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Adiposity rebound and height velocity in patients with Congenital Adrenal Hyperplasia
Get PDFObjective: Adiposity rebound is the first rise in BMI that occurs after the initial decrease during infancy. Early adiposity rebound, before age 5, is a risk factor for later obesity and metabolic problems. We investigated adiposity rebound in children with Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (CAH).Design: Longitudinal observational registry study.Methods: Height, weight and BMI from patients younger than 20 years in the I-CAH Registry was described by non-linear mixed-effects models. Covariates of glucocorticoid dose, mineralocorticoid dose, 17-Hydroxyprogesterone were assessed on growth and bone age.Results: A total of 10,261 visits within 573 patients (43.6% male) showed significant variation in age at latest peak height velocity (8.4 years (SD = 3.0) in boys; 9.0 years (SD = 1.6) in girls). Peak height velocity was more blunted in boys (7.7 cm/year (SD = 1.4)) than girls (7.4 cm/year (SD = 1.3)) in comparison to normative values. Adiposity rebound occurred earlier than age 5 years in 82% of the cohort, mean age 3.7 years (SD = 1.3) in boys and 3.9 years (SD = 0.9) in girls. Girls prescribed higher doses of glucocorticoid were associated with heavier weight in adolescence and earlier adiposity rebound. Bone age was increasingly advanced in those prescribed higher doses in both sexes.Conclusions: There is a large variation in the timing of adiposity rebound and SITAR-estimated latest peak height velocity in children with CAH. In addition to identifying individuals with CAH who may be at risk of adverse cardiometabolic outcomes these metrics may serve as early surrogate outcomes in future research investigating early-life treatment strategies.</p
Impact of surgery and complications on GI recovery after SBO:Insights from the SnapSBO cohort
Get PDFBackground: Small bowel obstruction (SBO) is a common surgical emergency associated with impaired gastrointestinal (GI) function and prolonged recovery. The PRO-diGI patient-reported outcome measure (PROM) assesses patients' reports on key domains of appetite, nausea, bowel function, well-being and overall GI function. This study evaluated the influence of demographic and treatment factors on GI recovery following SBO and examined whether these associations persisted after balancing for baseline differences using propensity score matching (PSM). Methods: An international prospective multicentre cohort study enrolled adult patients undergoing treatment for SBO of any aetiology. GI recovery was assessed using the PRO-diGI tool. Multivariable regression models were used to identify associations between clinical factors and PROM scores. Regression coefficients (β) with 95% confidence intervals were calculated. PSM was performed within the adhesional SBO subgroup to minimize confounding from differences in follow-up time and baseline characteristics. Results: Of 1734 participants, 644 completed all PROM domains. Among patients contributing PROM data, surgical intervention was associated with improved nausea (β 5.9, 95% confidence interval 1.1–11.0) and overall GI function (β 6.8, 95% confidence interval 0.54–13.0) scores. Complications were linked to worse nausea (β −9.3, 95% confidence interval −17.0 to −1.7), well-being (β −17.0, 95% confidence interval −29.0 to −4.3), and overall function (β −12.0, 95% confidence interval −22.0 to −1.4). Previous nonoperative SBO episodes were associated with reduced appetite scores (β −7.3, 95% confidence interval −13.0 to −1.7). In the adhesion PSM cohort, overall GI function remained higher after surgery, and laparoscopic adhesiolysis was associated with superior appetite and overall function scores. Discussion: Surgical treatment without complications was associated with improved patient-reported GI recovery after SBO. Persistence of these associations following matching indicates that patient-reported GI recovery differs across treatment pathways in selected patients, supporting the feasibility and discriminatory value of PRO-diGI as a patient-centred outcome measure.</p
Hormone Replacement Therapy for Menopausal Symptoms and the Risk of Cardiometabolic Disease:Current Evidence and Future Directions
Get PDFBackground: The transition through menopause is accompanied by a series of adverse metabolic changes which are associated with an increased risk of cardiometabolic disease, a major cause of mortality in women after midlife. Whilst the indication for menopausal hormone replacement therapy (HRT) is the control of menopausal symptoms, understanding and discussing the cardiometabolic impacts of HRT are necessary to facilitate informed decision-making at treatment initiation and continuation, and to select appropriate regimens. Methodology: A narrative review. Results: Existing evidence suggests that HRT is likely to impact the development of metabolic risk factors including visceral fat accumulation, adverse changes in lipid profile, blood pressure and glycaemic control. Findings from randomised controlled trials have refined our understanding of the impact of HRT on cardiometabolic outcomes including coronary heart disease and stroke. Furthermore, recent research has highlighted the impact of the menopause on the development and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) that has been poorly studied in the context of HRT. The route of oestrogen administration, timing of initiation and type of progestogen are all likely to affect the impact of HRT on many of these outcomes. There has recently been extensive media interest in HRT in some countries resulting in increased prescription rates. Understanding the impact of HRT on cardiometabolic risk is therefore particularly important. In this narrative review, we discuss the existing evidence and clinical guidelines on the effect of HRT on cardiometabolic risk factors and the risk of coronary heart disease, stroke and MASLD, highlighting areas of uncertainty and priorities for further research.</p
