Children and young people's body mass index measures derived from routine data sources: A national data linkage study in Wales.

BACKGROUND: Routine monitoring of Body Mass Index (BMI) in general practice, and via national surveillance programmes, is essential for the identification, prevention, and management of unhealthy childhood weight. We examined and compared the presence and representativeness of children and young people's (CYPs) BMI recorded in two routinely collected administrative datasets: general practice electronic health records (GP-BMI) and the Child Measurement Programme for Wales (CMP-BMI), which measures height and weight in 4-5-year-old school children. We also assessed the feasibility of combining GP-BMI and CMP-BMI data for longitudinal analyses. METHODS: We accessed de-identified population-level GP-BMI data for calendar years 2011 to 2019 for 246,817 CYP, and CMP-BMI measures for 222,772 CYP, held within the Secure Anonymised Information Linkage Databank. We examined the proportion of CYP in Wales with at least one GP-BMI record, its distribution by child socio-demographic characteristics, and trends over time. We compared GP-BMI and CMP-BMI distributions. We quantified the proportion of children with a CMP-BMI measure and a follow-up GP-BMI recorded at an older age and explored the representativeness of these measures. RESULTS: We identified a GP-BMI record in 246,817 (41%) CYP, present in a higher proportion of females (54.2%), infants (20.7%) and adolescents. There was no difference in the deprivation profile of those with a GP-BMI measurement. 31,521 CYP with a CMP-BMI had at least one follow-up GP-BMI; those with a CMP-BMI considered underweight or very overweight were 87% and 70% more likely to have at least one follow-up GP-BMI record respectively compared to those with a healthy weight, as were males and CYP living in the most deprived areas of Wales. CONCLUSIONS: Records of childhood weight status extracted from general practice are not representative of the population and are biased with respect to weight status. Linkage of information from the national programme to GP records has the potential to enhance discussions around healthy weight at the point of care but does not provide a representative estimate of population level weight trajectories, essential to provide insights into factors determining a healthy weight gain across the early life course. A second CMP measurement is required in Wales

Weight-loss Independent Clinical and Metabolic Biomarkers Associated with Type 2 Diabetes Remission Post-bariatric/metabolic Surgery

PURPOSE: Remission of type 2 diabetes (T2D) can be achieved by many, but not all, people following bariatric/metabolic surgery. The mechanisms underlying T2D remission remain incompletely understood. This observational study aimed to identify novel weight-loss independent clinical, metabolic and genetic factors that associate with T2D remission using comprehensive phenotyping. MATERIALS AND METHODS: Ten patients without T2D remission (non-remitters) were matched to 10 patients with T2D remission (remitters) for age, sex, type of surgery, body weight, BMI, post-operative weight loss, duration from surgery and duration of T2D. Detailed body composition assessed using magnetic resonance imaging, gut hormones, serum metabolomics, insulin sensitivity, and genetic risk scores for T2D and anthropometric traits were assessed. RESULTS: Remitters had significantly greater β-cell function and circulating acyl ghrelin levels, but lower visceral adipose tissue (VAT): subcutaneous adipose tissue (SAT) ratio than non-remitters. Branched-chain amino acids (BCAAs) and VLDL particle size were the most discriminant metabolites between groups. A significant positive correlation between, VAT area, VAT:SAT ratio and circulating levels of BCAAs was observed, whereas a significant negative correlation between BCAAs and β-cell function was revealed. CONCLUSION: We highlight a potentially novel relationship between VAT and BCAAs, which may play a role in glucoregulatory control. Improvement in β-cell function, and the role ghrelin plays in its recovery, is likely another key factor influencing T2D remission post-surgery. These findings suggest that adjunctive approaches that target VAT loss and restoration of BCAA metabolism might achieve higher rates of long-term T2D remission post-surgery

The Privatization of Metropolitan Jakarta's (Jabodetabek) Urban Fringes:The Early Stages of "Post-Suburbanization" in Indonesia

Problem, research strategy, and findings: Recent metropolitan development in developed countries is associated with post-suburbia, or a decline in population in the former central city and the growth of polycentric structures outside the traditional core. Current urban development in Asian cities, particularly in the Jakarta metropolitan region (Jabodetabek), also reflects an early stage of post-suburbia. We examine physical development patterns and the changing role of public and private sectors, although our approach is descriptive in nature. The rapid growth in fringe areas that have developed from dormitory communities into independent towns, triggered by privatization of industrial estates and multifunction new towns, shows typical post-suburban patterns. The national government's pro-growth economic policies and the local autonomy granted to local governments have given the private sector the power to largely control the acquisition, development, and management of land in fringe areas, accelerating post-suburban development patterns.Takeaway for practice: Planners in developing nations must be alert to the rapidly increasing role of the private sector, recognizing how the private sector can help the government to respond to regional needs for housing, jobs, shopping and educational opportunities, and infrastructure while understanding the key role that planning can and should play in ensuring private sector actions do not exacerbate regional problems and lead to uncoordinated public responses

