Is arterial stiffening associated with adiposity, severity of obesity and other contemporary cardiometabolic markers in a community sample of adolescents with obesity in the UK?

BACKGROUND: Cardiovascular disease (CVD) prediction is problematic within groups of obese adolescents as measures such as adiposity and metabolic markers lack validation. Pulse wave velocity (PWV), a proxy for arterial stiffening, is a potential way to contemporaneously capture adolescents at greater risk of CVD. OBJECTIVES: To investigate associations between PWV and 1) adiposity and 2) other conventional metabolic factors in a community sample of (>95th centile body mass index (BMI)). Design and setting: Cross-sectional measurement and analysis in a hospital-based research centre drawn from a community sample of adolescents recruited to an obesity intervention at baseline. PATIENTS: 174 adolescents (12-19 years) with obesity (>95th centile BMI). 37% were male, while 66 (38%) were white, 53 (30%) black, 36 (21%) South Asian, 19 (11%) mixed/other. Participants with endocrine, genetic causes of obesity and chronic medical conditions (excluding asthma) were excluded. MEASURES: BMI z-score (zBMI), waist z-score, fat mass index (FMI: measured using bioimpedance), sagittal abdominal dimension (SAD), cardiometabolic blood tests and resting blood pressure (BP) were collected. Carotid-radial PWV was measured by a single operator. RESULTS: PWV was associated with age but not pubertal stage. PWV was positively associated with adiposity (zBMI: coefficient 0.44 (95% CI 0.08 to 0.79); FMI: coefficient 0.05 (95% CI 0.00 to 0.10); waist z-score: coefficient 0.27 (95% CI 0.00 to 0.53); SAD: coefficient 0.06 (95% CI: 0.00 to 0.12)). There was no association between PWV and BP, and few associations with cardiometabolic bloods. Associations between PWV and adiposity measures were robust to adjustment in multivariable models except for SAD. Participants with zBMI >2.5 SD and >3.5 SD had greater average PWV but overlap between groups was large. CONCLUSIONS: In our sample, increasing adiposity was positively associated with arterial stiffness, however partitioning by severity was not reliable. Lack of associations between BP, cardiometabolic bloods and arterial stiffness questions the reliability of these factors for predicting CVD risk in adolescents with obesity

Analysis of lifetime mortality trajectories in wildlife disease research: BaSTA and Beyond

This is the final version. Available from MDPI via the DOI in this record. Wildlife hosts are important reservoirs of a wide range of human and livestock infections worldwide, and in some instances, wildlife populations are threatened by disease. Yet wildlife diseases are difficult to monitor, and we often lack an understanding of basic epidemiological parameters that might inform disease management and the design of targeted interventions. The impacts of disease on host survival are generally associated with age, yet traditional epidemiological models tend to use simplistic categories of host age. Mortality trajectory analysis provides the opportunity to understand age-specific impacts of disease and uncover epidemiological patterns across complete life histories. Here, we use Bayesian survival trajectory analysis (BaSTA) software to analyse capture-mark-recapture data from a population of wild badgers Meles meles naturally infected with Mycobacterium bovis, the causative agent of tuberculosis in badgers and cattle. We reveal non-constant mortality trajectories, and show that infection exaggerates an age-dependent increase in late-life mortality. This study provides evidence for actuarial senescence in badgers, a species previously believed to display constant mortality throughout life. Our case study demonstrates the application of mortality trajectory analysis in wildlife disease research, but also highlights important limitations. We recommend BaSTA for mortality trajectory analysis in epidemiological research, but also suggest combining approaches that can include diagnostic uncertainty and the movement of hosts between disease states as they age. We recommend future combinations of multi-state and multi-event modelling frameworks for complex systems incorporating age-varying disease states.NERCthe Animal and Plant Health AgencyUniversity of ExeterDepartment for Environment, Food and Rural Affair

High genetic diversity at the extreme range edge: nucleotide variation at nuclear loci in Scots pine (Pinus sylvestris L.) in Scotland

Nucleotide polymorphism at 12 nuclear loci was studied in Scots pine populations across an environmental gradient in Scotland, to evaluate the impacts of demographic history and selection on genetic diversity. At eight loci, diversity patterns were compared between Scottish and continental European populations. At these loci, a similar level of diversity (θsil=~0.01) was found in Scottish vs mainland European populations, contrary to expectations for recent colonization, however, less rapid decay of linkage disequilibrium was observed in the former (ρ=0.0086±0.0009, ρ=0.0245±0.0022, respectively). Scottish populations also showed a deficit of rare nucleotide variants (multi-locus Tajima's D=0.316 vs D=−0.379) and differed significantly from mainland populations in allelic frequency and/or haplotype structure at several loci. Within Scotland, western populations showed slightly reduced nucleotide diversity (πtot=0.0068) compared with those from the south and east (0.0079 and 0.0083, respectively) and about three times higher recombination to diversity ratio (ρ/θ=0.71 vs 0.15 and 0.18, respectively). By comparison with results from coalescent simulations, the observed allelic frequency spectrum in the western populations was compatible with a relatively recent bottleneck (0.00175 × 4Ne generations) that reduced the population to about 2% of the present size. However, heterogeneity in the allelic frequency distribution among geographical regions in Scotland suggests that subsequent admixture of populations with different demographic histories may also have played a role

