Why are women still leaving academic medicine? A qualitative study within a London Medical School

Objectives: To identify factors that influenced women who chose to leave academic medicine. Design and main outcome measures: Independent consultants led a focus group of women in medicine who had left academia after completion of their postgraduate research degree at Imperial College London Faculty of Medicine. Thematic analysis was performed on the transcribed conversations. Participants and setting: Nine women physicians who completed a postgraduate degree (MD or PhD) at a large London Medical School and Academic Health Sciences Centre, Imperial College London, but did not go on to pursue a career in academic medicine. Results: Influences to leave clinical academia were summarised under eight themes—career intentions, supervisor support, institutional human resources support, inclusivity, work–life balance, expectations, mentors and role models, and pregnancy and maternity leave. Conclusion: The women in our focus group reported several factors contributing to their decision to leave clinical academia, which included lack of mentoring tailored to specific needs, low levels of acceptance for flexible working to help meet parental responsibilities and perceived explicit gender biases. We summarise the multiple targeted strategies that Imperial College London has implemented to promote retention of women in academic medicine, although more research needs to be done to ascertain the most effective interventions

Asp295 Stabilizes the Active-Site Loop Structure of Pyruvate Dehydrogenase, Facilitating Phosphorylation of Ser292 by Pyruvate Dehydrogenase-Kinase

We have developed an in vitro system for detailed analysis of reversible phosphorylation of the plant mitochondrial pyruvate dehydrogenase complex, comprising recombinant Arabidopsis thalianaα2β2-heterotetrameric pyruvate dehydrogenase (E1) plus A. thaliana E1-kinase (AtPDK). Upon addition of MgATP, Ser292, which is located within the active-site loop structure of E1α, is phosphorylated. In addition to Ser292, Asp295 and Gly297 are highly conserved in the E1α active-site loop sequences. Mutation of Asp295 to Ala, Asn, or Leu greatly reduced phosphorylation of Ser292, while mutation of Gly297 had relatively little effect. Quantitative two-hybrid analysis was used to show that mutation of Asp295 did not substantially affect binding of AtPDK to E1α. When using pyruvate as a variable substrate, the Asp295 mutant proteins had modest changes in kcat, Km, and kcat/Km values. Therefore, we propose that Asp295 plays an important role in stabilizing the active-site loop structure, facilitating transfer of the γ-phosphate from ATP to the Ser residue at regulatory site one of E1α

Does combined osteopenia/osteoporosis and sarcopenia confer greater risk of falls and fracture than either condition alone in older men? The Concord Health and Ageing in Men Project

Background It is unclear whether older men with osteopenia/osteoporosis and sarcopenia (so-called osteosarcopenia) are at greater risk of falls and fractures than those with either condition alone. Methods One thousand five hundred seventy-five community-dwelling men aged ≥70 years had appendicular lean mass, total hip and lumbar spine bone mineral density determined by dual-energy x-ray absorptiometry, and completed hand grip strength and gait speed tests. Osteopenia/osteoporosis was defined as a T-score at any site ≤−1.0 SD. Sarcopenia was defined using the European Working Group on Sarcopenia algorithm. Participants were contacted every 4 months for 6 ± 2 years to ascertain incident fractures (confirmed by radiographic reports) and for 2 years for incident falls. Results Prevalence of osteosarcopenia was 8%, while 34% of participants had osteopenia/osteoporosis alone and 7% had sarcopenia alone. Men with osteosarcopenia had significantly increased fall (incidence rate ratio: 1.41; 95% confidence interval [CI]: 1.02 to 1.95) and fracture risk (hazard ratio: 1.87; 95% CI: 1.07 to 3.26) compared with men with neither osteopenia/osteoporosis nor sarcopenia. There was no statistical interaction between osteopenia/osteoporosis and sarcopenia, and falls and fracture risk were not different for osteosarcopenia compared with either condition alone (all p > .05). Conclusions Community-dwelling older men with combined osteopenia/osteoporosis and sarcopenia do not have increased falls and fracture risk compared with those with either condition. Further research is required to clarify whether the term “osteosarcopenia” has any meaning above and beyond either term alone and therefore potential clinical utility for falls and fracture prediction.NHMRC (project grant number 301916) and the Ageing and Alzheimer’s Institute. D.Scott is supported by a NHRMC Career Development Fellowship (GNT1123014