Water Governance in Decentralising Indonesia

Under new democratic regimes in the country of the South, governance innovation is often found at the regional level. This article, using the concept of institutional capacity, shows that powerful efforts affecting regional water resource coordination emerge locally. The paper analyzes fresh water cooperation in the urban region of Cirebon, Indonesia. It is shown that city and their surrounding regions in decentralizing Indonesia show signs of increasing institutional capacity between local actors. An informal approach and discretionary local decision-making, influenced by logic of appropriateness and tolerance are influential. At the same time, these capacities are compromised by significant inequality and a unilateral control of water resources, and they are being challenged by a strong authoritarian political culture inherited from a history of centralized government. The paper points to the need to establish greater opportunities for water governance at the regional level to transcend inter-local rivalry, and thus improve decentralized institutional capacity further

A systematic review of published physiologically-based kinetic models and an assessment of their chemical space coverage

Across multiple sectors, including food, cosmetics and pharmaceutical industries, there is a need to predict the potential effects of xenobiotics. These effects are determined by the intrinsic ability of the substance, or its derivatives, to interact with the biological system, and its concentration-time profile at the target site. Physiologically-based kinetic (PBK) models can predict organ-level concentration-time profiles, however, the models are time and resource intensive to generate de novo. Read-across is an approach used to reduce or replace animal testing, wherein information from a data-rich chemical is used to make predictions for a data-poor chemical. The recent increase in published PBK models presents the opportunity to use a read-across approach for PBK modelling, i.e. to use PBK model information from one chemical to inform the development or evaluation of a PBK model for a similar chemical. Essential to this process, is identifying for which chemicals a PBK model already exists. Herein, the results of a systematic review of existing PBK models, compliant with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) format, are presented. Model information including species, sex, life-stage, route of administration, software platform used and availability of model equations was captured for 7,541 PBK models. Chemical information (identifiers and physico-chemical properties) has also been recorded for 1,150 unique chemicals associated with these models. This PBK model dataset has been made readily accessible, as a Microsoft Excel spreadsheet, providing a valuable resource, for those developing, using or evaluating PBK models in industry, academia and the regulatory sectors

Molecular Fingerprint-Derived Similarity Measures for Toxicological Read-Across: Recommendations for Optimal Use

Computational approaches are increasingly used to predict toxicity, in part due to pressures to find alternatives to animal testing. Read-across is the “new paradigm” which aims to predict toxicity by identifying similar, data rich, source compounds. This assumes that similar molecules tend to exhibit similar activities, i.e. molecular similarity is integral to read-across. Various molecular fingerprints and similarity measures may be used to calculate molecular similarity. This study investigated the value and concordance of the Tanimoto similarity values calculated using six widely used fingerprints within six toxicological datasets. There was considerable variability in the similarity values calculated from the various molecular fingerprints for diverse compounds, although they were reasonably concordant for homologous series acting via a common mechanism. The results suggest generic fingerprint-derived similarities are likely to be optimally predictive for local datasets, i.e. following sub-categorisation. Thus, for read-across, generic fingerprint-derived similarities are likely to be most predictive after chemicals are placed into categories (or groups), then similarity is calculated within those categories, rather than for a whole chemically diverse dataset

Molecular Fingerprint-Derived Similarity Measures for Toxicological Read-Across: Recommendations for Optimal Use

Computational approaches are increasingly used to predict toxicity, in part due to pressures to find alternatives to animal testing. Read-across is the “new paradigm” which aims to predict toxicity by identifying similar, data rich, source compounds. This assumes that similar molecules tend to exhibit similar activities, i.e. molecular similarity is integral to read-across. Various molecular fingerprints and similarity measures may be used to calculate molecular similarity. This study investigated the value and concordance of the Tanimoto similarity values calculated using six widely used fingerprints within six toxicological datasets. There was considerable variability in the similarity values calculated from the various molecular fingerprints for diverse compounds, although they were reasonably concordant for homologous series acting via a common mechanism. The results suggest generic fingerprint-derived similarities are likely to be optimally predictive for local datasets, i.e. following sub-categorisation. Thus, for read-across, generic fingerprint-derived similarities are likely to be most predictive after chemicals are placed into categories (or groups), then similarity is calculated within those categories, rather than for a whole chemically diverse dataset