Prevalence of Large‐for‐Gestational Age and Macrosomia Among Livebirths in 23 Low‐ and Middle‐Income Countries Between 2000 and 2021: An Individual Participant Data Analysis

ABSTRACT Objective To examine the prevalence of large‐for‐gestational age (LGA) and macrosomia in 23 countries between 2000 and 2021. Design Descriptive multi‐country secondary data analysis. Setting Subnational, population‐based cohort studies ( k  = 45 for LGA, k  = 25 for macrosomia) in 23 low‐ and middle‐income countries (LMICs). Population Liveborn infants. Methods We conducted a secondary analysis of individual‐level data from the Vulnerable Newborn Measurement Collaboration, using INTERGROWTH‐21st standards to define LGA (> 90th centile for gestational age and sex) and macrosomia (≥ 4000 g, regardless of gestational age). We included LMIC population‐based datasets with reliable gestational age and birthweight data, excluding studies with small sample sizes, high missing data, or implausible measurements. Prevalence estimates were stratified by region, study period and gestational age, and results were summarised as medians and interquartile ranges (IQR). Main Outcome Measures Prevalence of LGA and macrosomia. Results Among 476 939 live births, the median prevalence of LGA was 5.1% (IQR: 2.9%–9.6%) and was highest in Latin America and the Caribbean at 9.6% (4 studies, IQR: 2.7%–16.1%) and lowest in South Asia at 2.7% (13 studies, IQR: 2.3%–3.7%). Over time, the median LGA prevalence increased from 4.9% (12 studies; IQR: 4.1%–7.9%) during the period from 2000 to 2010 to 5.9% (33 studies, IQR: 2.7%–11.2%) from 2011 to 2021. Term LGA was more common at 3.2% (0.9–5.1) than preterm or post‐term LGA. Among 313 064 live births, the median prevalence of macrosomia was 1.3% ( n  = 313 064, IQR: 0.2%–2.4%), which was highest in Latin America and the Caribbean (4 studies, 3.1%, IQR: 0.7%–6.8%) and lowest in South Asia (8 studies, 0.1%, IQR: 0.0%–0.7%). The median prevalence remained stable over time: 1.1% (8 studies, IQR: 0.2%–3.1%) in older studies (2000–2010) and 1.3% (17 studies, IQR: 0.5%–2.4%) in more recent studies (2011–2021). Term macrosomia was more common at 1.2% (0.2–2.0) than preterm and post‐term macrosomia. Conclusions The overall prevalence of LGA and macrosomia was lower in these LMIC studies than is reported in high‐income countries. The prevalence of large babies was highest in Latin America and the Caribbean.

Benthic Observation Survey System ( BOSS ) for surveys of marine benthic habitats

Abstract Most platforms for collecting images to characterise marine benthic habitats involve a downward or forward‐facing field of view that is relatively constrained (~70°), covering a relatively small area of benthos (downward ~1 m 2 , forward ~25 m 2 ). Here we propose the use of a four‐camera platform having a wide combined field of view (~280°), covering a much greater area (up to 100 m 2 ). We also present a stereo‐camera configuration that has the added benefit of being able to accurately measure sample area and dimensions of benthic biota. The design proposed is robust and self‐righting, facilitating rapid deployment and retrieval from a range of vessels, depths and environments. We present an exemplar workflow to generate a habitat map (~100 km 2 ) within a no‐take National Park Zone within the South‐west Corner Marine Park, Australia and demonstrate the benefit of increasing the field of view to estimate habitat heterogeneity. The relatively broad sample unit of this wide‐field drop camera is well suited to estimating coverage (e.g. of a seagrass bed) and habitat mapping. It is time‐efficient in the field, enabling spatially balanced sampling designs to acquire ground‐truthing data for medium‐ to large‐scale habitat mapping projects. This platform is a practical tool to monitor change in marine environments and assess the environmental impact (e.g. sea bed alteration) of activities such as offshore energy or fishing gears.

Wellcounter: Automated high‐throughput phenotyping for aquatic microinvertebrates

