Skin microvascular vasodilatory capacity in offspring of two parents with Type 2 diabetes

Aims<br/> Microvascular dysfunction occurs in Type 2 diabetes and in subjects with fasting hyperglycaemia. It is unclear whether this dysfunction relates to dysglycaemia. This study investigated in normogylcaemic individuals whether a genetic predisposition to diabetes, or indices of insulin resistance including endothelial markers, were associated with impaired microvascular function.<br/> Methods<br/> Maximum microvascular hyperaemia to local heating of the skin was measured using laser Doppler flowmetry in 21 normoglycaemic subjects with no family history of diabetes (Group 1) and 21 normoglycaemic age, sex and body mass index-matched offspring of two parents with Type 2 diabetes (Group 2). <br/>Results<br/> Although Group 2 had normal fasting plasma glucose and glucose tolerance tests, the 120-min glucose values were significantly higher at 6.4 (5.3-6.6) mmol/l (median (25th-75th centile)) than the control group at 4.9 (4.6-5.9) mmol/l (P=0.005) and the insulinogenic index was lower at 97.1 (60.9-130.8) vs. 124.0 (97.2-177.7) (P=0.027). Skin maximum microvascular hyperaemia (Group 1: 1.56 (1.39- 1.80) vs. Group 2: 1.53 (1.30-1.98) V, P=0.99) and minimum microvascular resistance which normalizes the hyperaemia data for blood pressure (Group 1: 52.0 (43.2-67.4) vs. Group 2: 56.0 (43.7-69.6) mmHgN, P=0.70) did not differ in the two groups. Significant positive associations occurred between minimum microvascular resistance and indices of the insulin resistance syndrome; plasminogen activator inhibitor type 1 (R-s=0.46, P=0.003), t-PA (R-s=0.36, P=0.03), total cholesterol (R-s=0.35, P=0.02), and triglyceride concentration (R-s=0.35, P=0.02), and an inverse association with insulin sensitivity (R-s=-0.33, P=0.03).<br/> Conclusions<br/> In normoglycaemic adults cutaneous microvascular vasodilatory capacity is associated with features of insulin resistance syndrome, particularly with plasminogen activator inhibitor type 1. A strong family history of Type 2 diabetes alone does not result in impairment in the maximum hyperaemic response

The specialty choices of graduates from Brighton and Sussex Medical School: a longitudinal cohort study

BACKGROUND Since 2007 junior doctors in the UK have had to make major career decisions at a point when previously many had not yet chosen a specialty. This study examined when doctors in this new system make specialty choices, which factors influence choices, and whether doctors who choose a specialty they were interested in at medical school are more confident in their choice than those doctors whose interests change post-graduation. METHODS Two cohorts of students in their penultimate year at one medical school (n = 227/239) were asked which specialty interested them as a career. Two years later, 210/227 were sent a questionnaire measuring actual specialty chosen, confidence, influence of perceptions of the specialty and experiences on choice, satisfaction with medicine, personality, self-efficacy, and demographics. Medical school and post-graduation choices in the same category were deemed 'stable'. Predictors of stability, and of not having chosen a specialty, were calculated using bootstrapped logistic regression. Differences between specialties on questionnaire factors were analysed. RESULTS 50% responded (n = 105/277; 44% of the 239 Year 4 students). 65% specialty choices were 'stable'. Factors univariately associated with stability were specialty chosen, having enjoyed the specialty at medical school or since starting work, having first considered the specialty earlier. A regression found doctors who chose psychiatry were more likely to have changed choice than those who chose general practice. Confidence in the choice was not associated with stability. Those who chose general practice valued lifestyle factors. A psychiatry choice was associated with needing a job and using one's intellect to help others. The decision to choose surgical training tended to be made early. Not having applied for specialty training was associated with being lower on agreeableness and conscientiousness. CONCLUSION Medical school experiences are important in specialty choice but experiences post-graduation remain significant, particularly in some specialties (psychiatry in our sample). Career guidance is important at medical school and should be continued post-graduation, with senior clinicians supported in advising juniors. Careers advice in the first year post-graduation may be particularly important, especially for specialties which have difficulty recruiting or are poorly represented at medical school

