676 research outputs found
Recommended from our members
The implementation of problem based learning styles to teach the Coach-Athlete relationship to undergraduate Sport and Exercise Science students
This study explored problem based learning (PBL) styles and it’s suitability to improve the learning experience of level 6 (third year) Sport and Exercise Science undergraduate university students compared to a traditional style of lecturing when teaching the Coach-Athlete relationship. Sixty-four (Mage years=23.47, SD=3.44) students attended a lecture on the topic of the Coach-Athlete relationship. A PBL task was implemented using images of a coach showing a hostile approach and another image of a coach using a friendly approach. These images were used to initiate discussions about the potential problems the scenarios could elicit. At the end of the session student’s completed a questionnaire regarding their thoughts about the session’s ability to aid learning and whether they felt it was preferred over a traditional style of lecturing as well as their enjoyment of the session. Eighty one percent (n=52) of participants found the task helpful to aid learning, 66% (n=42) of participants indicated that using this style of lecture could aid learning more than a traditional approach and 73% (n=47) of participants enjoyed the task. It may be useful to use PBL styles in lecture sessions to engage students within the topic area of the Coach-Athlete relationship. PBL could also be used to help develop transferable skills for those students who want to pursue a career in coaching
Melanoma-associated antigen family protein-D4: clinical significance and functional relevance in breast cancer
Multicenter cohort study, with a nested randomized comparison, to examine the cardiovascular impact of preterm preeclampsia
This study evaluated whether planned early delivery would ameliorate cardiovascular dysfunction six months postpartum, compared to usual care with expectant management, in women with late preterm preeclampsia. We conducted a mechanistic observational study in women with preterm preeclampsia between 34+0 and 36+6 weeks’ gestation, nested within a randomised controlled trial of planned early delivery versus expectant management (usual care), in 28 maternity hospitals in England and Wales. Women were followed up six months postpartum with cardiovascular assessments. The primary outcome was a composite of systolic and/or diastolic dysfunction (by 2009 and 2016 definitions of diastolic dysfunction).
Between 27 April 2016 and 30 November 2018, 623 women were found to be eligible, of whom 420 (67%) were recruited. 133 women were randomised to planned delivery, 137 women were randomised to expectant management within the trial, while 150 women received expectant management outside of the trial. 321 (76.4%) completed their six month echocardiography assessment. 10% (31/321) had a left ventricular ejection fraction <55% whilst 71% (229/321) remained hypertensive. There were no differences in the primary outcome between the two randomised groups (planned delivery versus expectant management) using either the 2009 (RR 1.06; 95% CI 0.80, 1.40) or 2016 definitions (RR 0.78; 0.33, 1.86). In conclusion, we demonstrated that late preterm preeclampsia results in persistence of hypertension in the majority, and systolic LV dysfunction in 10%, of women six months postpartum. Planned early delivery does not affect these outcomes. Preeclampsia is not a self-limiting disease of pregnancy alone
Planned delivery to improve postpartum cardiac function in women with preterm pre-eclampsia: the PHOEBE mechanisms of action study within the PHOENIX RCT
Background Women whose pregnancies are affected by hypertensive disorders of pregnancy, in particular preterm pre-eclampsia, are at increased risk of long-term cardiovascular morbidity and mortality. Objectives To investigate the hypothesis that prolongation of a pregnancy affected by preterm pre-eclampsia managed by expectant management compared with planned early delivery would result in worse cardiovascular function 6 months postpartum. Design A randomised controlled trial. Setting 28 maternity hospitals in England and Wales. Participants Women who were eligible for the Pre-eclampsia in HOspital: Early iNductIon or eXpectant management (PHOENIX) study were approached and recruited for the PHOEBE study. The PHOENIX (Pre-eclampsia in HOspital: Early iNductIon or eXpectant management) study was a parallel-group, non-masked, multicentre, randomised controlled trial that was carried out in 46 maternity units across England and Wales. This study compared planned early delivery with expectant management (usual care) with individual randomisation in women with late preterm pre-eclampsia who were 34 weeks’ gestation to less than 37 weeks’ gestation and having a singleton or dichorionic diamniotic twin pregnancy. Interventions Postpartum follow-up included medical history, blood pressure assessment and echocardiography. All women had blood sampling performed on at least two time points from recruitment to the 6-month follow-up for assessment of cardiac necrosis markers. Main outcome measures Primary outcome was a composite of systolic and/or diastolic dysfunction (originally by 2009 guidelines then updated by 2016 guidelines, with an amended definition of diastolic dysfunction). Analyses were by intention to treat, together with a per-protocol analysis for the primary and secondary outcomes. Results Between 27 April 2016 and 30 November 2018, 623 women were found to be eligible, of whom 420 (67%) were recruited across 28 maternity units in England and Wales. A total of 133 women were allocated to planned delivery, 137 women were allocated to expectant management and a further 150 received non-randomised expectant management within