Patterns and Practices of Women\u27s Leadership in the Yorkshire Quaker Community, 1760-1820

By the second half of the eighteenth century, women ministers had become the principal upholders of the spiritual life of Quakerism in Yorkshire. Drawing on a range of sources including the institutional records of Quaker Meetings, personal correspondence and spiritual journals and autobiographies, this paper aims to shed light on the precise nature of female leadership in the Religious Society of Friends and to contribute to greater understanding of the conditions under which it became dominant. It suggests that the growing tendency for women to outnumber men as ministers was closely linked to wider social and economic trends within contemporary Quakerism, and highlights the importance of family ties and support networks of kinship and friendship in underpinning women\u27s exercise of ministering responsibilities

Diethylcarbamazine activity against Brugia malayi microfilariae is dependent on inducible nitric-oxide synthase and the cyclooxygenase pathway

BACKGROUND: Diethylcarbamazine (DEC) has been used for many years in the treatment of human lymphatic filariasis. Its mode of action is not well understood, but it is known to interact with the arachidonic acid pathway. Here we have investigated the contribution of the nitric oxide and cyclooxygenase (COX) pathways to the activity of DEC against B. malayi microfilariae in mice. METHODS: B. malayi microfilariae were injected intravenously into mice and parasitaemia was measured 24 hours later. DEC was then administered to BALB/c mice with and without pre-treatment with indomethacin or dexamethasone and the parasitaemia monitored. To investigate a role for inducible nitric oxide in DEC's activity, DEC and ivermectin were administered to microfilaraemic iNOS(-/- )mice and their background strain (129/SV). Western blot analysis was used to determine any effect of DEC on the production of COX and inducible nitric-oxide synthase (iNOS) proteins. RESULTS: DEC administered alone to BALB/c mice resulted in a rapid and profound reduction in circulating microfilariae within five minutes of treatment. Microfilarial levels began to recover after 24 hours and returned to near pre-treatment levels two weeks later, suggesting that the sequestration of microfilariae occurs independently of parasite killing. Pre-treatment of animals with dexamethasone or indomethacin reduced DEC's efficacy by almost 90% or 56%, respectively, supporting a role for the arachidonic acid and cyclooxygenase pathways in vivo. Furthermore, experiments showed that treatment with DEC results in a reduction in the amount of COX-1 protein in peritoneal exudate cells. Additionally, in iNOS(-/- )mice infected with B. malayi microfilariae, DEC showed no activity, whereas the efficacy of another antifilarial drug, ivermectin, was unaffected. CONCLUSION: These results confirm the important role of the arachidonic acid metabolic pathway in DEC's mechanism of action in vivo and show that in addition to its effects on the 5-lipoxygenase pathway, it targets the cyclooxygenase pathway and COX-1. Moreover, we show for the first time that inducible nitric oxide is essential for the rapid sequestration of microfilariae by DEC

The role of alcohol in constructing gender & class identities among young women in the age of social media

Research suggests young women view drinking as a pleasurable aspect of their social lives but that they face challenges in engaging in a traditionally ‘masculine’ behaviour whilst maintaining a desirable ‘femininity’. Social network sites such as Facebook make socialising visible to a wide audience. This paper explores how young people discuss young women’s drinking practices, and how young women construct their identities through alcohol consumption and its display on social media. We conducted 21 friendship-based focus groups (both mixed and single sex) with young adults aged 18–29 years and 13 individual interviews with a subset of focus group respondents centred on their Facebook practices. We recruited a purposive sample in Glasgow, Scotland (UK) which included ‘middle class’ (defined as students and those in professional jobs) and ‘working class’ respondents (employed in manual/service sector jobs), who participated in a range of venues in the night time economy. Young women’s discussions revealed a difficult ‘balancing act’ between demonstrating an ‘up for it’ sexy (but not too sexy) femininity through their drinking and appearance, while still retaining control and respectability. This ‘balancing act’ was particularly precarious for working class women, who appeared to be judged more harshly than middle class women both online and offline. While a gendered double standard around appearance and alcohol consumption is not new, a wider online audience can now observe and comment on how women look and behave. Social structures such as gender and social class remain central to the construction of identity both online and offline

Increased orthogeriatrician involvement in hip fracture care and its impact on mortality in England

Objectives to describe the increase in orthogeriatrician involvement in hip fracture care in England and its association with improvements in time to surgery and mortality. Study design analysis of Hospital Episode Statistics for 196,401 patients presenting with hip fracture to 150 hospitals in England between 1 April 2010 and 28 February 2014, combined with data on orthogeriatrician hours from a national organisational survey. Methods we examined changes in the average number of hours worked by orthogeriatricians in orthopaedic departments per patient with hip fracture, and their potential effect on mortality within 30 days of presentation. The role of prompt surgery (on day of or day after presentation) was explored as a potential confounding factor. Associations were assessed using conditional Poisson regression models with adjustment for patients’ sex, age and comorbidity and year, with hospitals treated as fixed effects. Results between 2010 and 2013, there was an increase of 2.5 hours per patient in the median number of hours worked by orthogeriatricians—from 1.5 to 4.0 hours. An increase of 2.5 hours per patient was associated with a relative reduction in mortality of 3.4% (95% confidence interval 0.9% to 5.9%, P = 0.01). This corresponds to an absolute reduction of approximately 0.3%. Higher numbers of orthogeriatrician hours were associated with higher rates of prompt surgery, but were independently associated with lower mortality. Conclusion in the context of initiatives to improve hip fracture care, we identified statistically significant and robust associations between increased orthogeriatrician hours per patient and reduced 30-day mortality

