853 research outputs found

    The effects of UV radiation and electron bombardment on the flashover characteristics of alumina based high voltage insulators in vacuum

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    The effects of UV and electron bombardment on the flashover characteristics of highly stressed alumina insulators in vacuum were investigated as part of a project to improve the performance of high voltage insulators in large particle accelerators at CERN. An experimental system has been developed which allowed photon and electron bombardment of stressed insulator samples under vacuum, in order to investigate the causes and characteristics of insulator flashover, and to identify sample preparations which could improve insulator performance

    Improving quality of care and outcome at very preterm birth: the Preterm Birth research programme, including the Cord pilot RCT

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    BACKGROUND: Being born very premature (i.e. before 32 weeks’ gestation) has an impact on survival and quality of life. Improving care at birth may improve outcomes and parents’ experiences. OBJECTIVES: To improve the quality of care and outcomes following very preterm birth. DESIGN: We used mixed methods, including a James Lind Alliance prioritisation, a systematic review, a framework synthesis, a comparative review, qualitative studies, development of a questionnaire tool and a medical device (a neonatal resuscitation trolley), a survey of practice, a randomised trial and a protocol for a prospective meta-analysis using individual participant data. SETTING: For the prioritisation, this included people affected by preterm birth and health-care practitioners in the UK relevant to preterm birth. The qualitative work on preterm birth and the development of the questionnaire involved parents of infants born at three maternity hospitals in southern England. The medical device was developed at Liverpool Women’s Hospital. The survey of practice involved UK neonatal units. The randomised trial was conducted at eight UK tertiary maternity hospitals. PARTICIPANTS: For prioritisation, 26 organisations and 386 individuals; for the interviews and questionnaire tool, 32 mothers and seven fathers who had a baby born before 32 weeks’ gestation for interviews evaluating the trolley, 30 people who had experienced it being used at the birth of their baby (19 mothers, 10 partners and 1 grandmother) and 20 clinicians who were present when it was being used; for the trial, 261 women expected to have a live birth before 32 weeks’ gestation, and their 276 babies. INTERVENTIONS: Providing neonatal care at very preterm birth beside the mother, and with the umbilical cord intact; timing of cord clamping at very preterm birth. MAIN OUTCOMES MEASURES: Research priorities for preterm birth; feasibility and acceptability of the trolley; feasibility of a randomised trial, death and intraventricular haemorrhage. REVIEW METHODS: Systematic review of Cochrane reviews (umbrella review); framework synthesis of ethics aspects of consent, with conceptual framework to inform selection criteria for empirical and analytical studies. The comparative review included studies using a questionnaire to assess satisfaction with care during childbirth, and provided psychometric information. RESULTS: Our prioritisation identified 104 research topics for preterm birth, with the top 30 ranked. An ethnographic analysis of decision-making during this process suggested ways that it might be improved. Qualitative interviews with parents about their experiences of very preterm birth identified two differences with term births: the importance of the staff appearing calm and of staff taking control. Following a comparative review, this led to the development of a questionnaire to assess parents’ views of care during very preterm birth. A systematic overview summarised evidence for delivery room neonatal care and revealed significant evidence gaps. The framework synthesis explored ethics issues in consent for trials involving sick or preterm infants, concluding that no existing process is ideal and identifying three important gaps. This led to the development of a two-stage consent pathway (oral assent followed by written consent), subsequently evaluated in our randomised trial. Our survey of practice for care at the time of birth showed variation in approaches to cord clamping, and that no hospitals were providing neonatal care with the cord intact. We showed that neonatal care could be provided beside the mother using either the mobile neonatal resuscitation trolley we developed or existing equipment. Qualitative interviews suggested that neonatal care beside the mother is valued by parents and acceptable to clinicians. Our pilot randomised trial compared cord clamping after 2 minutes and initial neonatal care, if needed, with the cord intact, with clamping within 20 seconds and initial neonatal care after clamping. This study demonstrated feasibility of a large UK randomised trial. Of 135 infants allocated to cord clamping ≥ 2 minutes, 7 (5.2%) died and, of 135 allocated to cord clamping ≤ 20 seconds, 15 (11.1%) died (risk difference –5.9%, 95% confidence interval –12.4% to 0.6%). Of live births, 43 out of 134 (32%) allocated to cord clamping ≥ 2 minutes had intraventricular haemorrhage compared with 47 out of 132 (36%) allocated to cord clamping ≤ 20 seconds (risk difference –3.5%, 95% CI –14.9% to 7.8%). LIMITATIONS: Small sample for the qualitative interviews about preterm birth, single-centre evaluation of neonatal care beside the mother, and a pilot trial. CONCLUSIONS: Our programme of research has improved understanding of parent experiences of very preterm birth, and informed clinical guidelines and the research agenda. Our two-stage consent pathway is recommended for intrapartum clinical research trials. Our pilot trial will contribute to the individual participant data meta-analysis, results of which will guide design of future trials. FUTURE WORK: Research in preterm birth should take account of the top priorities. Further evaluation of neonatal care beside the mother is merited, and future trial of alternative policies for management of cord clamping should take account of the meta-analysis. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003038 and CRD42013004405. In addition, Current Controlled Trials ISRCTN21456601. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 7, No. 8. See the NIHR Journals Library website for further project information