usual care. The mean time from enrolment to delivery was 2.5 (standard deviation 1.9) days in the planned delivery group compared with 6.8 (standard deviation 5.3) days in the expectant management group. There were no differences in the primary outcome between women in the planned delivery group and those in the expectant management group using either the 2009 (risk ratio 1.06, 95% confidence interval 0.80 to 1.40) or the 2016 definition (risk ratio 0.78, 95% confidence interval 0.33 to 1.86). Overall, 10% (31/321) of women had a left ventricular ejection fraction < 55% and 71% of the cohort remained hypertensive at 6 months postpartum. No differences were observed between groups in cardiorespiratory outcomes prior to discharge from hospital or in systolic or diastolic blood pressure measurements. Variables associated with the primary outcome (2009 definition) at 6 months postpartum were maternal body mass index (adjusted odds ratio 1.33 per 5 kg/m2, 95% confidence interval 1.12 to 1.59 per 5 kg/m2) and maternal age (adjusted odds ratio 2.16, 95% confidence interval 1.44 to 3.22 per 10 years). Limitations include changing definitions regarding systolic and/or diastolic dysfunction. Conclusions Preterm pre-eclampsia results in persistence of hypertension in the majority of women with late preterm pre-eclampsia at 6 months postpartum and systolic dysfunction in 10%. Pre-eclampsia should not be considered a self-limiting disease of pregnancy alone. Future work Interventions aimed at reducing cardiovascular dysfunction. Trial registration Current Controlled Trials ISRCTN01879376. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 12. See the NIHR Journals Library website for further project information
“Bad Mum Guilt”: The Representation of ‘Work-Life Balance’ in UK Women’s Magazines
The social policy climate, labour market trends and gendered arrangements for paid and family work mean that ‘work-life balance’ remains a key social issue in the UK. Media representations of ‘work-life balance’ are a key source for the construction of gender and working motherhood. Despite evidence of gendered representations in media coverage of other social issues, little attention has been paid to the construction of work-life balance in UK women's magazines. Articles from the highest circulating UK women's magazines are analysed using a discursive approach to explicate constructions of work-life balance and working motherhood. The analysis reveals that multiple roles are constructed as a problematic choice leading to stress and guilt. Problems associated with multiple roles are constructed as individual problems, in a way that decontextualises and depoliticises them and normalises gendered assumptions and a gendered division of labour. Parallels can be drawn between this and wider discourses about women's daily lives and to the UK social policy context
Increased RPA1 gene dosage affects genomic stability potentially contributing to 17p13.3 duplication syndrome
A novel microduplication syndrome involving various-sized contiguous duplications in 17p13.3 has recently been described, suggesting that increased copy number of genes in 17p13.3, particularly PAFAH1B1, is associated with clinical features including facial dysmorphism, developmental delay, and autism spectrum disorder. We have previously shown that patient-derived cell lines from individuals with haploinsufficiency of RPA1, a gene within 17p13.3, exhibit an impaired ATR-dependent DNA damage response (DDR). Here, we show that cell lines from patients with duplications specifically incorporating RPA1 exhibit a different although characteristic spectrum of DDR defects including abnormal S phase distribution, attenuated DNA double strand break (DSB)-induced RAD51 chromatin retention, elevated genomic instability, and increased sensitivity to DNA damaging agents. Using controlled conditional over-expression of RPA1 in a human model cell system, we also see attenuated DSB-induced RAD51 chromatin retention. Furthermore, we find that transient over-expression of RPA1 can impact on homologous recombination (HR) pathways following DSB formation, favouring engagement in aberrant forms of recombination and repair. Our data identifies unanticipated defects in the DDR associated with duplications in 17p13.3 in humans involving modest RPA1 over-expression
Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome
A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define
Life events and treatment prognosis for depression: A systematic review and individual patient data meta-analysis
Objective: To investigate associations between major life events and prognosis independent of treatment type: (1) after adjusting for clinical prognostic factors and socio-demographics; (2) amongst patients with depressive episodes at least six-months long; and (3) patients with a first life-time depressive episode. //
Methods: Six RCTs of adults seeking treatment for depression in primary care met eligibility criteria, individual patient data (IPD) were collated from all six (n = 2858). Participants were randomized to any treatment and completed the same baseline assessment of life events, demographics and clinical prognostic factors. Two-stage random effects meta-analyses were conducted. // Results: Reporting any major life events was associated with poorer prognosis regardless of treatment type. Controlling for baseline clinical factors, socio-demographics and social support resulted in minimal residual evidence of associations between life events and treatment prognosis. However, removing factors that might mediate the relationships between life events and outcomes reporting: arguments/disputes, problem debt, violent crime, losing one's job, and three or more life events were associated with considerably worse prognoses (percentage difference in 3–4 months depressive symptoms compared to no reported life events =30.3%(95%CI: 18.4–43.3)). // Conclusions: Assessing for clinical prognostic factors, social support, and socio-demographics is likely to be more informative for prognosis than assessing self-reported recent major life events. However, clinicians might find it useful to ask about such events, and if they are still affecting the patient, consider interventions to tackle problems related to those events (e.g. employment support, mediation, or debt advice). Further investigations of the efficacy of such interventions will be important