Importance sampling and Bayesian model comparison in ecology and evolution

This is the final version. Available on open access from Wiley via the DOI in this record. Data availability statement: All code and data presented in this manuscript are available via Zenodo (Hudson, 2023).Bayesian approaches to the modelling of ecological systems are increasingly popular, but there are competing methods for formal model comparisons. Here, we focus on the task of performing multimodel inference through estimating posterior model weights, which encompasses uncertainties in the choice of competing model structure into the inference outputs. Model-based approaches such as reversible-jump Markov chain Monte Carlo (RJ-MCMC) are flexible and allow multimodel inference, but can be complex to implement and optimise, and so we translate a model-based approach for ecological applications using Importance Sampling to estimate the marginal likelihood of the data given a particular model. This approach allows for model comparison through the estimation of Bayes' Factors or interpretable posterior model probabilities, yielding model weights that facilitate multimodel inference through Bayesian model averaging. We demonstrate Importance Sampling with two case study investigations in animal demography: censused analysis of banded mongoose (Mungos mungo) survival where missing data are uncommon, and capture–mark–recapture analysis of European badger (Meles meles) survival where data are commonly missing. We compare outcomes of the model comparison using the Importance Sampling approach to those obtained through single-model inference approaches using Deviance information criteria and the Watanabe–Akaike information criteria. The results of the Importance Sampling method aligns with RJ-MCMC model comparisons while often being more straightforward to fit and optimise, particularly if the competing models are non-nested.Natural Environment Research Council (NERC)Animal and Plant Health AgencyUniversity of Exete

Molecular Phylogenetics of the Genus Neoconocephalus (Orthoptera, Tettigoniidae) and the Evolution of Temperate Life Histories

BACKGROUND:The katydid genus Neoconocephalus (25+ species) has a prominent acoustic communication system and occurs in large parts of the Neotropics and Nearctic. This group has been subject of numerous behavioral, physiological, and evolutionary studies of its acoustic communication system. Two distinct life histories occur in this group: The tropical life history incorporates multiple generations/year and direct egg development without environmental triggers. Temperate life history is characterized by overwintering in the egg stage, cold trigger of egg development, and one generation/year. This study reconstructs the phylogenetic relationships within the genus to (1) determine the evolutionary history of the temperate life history, and (2) to support comparative studies of evolutionary and physiological problems in this genus. METHODOLOGY/PRINCIPAL FINDINGS:We used Amplified Fragment Length Polymorphisms (AFLP), and sequences of two nuclear loci and one mitochondrial locus to reconstruct phylogenetic relationships. The analysis included 17 ingroup and two outgroup species. AFLP and mitochondrial data provided resolution at the species level while the two nuclear loci revealed only deeper nodes. The data sets were combined in a super-matrix to estimate a total evidence tree. Seven of the temperate species form a monophyletic group; however, three more temperate species were placed as siblings of tropical species. CONCLUSIONS/SIGNIFICANCE:Our analyses support the reliability of the current taxonomic treatment of the Neoconocephalus fauna of Caribbean, Central, and North America. Ancestral state reconstruction of life history traits was not conclusive, however at least four transitions between life histories occurred among our sample of species. The proposed phylogeny will strengthen conclusions from comparative work in this group

Recent Advances in Electrosynthesized Molecularly Imprinted Polymer Sensing Platforms for Bioanalyte Detection

The accurate detection of biological materials has remained at the forefront of scientific research for decades. This includes the detection of molecules, proteins, and bacteria. Biomimetic sensors look to replicate the sensitive and selective mechanisms that are found in biological systems and incorporate these properties into functional sensing platforms. Molecularly imprinted polymers (MIPs) are synthetic receptors that can form high affinity binding sites complementary to the specific analyte of interest. They utilise the shape, size, and functionality to produce sensitive and selective recognition of target analytes. One route of synthesizing MIPs is through electropolymerization, utilising predominantly constant potential methods or cyclic voltammetry. This methodology allows for the formation of a polymer directly onto the surface of a transducer. The thickness, morphology, and topography of the films can be manipulated specifically for each template. Recently, numerous reviews have been published in the production and sensing applications of MIPs; however, there are few reports on the use of electrosynthesized MIPs (eMIPs). The number of publications and citations utilising eMIPs is increasing each year, with a review produced on the topic in 2012. This review will primarily focus on advancements from 2012 in the use of eMIPs in sensing platforms for the detection of biologically relevant materials, including the development of increased polymer layer dimensions for whole bacteria detection and the use of mixed monomer compositions to increase selectivity toward analytes