When does blockchain create value premium in organic food supply chains? Game-theoretic modeling and experimental evidence
Get PDFPurpose – This study aims to investigate the conditions and key factors influencing the adoption of blockchain technology in the organic food supply chain, where adoption remains limited despite the technology's potential benefits. Design/methodology/approach – Drawing upon the Technology Acceptance Model, this study develops a mixed-methods approach combining game-theoretic modeling and scenario-based experiments to analyze the enablers of blockchain adoption from the perspectives of technology investment cost, survival rate of fresh products, accuracy of information disclosed by blockchain, and consumer perceived freshness uncertainty. Findings – Equilibrium results from the game-theoretic model indicate that technology investment cost is the most critical factor affecting firms' blockchain adoption decisions. When investment cost is low, firms are likely to adopt blockchain regardless of other factors. When investment cost is high, adoption only occurs if either (1) the improvement in product survival rate is substantial, or (2) the improvement is moderate, but both perceived freshness uncertainty and information accuracy exceed certain thresholds. Scenario-based experiments confirm the negative impact of investment cost on adoption willingness, and the moderating effects of perceived freshness uncertainty and information accuracy. Originality/value – This study advances the literature by combining analytical modeling with empirical experimentation to uncover the strategic considerations that shape blockchain adoption in organic food supply chains. These findings help to clarify the decision rules for organic food firms and further enrich the understanding of why and when to introduce blockchain in the supply chain.</p
Differences in endoscopy characteristics between providers with the highest and lowest Post Endoscopy Upper Gastrointestinal Cancer rates in England
No full textBackgroundPost-endoscopy upper gastrointestinal cancer (PEUGIC) rates vary over threefold between endoscopy providers in England. To determine if variations in endoscopy characteristics contribute, providers with the lowest and highest PEUGIC rates were compared. MethodsEndoscopy providers were categorised into quartiles based on PEUGIC rates and those in the highest and lowest quartiles studied. Data for diagnostic upper gastrointestinal (UGI) endoscopies performed between January 2019 and February 2020 extracted from the National Endoscopy Database. Multivariable regression analysis explored the endoscopy characteristics associated with the lowest PEUGIC rate providers, after adjusting for patient characteristics and indications. ResultsIn total, 328,354 diagnostic UGI endoscopies performed by 54 providers were included. Endoscopy characteristics positively associated with the lowest PEUGIC rate providers included: training sessions (Odds Ratio 1.85 (95% CI 1.81-1.90)); intravenous sedation use (1.09 (1.07-1.11)); endoscopist average UGI endoscopy annual volume 101-200 (1.05 (1.02-1.07) and 201-300 (1.16 (1.13-1.19)). Endoscopy characteristics inversely associated with the lowest PEUGIC rate providers included: endoscopy half-day sessions with average ≥9 points (0.72 (0.71-0.74)); endoscopists not on nursing, specialty or trainee register (0.83 (0.81-0.85)); and biopsies during endoscopy (0.84 (0.83-0.86)). Compliance with national quality standards to biopsy high risk conditions was better by providers with lowest PEUGIC rates. DiscussionTraining sessions, more endoscopists with minimum annual endoscopy volumes >100, more intravenous sedation, less biopsies and more lower intensity endoscopy sessions were associated with the lowest PEUGIC rate providers. These findings may help guide efforts to reduce PEUGIC and improve endoscopy quality in future.<br/
Challenging Evolutionary Paradigms:<i>Daphnia </i>Populations Resurrected From Unpolluted Environments Show Enhanced Detoxification Ability to Aromatic Pollutants
Get PDFUnderstanding how organisms respond to chemical stress requires disentangling genetically encoded (constitutive) adaptations from environmentally induced (plastic) responses. This challenge is particularly acute for polycyclic aromatic hydrocarbons (PAHs), widespread aquatic pollutants with well‐documented toxicity, where mechanisms of tolerance, including host–microbiome interactions, are unexplored. We used Daphnia magna, a keystone freshwater species with clonal reproduction and dormant egg banks to test population‐specific (constitutive) responses to phenanthrene (PHE), a common PAH. Populations resurrected from contrasting historical environments were exposed to sub‐lethal PHE concentrations, and both host transcriptomes and gut microbiomes were profiled to assess induced responses. Transcriptomic analysis revealed distinct, population‐specific responses in detoxification, stress signalling, and endocrine regulation. Unexpectedly, the semi‐pristine (pollution‐naïve) population showed higher tolerance, with robust induction of cytochrome P450 and hormonal pathways, while populations historically exposed to pollution exhibited chronic stress signatures and reduced plasticity. Gut microbiome profiling revealed PHE‐induced functional shifts across populations, with the