    Strong negative self regulation of Prokaryotic transcription factors increases the intrinsic noise of protein expression

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    Background Many prokaryotic transcription factors repress their own transcription. It is often asserted that such regulation enables a cell to homeostatically maintain protein abundance. We explore the role of negative self regulation of transcription in regulating the variability of protein abundance using a variety of stochastic modeling techniques. Results We undertake a novel analysis of a classic model for negative self regulation. We demonstrate that, with standard approximations, protein variance relative to its mean should be independent of repressor strength in a physiological range. Consequently, in that range, the coefficient of variation would increase with repressor strength. However, stochastic computer simulations demonstrate that there is a greater increase in noise associated with strong repressors than predicted by theory. The discrepancies between the mathematical analysis and computer simulations arise because with strong repressors the approximation that leads to Michaelis-Menten-like hyperbolic repression terms ceases to be valid. Because we observe that strong negative feedback increases variability and so is unlikely to be a mechanism for noise control, we suggest instead that negative feedback is evolutionarily favoured because it allows the cell to minimize mRNA usage. To test this, we used in silico evolution to demonstrate that while negative feedback can achieve only a modest improvement in protein noise reduction compared with the unregulated system, it can achieve good improvement in protein response times and very substantial improvement in reducing mRNA levels. Conclusions Strong negative self regulation of transcription may not always be a mechanism for homeostatic control of protein abundance, but instead might be evolutionarily favoured as a mechanism to limit the use of mRNA. The use of hyperbolic terms derived from quasi-steady-state approximation should also be avoided in the analysis of stochastic models with strong repressors

    Questioning policy, youth participation and lifestyle sports

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    Young people have been identified as a key target group for whom participation in sport and physical activity could have important benefits to health and wellbeing and consequently have been the focus of several government policies to increase participation in the UK. Lifestyle sports represent one such strategy for encouraging and sustaining new engagements in sport and physical activity in youth groups, however, there is at present a lack of understanding of the use of these activities within policy contexts. This paper presents findings from a government initiative which sought to increase participation in sport for young people through provision of facilities for mountain biking in a forest in south-east England. Findings from qualitative research with 40 young people who participated in mountain biking at the case study location highlight the importance of non-traditional sports as a means to experience the natural environments through forms of consumption which are healthy, active and appeal to their identities. In addition, however, the paper raises questions over the accessibility of schemes for some individuals and social groups, and the ability to incorporate sports which are inherently participant-led into state-managed schemes. Lifestyle sports such as mountain biking involve distinct forms of participation which present a challenge for policy-makers who seek to create and maintain sustainable communities of youth participants

    Sexual Arousal Patterns of Identical Twins with Discordant Sexual Orientations

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    Genetically identical twins can differ in their self-reported sexual orientations. However, whether the twins’ subjective reports reflect valid differences in their sexual orientations is unknown. Measures of sexual orientation, which are free of the limitations of self-report, include genital arousal and pupil dilation while viewing sexual stimuli depicting men or women. We examined these responses in 6 male twin pairs and 9 female twin pairs who reported discordant sexual orientations. Across measures, heterosexual male twins responded more strongly to women than to men. Their homosexual co-twins showed an opposite pattern. Heterosexual female twins responded equally to both sexes, whereas their homosexual co-twins responded somewhat more to women than men. These differences within pairs were similar to differences between unrelated heterosexual and homosexual males and females. Our study provides physiological evidence confirming twins’ discordant sexual orientations, thereby supporting the importance of the non-shared environment for the development of sexual orientation and sexual arousal
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