Abstract Using phenotypic information extracted from digital images through automated computer vision analysis has become a promising avenue in ecological and evolutionary research. However, acquiring large quantities of high‐quality image data and processing them efficiently often remain a bottleneck. Here, we introduce the Wellcounter, an advanced platform designed for the automated high‐throughput phenotyping of aquatic microinvertebrates (100–2000 μm), utilizing common multiwell plates to facilitate large‐scale ecological experiments. The system automates image acquisition, processing and analysis, enabling the tracking of hundreds of populations with minimal daily manual effort. Key hardware components include a high‐resolution digital camera, a telecentric lens and a motorized XY linear guide system based on an open‐source design that moves to each individual well. A dark‐field illumination ring, which travels synchronously with the camera and lens, provides constant and standardized light conditions and enhances the visualization of microinvertebrates within each well, improving detection accuracy. Our prototype can handle 84 six‐well plates in two batches, ensuring efficient imaging and analysis of over 500 populations. The software, developed in Python, supports detailed population size measurements, growth rate analysis and swimming behaviour quantification. It includes modules for image acquisition control, image analysis and motion analysis, ensuring comprehensive data collection and interpretation. We also provide a module for generating ‘ground truth’ datasets, allowing to label the positions of all detectable specimens in an image, and an optimization module to fine‐tune imaging parameters for a new study organism. Validation of the Wellcounter was conducted using rotifers. The platform demonstrated high accuracy in detecting and counting individuals, as well as in measuring population growth rates and swimming behaviour. Image analysis parameters were optimized to minimize false negatives and false positives. We discuss adapting this protocol for different microorganisms and hardware configurations, as well as general caveats and current limitations of this phenotyping approach. For those interested in developing image analysis algorithms, we provide large annotated datasets, including high‐resolution movies and images with known quantities and positions of specimens. The approach and resources provided in this study aim to facilitate the adoption and further development of automated image analysis technologies in ecological research.

Immunotherapeutic targeting of aging‐associated isoDGR motif in chronic lung inflammation

Abstract Accumulation of damaged biomolecules in body tissues is the primary cause of aging and age‐related chronic diseases. Since this damage often occurs spontaneously, it has traditionally been regarded as untreatable, with typical therapeutic strategies targeting genes or enzymes being ineffective in this domain. In this report, we demonstrate that an antibody targeting the isoDGR damage motif in lung tissue can guide immune clearance of harmful damaged proteins in vivo, effectively reducing age‐linked lung inflammation. We observed age‐dependent accumulation of the isoDGR motif in human lung tissues, as well as an 8‐fold increase in isoDGR‐damaged proteins in lung fibrotic tissues compared with healthy tissue. This increase was accompanied by marked infiltration of CD68+/CD11b + macrophages, consistent with a role for isoDGR in promoting chronic inflammation. We therefore assessed isoDGR function in mice that were either naturally aged or lacked the isoDGR repair enzyme. IsoDGR‐protein accumulation in mouse lung tissue was strongly correlated with chronic inflammation, pulmonary edema, and hypoxemia. This accumulation also induced mitochondrial and ribosomal dysfunction, in addition to features of cellular senescence, thereby contributing to progressive lung damage over time. Importantly, treatment with anti‐isoDGR antibody was able to reduce these molecular features of disease and significantly reduced lung pathology in vivo.

3 D Mitochondrial Structure in Aging Human Skeletal Muscle: Insights Into MFN ‐2‐Mediated Changes

ABSTRACT Age‐related skeletal muscle atrophy, known as sarcopenia, is characterized by loss of muscle mass, strength, endurance, and oxidative capacity. Although exercise has been shown to mitigate sarcopenia, the underlying governing mechanisms are poorly understood. Mitochondrial dysfunction is implicated in aging and sarcopenia; however, few studies explore how mitochondrial structure contributes to this dysfunction. In this study, we sought to understand how aging impacts mitochondrial three‐dimensional (3D) structure and its regulators in skeletal muscle. We hypothesized that aging leads to remodeling of mitochondrial 3D architecture permissive to dysfunction and is ameliorated by exercise. Using serial block‐face scanning electron microscopy (SBF‐SEM) and Amira software, mitochondrial 3D reconstructions from patient biopsies were generated and analyzed. Across five human cohorts, we correlate differences in magnetic resonance imaging, mitochondria 3D structure, exercise parameters, and plasma immune markers between young (under 50 years) and old (over 50 years) individuals. We found that mitochondria are less spherical and more complex, indicating age‐related declines in contact site capacity. Additionally, aged samples showed a larger volume phenotype in both female and male humans, indicating potential mitochondrial swelling. Concomitantly, muscle area, exercise capacity, and mitochondrial dynamic proteins showed age‐related losses. Exercise stimulation restored mitofusin 2 (MFN2), one such of these mitochondrial dynamic proteins, which we show is required for the integrity of mitochondrial structure. Furthermore, we show that this pathway is evolutionarily conserved, as Marf, the MFN2 ortholog in Drosophila , knockdown alters mitochondrial morphology and leads to the downregulation of genes regulating mitochondrial processes. Our results define age‐related structural changes in mitochondria and further suggest that exercise may mitigate age‐related structural decline through modulation of mitofusin 2.