Examining the effects of national initiatives to improve the physical health of people with psychosis in England: secondary analysis of data from the National Clinical Audit of Psychosis

Background: There are longstanding concerns regarding physical health inequalities for people with psychotic disorders. In recent years concerted efforts have been made to address these. Aims: To examine whether recent national initiatives in England have led to improvements in the physical health of people with schizophrenia and related psychoses. Methods: Secondary analysis of data from multiple rounds of a national audit of services for people with psychosis, conducted over a 9-year period. Proportions of patients in ‘good health’ according to seven discrete measures, and one composite measure derived from national standards, were compared between each round of the audit. Results: The proportion of patients in overall ‘good health’ under the care of ‘Early Intervention in Psychosis’ (EIP) teams increased between 2014 and 2019 (OR=4.65, 95% CI 3.32 to 6.52, P<0.001). There were isolated improvements for these patients in measures of ‘good health’ relating to smoking (OR=1.22, 95% CI 1.11 to 1.35, P<0.001), alcohol use (OR=1.43, 95% CI 1.23 to 1.68, P<0.001) and illicit substance use (OR=1.86, 95% CI 1.68 to 2.07, P<0.001). There was no significant change in the proportion of patients in overall ‘good health’ under the care of ‘Community Mental Health Teams’ (CMHTs) between 2011 and 2017. However, there were improvements for these patients in specific measures relating to alcohol use (OR=1.48, 95% CI 1.31 to 1.67, P=<0.001), blood glucose levels (OR=2.12, 95% CI 1.89 to 2.36, P<0.001) and blood lipids (OR=1.78, 95% CI 1.60 to 1.98, P<0.001). Conclusions: There have been modest improvements in the physical health of people with psychotic disorders over the last nine years, particularly those who are under the care of EIP teams. Continuing efforts are required if these improvements are to translate into reductions in premature mortality among people with psychosis

Alterations in Retinal Microvascular Geometry in Young Type 1 Diabetes

OBJECTIVE - To describe retinal microvascular geometric parameters in young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS - Patients with type 1 diabetes (aged 12-20 years) had clinical assessments and retinal photography following standardized protocol at a tertiary-care hospital in Sydney. Retinal microvascular geometry, including arteriolar and venular tortuosity, branching angles, optimality deviation, and length-to-diameter ratio (LDR), were measured from digitized photographs. Associations of these geometric characteristics with diabetes duration, A1C level, systolic blood pressure (SBP), and other risk factors were assessed. RESULTS - Of 1,159 patients enrolled, 944 (81.4%) had gradable photographs and 170 (14.7%) had retinopathy. Older age was associated with decreased arteriolar (P = 0.024) and venular (P = 0.002) tortuosity, and female subjects had larger arteriolar branching angle than male subjects (P = 0.03). After adjusting for age and sex, longer diabetes duration was associated with larger arteriolar branching angle (P ≤ 0.001) and increased arteriolar optimality deviation (P = 0.018), higher A1C was associated with increased arteriolar tortuosity (>8.5 vs. ≤8.5%, P = 0.008), higher SBP was associated with decreased arteriolar LDR (P = 0.002), and higher total cholesterol levels were associated with increased arteriolar LDR (P = 0.044) and decreased venular optimality deviation (P = 0.044). These associations remained after controlling for A1C, retinal vessel caliber, and retinopathy status and were seen in subjects without retinopathy. CONCLUSIONS - Key diabetes-related factors affect retinal microvascular geometry in young type 1 diabetes, even in those without evidence of retinopathy. These early retinal alterations may be markers of diabetes microvascular complications. © 2010 by the American Diabetes Association.link_to_OA_fulltex

Clinical experience in T cell deficient patients

T cell disorders have been poorly understood until recently. Lack of knowledge of underlying molecular mechanisms together with incomplete data on long term outcome have made it difficult to assess prognosis and give the most effective treatment. Rapid progress in defining molecular defects, improved supportive care and much improved results from hematopoietic stem cell transplantation (HSCT) now mean that curative treatment is possible for many patients. However, this depends on prompt recognition, accurate diagnosis and careful treatment planning