The effectiveness of health appraisal processes currently in addressing health and wellbeing during spatial plan appraisal: a systematic review

<p>Abstract</p> <p>Background</p> <p>Spatial planning affects the built environment, which in turn has the potential to have a significant impact on health, for good or ill. One way of ensuring that spatial plans take due account of health is through the inclusion of health considerations in the statutory and non statutory appraisal processes linked to plan-making processes.</p> <p>Methods</p> <p>A systematic review to identify evaluation studies of appraisals or assessments of plans where health issues were considered from 1987 to 2010.</p> <p>Results</p> <p>A total of 6161 citations were identified: 6069 from electronic databases, 57 fromwebsite searches, with a further 35 citations from grey literature, of which 20 met the inclusion criteria. These 20 citations reported on a total of 135 different case studies: 11 UK HIA; 11 non UK high income countries HIA, 5 UK SEA or other integrated appraisal; 108 non UK high income SEA or other integrated appraisal. All studies were in English. No relevant studies were identified reporting on low or middle income countries.</p> <p>The studies were limited by potential bias (no independent evaluation, with those undertaking the appraisal also responsible for reporting outcomes), lack of detail and a lack of triangulation of results. Health impact assessments generally covered the four specified health domains (physical activity, mental health and wellbeing, environmental health issues such as pollution and noise, injury) more comprehensively than SEA or other integrated appraisals, although mental health and wellbeing was an underdeveloped area. There was no evidence available on the incorporation of health in Sustainability Appraisal, limited evidence that the recommendations from any type of appraisal were implemented, and almost no evidence that the recommendations had led to the anticipated outcomes or improvements in health postulated.</p> <p>Conclusion</p> <p>Research is needed to assess (i) the degree to which statutory plan appraisal processes (SA in the UK) incorporate health; (ii) whether recommendations arising from health appraisal translate into the development process and (iii) whether outcomes are as anticipated.</p

The relationship between salivary C-reactive protein and cognitive function in children aged 11-14 years: Does psychopathology have a moderating effect?

Elevated C-reactive protein (CRP), a non-specific biomarker of systemic bodily inflammation, has been associated with more pronounced cognitive impairments in adults with psychiatric disorders, particularly in the domains of memory and executive function. Whether this association is present in early life (i.e., the time at which the cognitive impairments that characterise these disorders become evident), and is specific to those with emerging psychiatric disorders, has yet to be investigated. To this end, we examined the association between salivary CRP and cognitive function in children aged 11- 14 years and explored the moderating effect of psychopathology. The study utilised data from an established longitudinal investigation of children recruited from the community (N=107) that had purposively over-sampled individuals experiencing psychopathology (determined using questionnaires). CRP was measured in saliva samples and participants completed assessments of cognition (memory and executive function) and psychopathology (internalising and externalising symptoms and psychotic-like experiences). Linear regression models indicated that higher salivary CRP was associated with poorer letter fluency (β=-0.24, p=0.006) and scores on the inhibition (β=-0.28, p=0.004) and inhibition/switching (β=-0.36, p<0.001) subtests of the colour-word interference test, but not with performance on any of the memory tasks (working, visual, and verbal memory tasks). Results were largely unchanged after adjustment for psychopathology and no significant interactions between CRP and psychopathology were observed on any cognitive measure. Our findings provide preliminary evidence that elevated salivary CRP is associated with poorer cognitive function in early life, but that this association is not moderated by concurrent psychopathology. These findings have implications for early intervention strategies that attempt to ameliorate cognitive deficits associated with emerging psychiatric disorders. Further research is needed to determine whether salivary CRP levels can be used as a valid marker of peripheral inflammation among healthy adolescents

Comparability: manufacturing, characterization and controls, report of a UK Regenerative Medicine Platform Pluripotent Stem Cell Platform Workshop, Trinity Hall, Cambridge, 14–15 September 2015

This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this ‘may be difficult for cell-based medicinal products’. Therefore a well-managed change process is required which needs access to good science and regulatory advice and developers are encouraged to seek help early. The workshop shared current thinking and best practice and allowed the definition of key research questions. The intent of this report is to summarize the key issues and the consensus reached on each of these by the expert delegates

Industrial scale high-throughput screening delivers multiple fast acting macrofilaricides.

Nematodes causing lymphatic filariasis and onchocerciasis rely on their bacterial endosymbiont, Wolbachia, for survival and fecundity, making Wolbachia a promising therapeutic target. Here we perform a high-throughput screen of AstraZeneca's 1.3 million in-house compound library and identify 5 novel chemotypes with faster in vitro kill rates (<2 days) than existing anti-Wolbachia drugs that cure onchocerciasis and lymphatic filariasis. This industrial scale anthelmintic neglected tropical disease (NTD) screening campaign is the result of a partnership between the Anti-Wolbachia consortium (A∙WOL) and AstraZeneca. The campaign was informed throughout by rational prioritisation and triage of compounds using cheminformatics to balance chemical diversity and drug like properties reducing the chance of attrition from the outset. Ongoing development of these multiple chemotypes, all with superior time-kill kinetics than registered antibiotics with anti-Wolbachia activity, has the potential to improve upon the current therapeutic options and deliver improved, safer and more selective macrofilaricidal drugs