Prevalence and correlates of cardiometabolic multimorbidity among hypertensive individuals: A cross-sectional study in rural South Asia—Bangladesh, Pakistan and Sri Lanka

Objective: To determinate the prevalence and correlates of cardiometabolic multimorbidity (CMM), and their cross-country variation among individuals with hypertension residing in rural communities in South Asia.Design: A cross-sectional study.Setting: Rural communities in Bangladesh, Pakistan and Sri Lanka.Participants: A total of 2288 individuals with hypertension aged ≥40 years from the ongoing Control of Blood Pressure and Risk Attenuation- Bangladesh, Pakistan and Sri Lanka clinical trial.Main outcome measures: CMM was defined as the presence of ≥2 of the conditions: diabetes, chronic kidney disease, heart disease and stroke. Logistic regression was done to evaluate the correlates of CMM.Results: About 25.4% (95% CI 23.6% to 27.2%) of the hypertensive individuals had CMM. Factors positively associated with CMM included residing in Bangladesh (OR 3.42, 95% CI 2.52 to 4.65) or Sri Lankan (3.73, 95% CI 2.48 to 5.61) versus in Pakistan, advancing age (2.33, 95% CI 1.59 to 3.40 for 70 years and over vs 40-49 years), higher waist circumference (2.15, 95% CI 1.42 to 3.25) for Q2-Q3 and 2.14, 95% CI 1.50 to 3.06 for Q3 and above), statin use (2.43, 95% CI 1.84 to 3.22), and higher levels of triglyceride (1.01, 95% CI 1.01 to 1.02 per 5 mg/dL increase). A lower odds of CMM was associated with being physically active (0.75, 95% CI 0.57 to 0.97). A weak inverted J-shaped association between International Wealth Index and CMM was found (p for non-linear=0.058), suggesting higher risk in the middle than higher or lower socioeconomic strata.Conclusions: CMM is highly prevalent in rural South Asians affecting one in four individuals with hypertension. There is an urgent need for strategies to concomitantly manage hypertension, cardiometabolic comorbid conditions and associated determinants in South Asia

The psychosocial and clinical outcomes following orbital decompression surgery for thyroid eye disease and predictors of change in quality of life

Objective: Thyroid eye disease (TED) has been found to reduce quality of life for many patients due to changes in their appearance and vision, although some appear to adjust better than others. This study was designed to investigate whether a patient’s quality of life changes after having orbital decompression for improvement of appearance, vision, or both, and whether any demographic, clinical or psychosocial factors can predict which patients might benefit from this surgery. Design: This study employed a within-subjects repeated measures design, where patients were assessed before, and at 6 weeks and 6 months after surgery. Subjects: One hundred and twenty-three adults (>18 years) with TED and undergoing orbital decompression surgery were recruited at Moorfields Eye Hospital. Methods: Participants received lateral wall, medial wall, 2.5 or 3 wall decompression, and were followed up after surgery with a range of psychosocial and clinical assessments. Main Outcome Measures: The Graves’ Ophthalmopathy Quality of Life (GO-QOL) scale was completed at each time point and this was used as the dependent variable in each hierarchical multiple regression model. Results: Significant improvements were found in all clinical characteristics following orbital decompression and in most psychosocial variables. GO-QOL visual function scores did not change significantly until 6 months after surgery. In contrast, GO-QOL appearance scores changed significantly by 6 weeks after surgery and continued to increase to 6 months, reaching a minimal clinically important difference for this scale. None of the changes in clinical or psychosocial outcomes significantly predicted change in GO-QOL visual function. However, the hierarchical regression model explained 79% of the variance in change in GO-QOL appearance, with change in subjective evaluation of appearance being the only unique predictor of change in appearance-related quality of life. Conclusions: This study highlights the importance of appearance-related cognitions in predicting quality of life outcomes after surgery. Implications for clinical practice need to be considered in light of the limitations of this study, but it is suggested that psychosocial interventions targeting appearance-related cognitive processes - in particular personal evaluation of appearance - could enhance the quality of life outcomes for patients with TED undergoing orbital decompression surgery

Synthesis of some 6,6' -methylene- and 6,6' -sulphone-biscoumarins

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