pollution‐naïve population showing broader stress‐associated responses and historically exposed populations to pollutants exhibiting more detoxification‐focused microbiome profiles. Both host and microbial datasets consistently showed enrichment in pyruvate and carbon metabolism, indicating coordinated energy mobilisation and detoxification responses. Our results show that historical exposure to chemical stress and wider pollution does not necessarily confer enhanced physiological tolerance to PHE. Instead, hydrocarbon stress elicits coordinated, functionally linked responses across the host and its associated microbiome. By leveraging Daphnia's unique ecology and evolutionary history, we disentangle constitutive from plastic responses and show that microbiome functional reconfiguration under PHE exposure is coordinated with host responses, contributing to population‐specific profiles
Healthcare professionals’ views on barriers, facilitators and optimisation of care for perinatal anxiety:a qualitative investigation
Get PDFBackground: The experience of pregnancy and having a baby is a time of significant change and transition. One in five perinatal women experience problems with their emotional wellbeing and mental health in this period; adjustment, anxiety and depressive illnesses being most common. Whilst investment in specialist perinatal mental health pathways continues, there is limited understanding of healthcare professionals’ views and experiences of these pathways and of support available for women with mild or moderate mental health problems. This study explored healthcare professionals’ views on the barriers and facilitators to identification and management of perinatal anxiety, and on how to optimise care pathways. Methods: In-depth semi-structured interviews were conducted with a purposive sample of healthcare professionals in universal perinatal services (including maternity, primary care, and health-visiting) and specialist (including talking therapies, maternal and perinatal) mental health services. Data were analysed using framework analysis. Results: Interviews were conducted with 62 healthcare professionals from England and Scotland. 40% of the sample stated they had received no training in perinatal mental health, and 45% reported that they did not use standardised or validated questions or scales when enquiring about mental health. Themes related to barriers, facilitators, and service optimisation are presented for each stage of their care pathway: identification; disclosure; referral and assessment; care and treatment. Recommendations for optimising care included improving mental health education and training to strengthen perinatal healthcare and developing a sustainable perinatal mental health pathway, including for women with mild mental health problems. Conclusions: Healthcare professionals considered that the healthcare pathway for women with severe mental health problems was clear and well-developed, but that healthcare for women with mild and moderate anxiety and mental health problems was under-developed. Improvements in perinatal mental health education, in mandatory training for healthcare professionals, should be put in place in order to improve care. Increasing the number of staff and time available to address perinatal mental health is vital but requires additional resources and should be part of long-term strategies for funding
Incipient decomposition of nitrogen-expanded Austenite in Si-containing high-Ni alloys during nitriding
Get PDFIn contrast to the nitride formation in steels nitrided at 480–600°C, low-temperature nitriding (LTN) generates a precipitate-free, interstitially-supersaturated nitrogen-expanded Austenite (γN) case in Austenitic stainless steels (SSs). However, the temperature/time-dependent Cr-nitride precipitation in γN triggers long-range Cr migration, severely deteriorating corrosion resistance. Hence, the upper LTN temperature is often limited to 450°C. Consequently, the diffusion-based γN-304/316 cases formed are relatively thin, with poor load-bearing capacity (typically < 15 µm, 500 HV0.3), and require extended treatment times (e.g. 20–50 hrs). Here, we demonstrate the concomitant formation of ultra-fine Cr/N-rich (1–6 nm) and Si/N-rich (3–30 nm) nanostructures, with short-range Cr segregation, during the early-stage decomposition of the N-modified Austenite cases from a range of Si-containing and high-Ni SSs nitrided at 430 and 480°C. Depending on temperature and Ni/Si concentration, two early γN decomposition stages are defined based on the Austenitic matrix, i.e. a N-supersaturated γN (Stage I) and a ‘less-expanded’ γ(N) (Stage II). The Cr/N-rich nanophase initiates via Cr-N nanoclustering along one of the {200} planes. The Cr-containing, Si/N-rich nanostructure is postulated to evolve from rock-salt FCC-structured (Cr1-xSix)N to a nanocomposite consisting of amorphous Si3N4 in-between CrN nanocrystallites. The partially decomposed γN/γ(N) case obtained at 480°C/10 hrs presents high case thickness (reaching 26 µm), high hardness (at 1550–1750 HV0.025), and enhanced load-bearing capacity (up to 1244 HV0.3), while still providing good corrosion resistance. This points to the development of ‘Nitralloy-like’ Austenitic steels and a time-efficient nitriding approach for partially decomposed nitrogen-expanded Austenite cases.</p
Expansion of normal subsets of odd-order elements in finite groups
No full textLet G be a finite group and K a normal subset consisting of odd-order elements. The rational closure of K, denoted DK, is the set of elements x ∈ G with the property that ⟨x⟩ = ⟨y⟩ for some y in K. If K2 ⊆ DK, we prove that ⟨K⟩ is soluble
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