Statistical validation of the criteria for symptom remission in schizophrenia: Preliminary findings

<p>Abstract</p> <p>Background</p> <p>Published methods for assessing remission in schizophrenia are variable and none have been definitively validated or standardized. Andreasen et al (2005) suggest systematic operational criteria using eight PANSS items for which patients must score ≤ 3 (mild) for at least six months.</p> <p>Methods</p> <p>Using data from a one year, multi-site clinical trial (n = 675) remission criteria were compared to total PANSS scores and other endpoints and demonstrate excellent agreement with overall clinical status.</p> <p>Results</p> <p>Compared to total PANSS score of 60 points and other criteria, at time points > 6 months (8 and 12 months) the specificity of the remission criteria was 85%, i.e. of the patients who had a total score >60, 85% were classified as "not in remission." Sensitivity was also very high; 75% of patients with scores of <60 were classified as "in remission."Patients who dropped out of the trial were more likely not to be in remission prior to dropping out.</p> <p>Conclusion</p> <p>These findings indicate that the remission criteria are both sensitive and specific indicators of clinical status. Additional analyses are required to determine if remission status predicts other outcomes, such as employment, independent living, and prognosis.</p

Systematic population screening, using biomarkers and genetic testing, identifies 2.5% of the U.K. pediatric diabetes population with monogenic diabetes

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.OBJECTIVE: Monogenic diabetes is rare but is an important diagnosis in pediatric diabetes clinics. These patients are often not identified as this relies on the recognition of key clinical features by an alert clinician. Biomarkers (islet autoantibodies and C-peptide) can assist in the exclusion of patients with type 1 diabetes and allow systematic testing that does not rely on clinical recognition. Our study aimed to establish the prevalence of monogenic diabetes in U.K. pediatric clinics using a systematic approach of biomarker screening and targeted genetic testing. RESEARCH DESIGN AND METHODS: We studied 808 patients (79.5% of the eligible population) <20 years of age with diabetes who were attending six pediatric clinics in South West England and Tayside, Scotland. Endogenous insulin production was measured using the urinary C-peptide creatinine ratio (UCPCR). C-peptide-positive patients (UCPCR ≥0.2 nmol/mmol) underwent islet autoantibody (GAD and IA2) testing, with patients who were autoantibody negative undergoing genetic testing for all 29 identified causes of monogenic diabetes. RESULTS: A total of 2.5% of patients (20 of 808 patients) (95% CI 1.6-3.9%) had monogenic diabetes (8 GCK, 5 HNF1A, 4 HNF4A, 1 HNF1B, 1 ABCC8, 1 INSR). The majority (17 of 20 patients) were managed without insulin treatment. A similar proportion of the population had type 2 diabetes (3.3%, 27 of 808 patients). CONCLUSIONS: This large systematic study confirms a prevalence of 2.5% of patients with monogenic diabetes who were <20 years of age in six U.K. clinics. This figure suggests that ∼50% of the estimated 875 U.K. pediatric patients with monogenic diabetes have still not received a genetic diagnosis. This biomarker screening pathway is a practical approach that can be used to identify pediatric patients who are most appropriate for genetic testing.This work presents independent research commissioned by the Health Innovation Challenge Fund, a parallel funding partnership between the Wellcome Trust and the Department of Health (grant HICF-1009-041); and was supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility and the South West Peninsula Diabetes Research Network. M.S. is supported by the NIHR Exeter Clinical Research Facility. T.J.M. is funded by an NIHR CSO Fellowship. S.E. and A.T.H. are both Wellcome Trust Senior Investigators. E.R.P. is a Wellcome Trust New Investigator. A.T.H. is an NIHR Senior Investigator

Boundaries of Semantic Distraction: Dominance and Lexicality Act at Retrieval

Three experiments investigated memory for semantic information with the goal of determining boundary conditions for the manifestation of semantic auditory distraction. Irrelevant speech disrupted the free recall of semantic category-exemplars to an equal degree regardless of whether the speech coincided with presentation or test phases of the task (Experiment 1) and occurred regardless of whether it comprised random words or coherent sentences (Experiment 2). The effects of background speech were greater when the irrelevant speech was semantically related to the to-be-remembered material, but only when the irrelevant words were high in output dominance (Experiment 3). The implications of these findings in relation to the processing of task material and the processing of background speech is discussed