Self-Supervised Clustering on Image-Subtracted Data with Deep-Embedded Self-Organizing Map

Developing an effective automatic classifier to separate genuine sources from artifacts is essential for transient follow-ups in wide-field optical surveys. The identification of transient detections from the subtraction artifacts after the image differencing process is a key step in such classifiers, known as real-bogus classification problem. We apply a self-supervised machine learning model, the deep-embedded self-organizing map (DESOM) to this "real-bogus" classification problem. DESOM combines an autoencoder and a self-organizing map to perform clustering in order to distinguish between real and bogus detections, based on their dimensionality-reduced representations. We use 32x32 normalized detection thumbnails as the input of DESOM. We demonstrate different model training approaches, and find that our best DESOM classifier shows a missed detection rate of 6.6% with a false positive rate of 1.5%. DESOM offers a more nuanced way to fine-tune the decision boundary identifying likely real detections when used in combination with other types of classifiers, for example built on neural networks or decision trees. We also discuss other potential usages of DESOM and its limitations

Processing GOTO data with the Rubin Observatory LSST Science Pipelines I: Production of coadded frames

The past few decades have seen the burgeoning of wide field, high cadence surveys, the most formidable of which will be the Legacy Survey of Space and Time (LSST) to be conducted by the Vera C. Rubin Observatory. So new is the field of systematic time-domain survey astronomy, however, that major scientific insights will continue to be obtained using smaller, more flexible systems than the LSST. One such example is the Gravitational-wave Optical Transient Observer (GOTO), whose primary science objective is the optical follow-up of Gravitational Wave events. The amount and rate of data production by GOTO and other wide-area, high-cadence surveys presents a significant challenge to data processing pipelines which need to operate in near real-time to fully exploit the time-domain. In this study, we adapt the Rubin Observatory LSST Science Pipelines to process GOTO data, thereby exploring the feasibility of using this "off-the-shelf" pipeline to process data from other wide-area, high-cadence surveys. In this paper, we describe how we use the LSST Science Pipelines to process raw GOTO frames to ultimately produce calibrated coadded images and photometric source catalogues. After comparing the measured astrometry and photometry to those of matched sources from PanSTARRS DR1, we find that measured source positions are typically accurate to sub-pixel levels, and that measured L-band photometries are accurate to ∼50 mmag at mL∼16 and ∼200 mmag at mL∼18. These values compare favourably to those obtained using GOTO's primary, in-house pipeline, GOTOPHOTO, in spite of both pipelines having undergone further development and improvement beyond the implementations used in this study. Finally, we release a generic "obs package" that others can build-upon should they wish to use the LSST Science Pipelines to process data from other facilities

Implementation of Anaphylaxis Management Guidelines: A Register-Based Study

BACKGROUND: Anaphylaxis management guidelines recommend the use of intramuscular adrenaline in severe reactions, complemented by antihistamines and corticoids; secondary prevention includes allergen avoidance and provision of self-applicable first aid drugs. Gaps between recommendations and their implementation have been reported, but only in confined settings. Hence, we analysed nation-wide data on the management of anaphylaxis, evaluating the implementation of guidelines. METHODS: Within the anaphylaxis registry, allergy referral centres across Germany, Austria and Switzerland provided data on severe anaphylaxis cases. Based on patient records, details on reaction circumstances, diagnostic workup and treatment were collected via online questionnaire. Report of anaphylaxis through emergency physicians allowed for validation of registry data. RESULTS: 2114 severe anaphylaxis patients from 58 centres were included. 8% received adrenaline intravenously, 4% intramuscularly; 50% antihistamines, and 51% corticoids. Validation data indicated moderate underreporting of first aid drugs in the Registry. 20% received specific instructions at the time of the reaction; 81% were provided with prophylactic first aid drugs at any time. CONCLUSION: There is a distinct discrepancy between current anaphylaxis management guidelines and their implementation. To improve patient care, a revised approach for medical education and training on the management of severe anaphylaxis is warranted