning cosmopolitan justice. The article is a contribution to the sociology of human rights from the perspective of methodological cosmopolitanism, developing conceptual tools and methods to study how cosmopolitanising state institutions and cultural norms are inter-related. The argument is made that in order to understand issues of cosmopolitan justice, sociologists must give more consideration to political culture

The CIPRUS study, a nurse-led psychological treatment for patients with undifferentiated somatoform disorder in primary care: study protocol for a randomised controlled trial

Background: Up to a third of patients presenting medically unexplained physical symptoms in primary care may have a somatoform disorder, of which undifferentiated somatoform disorder (USD) is the most common type. Psychological interventions can reduce symptoms associated with USD and improve functioning. Previous research has either been conducted in secondary care or interventions have been provided by general practitioners (GPs) or psychologists in primary care. As efficiency and cost-effectiveness are imperative in primary care, it is important to investigate whether nurse-led interventions are effective as well. The aim of this study is to examine the effectiveness and cost-effectiveness of a short cognitive behavioural therapy (CBT)-based treatment for patients with USD provided by mental health nurse practitioners (MHNPs), compared to usual care. Methods: In a cluster randomised controlled trial, 212 adult patients with USD will be assigned to the intervention or care as usual. The intervention group will be offered a short, individual CBT-based treatment by the MHNP in addition to usual GP care. The main goal of the intervention is that patients become less impaired by their physical symptoms and cope with symptoms in a more effective way. In six sessions patients will receive problem-solving treatment. The primary outcome is improvement in physical functioning, measured by the physical component summary score of the RAND-36. Secondary outcomes include health-related quality of life measured by the separate subscales of the RAND-36, somatization (PHQ-15) and symptoms of depression and anxiety (HADS). Problem-solving skills, health anxiety, illness perceptions, coping, mastery and working alliance will be assessed as potential mediators. Assessments will be done at 0, 2, 4, 8 and 12 months. An economic evaluation will be conducted from a societal perspective with quality of life as the primary outcome measure assessed by the EQ-5D-5L. Health care, patient and lost productivity costs will be assessed with the Tic-P. Discussion: We expect that the intervention will improve physical functioning and is cost-effective compared to usual care. If so, more patients might successfully be treated in general practice, decreasing the number of referrals to specialist care. Trial registration: Dutch Trial Registry, identifier: NTR4686, Registered on 14 July 2014. © 2017 The Author(s)