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Cover legend: The cover image is based on the article 3D Mitochondrial Structure in Aging Human Skeletal Muscle: Insights Into MFN‐2‐Mediated Changes by Estevão Scudese et al., https://doi.org/10.1111/acel.70054

Harmonization of alcohol use data and mortality across a multi‐national HIV cohort collaboration

Abstract Background Alcohol use is measured in diverse ways across settings. Harmonization of measures is necessary to assess effects of alcohol use in multi‐cohort collaborations, such as studies of people with HIV (PWH). Methods Data were combined from 14 HIV cohort studies (nine European, five North American) participating in the Antiretroviral Therapy Cohort Collaboration. We analyzed data on adult PWH with measured alcohol use at any time from 6 months before starting antiretroviral therapy. Five cohorts measured alcohol use with AUDIT‐C and others used cohort‐specific measures. We harmonized alcohol use as grams/day, calculated using country‐level definitions of a standard drink. For Alcohol Use Disorders Identification Test (AUDIT‐C), we used Items 1 (frequency) and 2 (number of drinks on a typical day). Where alcohol was measured in categories, we used the mid‐point to calculate grams/day. We used multivariable Cox models to estimate associations of alcohol use with mortality. Results Alcohol use data were available for 83,424 PWH, 22,447 (27%) had AUDIT‐C measures and 60,977 (73%) recorded the number of drinks/units per week/day. Of the sample, 19,150 (23%) were female, 54,006 (65%) had White ethnicity, and median age was 42 years. Median alcohol use was 0.3 g/day (interquartile range [IQR] 0–4.8) and 0 g/day (IQR 0–20) for those with and without AUDIT‐C. There was a J‐shaped relationship between grams/day and mortality, with higher mortality for PWH reporting no alcohol use (adjusted hazard ratio [aHR] 1.46; 95% CI: 1.23–1.72) and heavier (>61.0 g/day) alcohol use (aHR 1.92; 1.41–2.59) compared with 0.1–5.5 g/day among those with AUDIT‐C measures. Associations were similar among those with non‐AUDIT‐C measures. Conclusions Grams/day is a useful metric to harmonize diverse measures of alcohol use. Magnitudes of associations of alcohol use with mortality may differ by setting and measurement method. Higher mortality among those with heavier alcohol use strengthens the case for interventions to reduce drinking.

Disentangling the Contributions to Phenotypic Change in Conservation Breeding: A Case Study in a Breeding Program of an Endangered Migratory Songbird

ABSTRACT Conservation breeding programs play a crucial role in managing endangered wildlife, yet successful reintroduction remains challenging due to the low fitness of released individuals and complexities in conservation breeding. This study addresses these ongoing challenges by investigating morphological changes in the endangered Eastern loggerhead shrike ( Lanius ludovicianus migrans ) breeding program across multiple facilities in southern Canada and the United States, which was started in 1997. Using mixed‐effect animal models and estimated breeding values, we explore potential signals of evolutionary change in the program and assess variables contributing to morphological variation and change. Our findings reveal dynamic variation in shrike morphology across years and generations, with some evidence of evolutionary change in shrike mass. However, mass changes appear to be unrelated to selection in captivity. Additionally, recent gene flow from the wild correlates with mass and tarsus width, suggesting gene flow from the wild might drive some of the morphological change. This study provides insights into the evolutionary processes in shaping morphological traits in a conservation breeding program. The identified genetic drivers offer considerations for refining breeding practices and insights into evolutionary change in a conservation breeding program, presenting significant implications for wildlife managers and conservation practitioners. Importantly, observed temporal heterogeneities and trends are likely influenced not only by genetic changes but also by plasticity, and plasticity could mask simultaneously occurring genetic change. More research is needed to characterize and determine how and if plastic responses are directionally shaping phenotypic distributions in captivity.

Discovery of a regulatory polymorphism in the bovine PICALM gene associated with milk α S1 ‐casein concentration

Primary care management of stroke in people with dementia: Linked registry and general practice data

Abstract Objectives To evaluate whether risk factor management in Australian general practices for secondary prevention of stroke differs by dementia status. Methods A retrospective study of adults with acute stroke or transient ischaemic attack (TIA) from 2014 to 2018, using de‐identified linked data (2014–2020) from the Australian Stroke Clinical Registry and three Primary Health Networks in Victoria. Eligibility included being discharged home or to inpatient rehabilitation, and having two or more encounters with general practice during the chronic phase (7–18 months) postindex stroke/TIA. We evaluated the assessment of cardiometabolic risk factors (blood pressure, serum lipids, blood glucose and urinary protein), prescription of prevention medications and attainment of risk factor targets, within 7–18 months postindex stroke/TIA. Regression models were used to determine any differences in risk factor management. Results Among 3376 eligible survivors of stroke/TIA (median age 73.9 years, 22% TIA), 140 (4%) had evidence of a dementia diagnosis. In multivariable analyses, dementia was associated with fewer risk factors being assessed (incidence rate ratio [IRR] .86, 95% confidence interval [95% CI] CI .76–.98) or medication classes being prescribed (IRR .88, 95% CI .78–.98). No significant difference was observed in the attainment of risk factor targets. Conclusions Although patients with dementia were less often assessed for risk factors or prescribed medications for secondary prevention of stroke, the control of risk factors did not differ by dementia status. Current findings may reflect appropriate clinical decision‐making for managing people with dementia approaching the end of life.