A realist evaluation of a physical activity participation intervention for children and youth with disabilities: What works, for whom, in what circumstances, and how?

Background: The need to identify strategies that facilitate involvement in physical activity for children and youth with disabilities is recognised as an urgent priority. This study aimed to describe the association between context, mechanisms and outcome(s) of a participation-focused physical activity intervention to understand what works, in what conditions, and how. Methods: This study was designed as a realist evaluation. Participant recruitment occurred through purposive and theoretical sampling of children and parents participating in the Local Environment Model intervention at Beitostolen Healthsports Centre in Norway. Ethnographic methods comprising participant observation, interviews, and focus groups were employed over 15 weeks in the field. Data analysis was completed using the context-mechanism-outcome framework of realist evaluation. Context-mechanism-outcome connections were generated empirically from the data to create a model to indicate how the program activated mechanisms within the program context, to enable participation in physical activity. Results: Thirty one children with a range of disabilities (mean age 12y 6 m (SD 2y 2 m); 18 males) and their parents (n=44; 26 mothers and 18 fathers) participated in the study. Following data synthesis, a refined program theory comprising four context themes, five mechanisms, and six outcomes, were identified. The mechanisms (choice, fun, friends, specialised health professionals, and time) were activated in a context that was safe, social, learning-based and family-centred, to elicit outcomes across all levels of the International Classification of Functioning, Disability and Health. Conclusions: The interaction of mechanisms and context as a whole facilitated meaningful outcomes for children and youth with disabilities, and their parents. Whilst optimising participation in physical activity is a primary outcome of the Local Environment Model, the refined program theory suggests the participation-focused approach may act as a catalyst to promote a range of outcomes. Findings from this study may inform future interventions attempting to enable participation in physical activity for children and youth with disabilities

Pollen, biomarker and stable isotope evidence of late Quaternary environmental change at Lake McKenzie, southeast Queensland

Unravelling links between climate change and vegetation response during the Quaternary is important if the climate–environment interactions of modern systems are to be fully understood. Using a sediment core from Lake McKenzie, Fraser Island, we reconstruct changes in the lake ecosystem and surrounding vegetation over the last ca. 36.9 cal kyr. Evidence is drawn from multiple sources, including pollen, micro-charcoal, biomarker and stable isotope (C and N) analyses, and is used to gain a better understanding of the nature and timing of past ecological changes that have occurred at the site. The glacial period of the record, from ca. 36.9 to 18.3 cal kyr BP, is characterised by an increased abundance of plants of the aquatic and littoral zone, indicating lower lake water levels. High abundance of biomarkers and microfossils of the colonial green alga Botryococcus occurred at this time and included large variation in individual botryococcene d13C values. A slowing or ceasing of sediment accumulation occurred during the time period from ca. 18.3 to 14.0 cal kyr BP. By around 14.0 cal kyr BP fire activity in the area was reduced, as was abundance of littoral plants and terrestrial herbs, suggesting wetter conditions from that time. The Lake McKenzie pollen record conforms to existing records from Fraser Island by containing evidence of a period of reduced effective precipitation that commenced in the mid-Holocene

Gene Expression Signature in Peripheral Blood Detects Thoracic Aortic Aneurysm

BACKGROUND: Thoracic aortic aneurysm (TAA) is usually asymptomatic and associated with high mortality. Adverse clinical outcome of TAA is preventable by elective surgical repair; however, identifying at-risk individuals is difficult. We hypothesized that gene expression patterns in peripheral blood cells may correlate with TAA disease status. Our goal was to identify a distinct gene expression signature in peripheral blood that may identify individuals at risk for TAA. METHODS AND FINDINGS: Whole genome gene expression profiles from 94 peripheral blood samples (collected from 58 individuals with TAA and 36 controls) were analyzed. Significance Analysis of Microarray (SAM) identified potential signature genes characterizing TAA vs. normal, ascending vs. descending TAA, and sporadic vs. familial TAA. Using a training set containing 36 TAA patients and 25 controls, a 41-gene classification model was constructed for detecting TAA status and an overall accuracy of 78+/-6% was achieved. Testing this classifier on an independent validation set containing 22 TAA samples and 11 controls yielded an overall classification accuracy of 78%. These 41 classifier genes were further validated by TaqMan real-time PCR assays. Classification based on the TaqMan data replicated the microarray results and achieved 80% classification accuracy on the testing set. CONCLUSIONS: This study identified informative gene expression signatures in peripheral blood cells that can characterize TAA status and subtypes of TAA. Moreover, a 41-gene classifier based on expression signature can identify TAA patients with high accuracy. The transcriptional programs in peripheral blood leading to the identification of these markers also provide insights into the mechanism of development of aortic aneurysms and highlight potential targets for therapeutic intervention. The classifier genes identified in this study, and validated by TaqMan real-time PCR, define a set of promising potential diagnostic markers, setting the stage for a blood-based gene expression test to facilitate early detection of TAA

The ubiquitin proteasome system in neuropathology

The ubiquitin proteasome system (UPS) orchestrates the turnover of innumerable cellular proteins. In the process of ubiquitination the small protein ubiquitin is attached to a target protein by a peptide bond. The ubiquitinated target protein is subsequently shuttled to a protease complex known as the 26S proteasome and subjected to degradative proteolysis. The UPS facilitates the turnover of proteins in several settings. It targets oxidized, mutant or misfolded proteins for general proteolytic destruction, and allows for the tightly controlled and specific destruction of proteins involved in development and differentiation, cell cycle progression, circadian rhythms, apoptosis, and other biological processes. In neuropathology, alteration of the UPS, or mutations in UPS target proteins may result in signaling abnormalities leading to the initiation or progression of tumors such as astrocytomas, hemangioblastomas, craniopharyngiomas, pituitary adenomas, and medulloblastomas. Dysregulation of the UPS may also contribute to tumor progression by perturbation of DNA replication and mitotic control mechanisms, leading to genomic instability. In neurodegenerative diseases caused by the expression of mutant proteins, the cellular accumulation of these proteins may overload the UPS, indirectly contributing to the disease process, e.g., sporadic Parkinsonism and prion diseases. In other cases, mutation of UPS components may directly cause pathological accumulation of proteins, e.g., autosomal recessive Parkinsonism and spinocerebellar ataxias. Defects or dysfunction of the UPS may also underlie cognitive disorders such as Angelman syndrome, Rett syndrome and autism, and muscle and nerve diseases, e.g., inclusion body myopathy and giant axon neuropathy. This paper describes the basic biochemical mechanisms comprising the UPS and reviews both its theoretical and proven involvement in neuropathological diseases. The potential for the UPS as a target of pharmacological therapy is also discussed

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI 2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining https://researchonline.ljmu.ac.uk/images/research_banner_face_lab_290.jpgunderweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity

Environmental controls on branched tetraether lipid distributions in tropical East African lake sediments

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