Mutation analysis of the ATR gene in breast and ovarian cancer families
INTRODUCTION: Mutations in BRCA1, BRCA2, ATM, TP53, CHK2 and PTEN account for only 20–30% of the familial aggregation of breast cancer, which suggests the involvement of additional susceptibility genes. The ATR (ataxia-telangiectasia- and Rad3-related) kinase is essential for the maintenance of genomic integrity. It functions both in parallel and cooperatively with ATM, but whereas ATM is primarily activated by DNA double-strand breaks induced by ionizing radiation, ATR has been shown to respond to a much broader range of DNA damage. Upon activation, ATR phosphorylates several important tumor suppressors, including p53, BRCA1 and CHK1. Based on its central function in the DNA damage response, ATR is a plausible candidate gene for susceptibility to cancer. METHODS: We screened the entire coding region of the ATR gene for mutations in affected index cases from 126 Finnish families with breast and/or ovarian cancer, 75 of which were classified as high-risk and 51 as moderate-risk families, by using conformation sensitive gel electrophoresis and direct sequencing. RESULTS: A large number of novel sequence variants were identified, four of which – Glu254Gly, Ser1142Gly, IVS24-48G>A and IVS26+15C>T – were absent from the tested control individuals (n = 300). However, the segregation of these mutations with the cancer phenotype could not be confirmed, partly because of the lack of suitable DNA samples. CONCLUSION: The present study does not support a major role for ATR mutations in hereditary susceptibility to breast and ovarian cancer
A secondary analysis of the NoHoW trial
Funding Information: This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 643309. The material presented and views expressed here are the responsibility of the author(s) only. The EU Commission takes no responsibility for any use made of the information set out. Funding Information: The NoHoW Trial was funded by the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement number 643309). A detailed description of the NoHoW trial procedures can be found elsewhere ( Marques et al., 2021 ; Scott et al., 2019 ). The trial was registered with the ISRCTN registry (ISRCTN88405328). Ethical approval was granted by all local institutional ethics committees at the Universities of Lisbon (17/2016; 20-Feb-2017), Leeds (17–0082; 27-Feb-2017), and the Capital Region of Denmark (H-16030495; 8-Mar-2017). Participants were assigned to one of four intervention conditions that have access to different theory-based digitally delivered content: Publisher Copyright: © 2022 The AuthorsBackground: To date, few digital behavior change interventions for weight loss maintenance focusing on long-term physical activity promotion have used a sound intervention design grounded on a logic model underpinned by behavior change theories. The current study is a secondary analysis of the weight loss maintenance NoHoW trial and investigated putative mediators of device-measured long-term physical activity levels (six to 12 months) in the context of a digital intervention. Methods: A subsample of 766 participants (Age = 46.2 ± 11.4 years; 69.1% female; original NoHoW sample: 1627 participants) completed all questionnaires on motivational and self-regulatory variables and had all device-measured physical activity data available for zero, six and 12 months. We examined the direct and indirect effects of Virtual Care Climate on post intervention changes in moderate-to-vigorous physical activity and number of steps (six to 12 months) through changes in the theory-driven motivational and self-regulatory mechanisms of action during the intervention period (zero to six months), as conceptualized in the logic model. Results: Model 1 tested the mediation processes on Steps and presented a poor fit to the data. Model 2 tested mediation processes on moderate-to-vigorous physical activity and presented poor fit to the data. Simplified models were also tested considering the autonomous motivation and the controlled motivation variables independently. These changes yielded good results and both models presented very good fit to the data for both outcome variables. Percentage of explained variance was negligible for all models. No direct or indirect effects were found from Virtual Care Climate to long term change in outcomes. Indirect effects occurred only between the sequential paths of the theory-driven mediators. Conclusion: This was one of the first attempts to test a serial mediation model considering psychological mechanisms of change and device-measured physical activity in a 12-month longitudinal trial. The model explained a small proportion of variance in post intervention changes in physical activity. We found different pathways of influence on theory-driven motivational and self-regulatory mechanisms but limited evidence that these constructs impacted on actual behavior change. New approaches to test these relationships are needed. Challenges and several alternatives are discussed. Trial registration: ISRCTN Registry, ISRCTN88405328. Registered December 16, 2016, https://www.isrctn.com/ISRCTN88405328.publishersversionpublishe
- …