Publications by authors named "Manning A"

Introduction Pediatric to adult health care transition (HCT) is critical to maintaining the health and wellness of patients, and pediatric and adult providers often do not feel prepared to shepherd patients through this process. Methods  We designed an HCT curriculum consisting of nine podcasts paired with existing ambulatory experiential learning opportunities for internal medicine-pediatric residents (n=6). Before and after the curriculum we evaluated resident HCT self-assessment and resident performance working with a standardized patient (SP) and standardized parent in a novel objective structured clinical examination (OSCE) station designed to assess HCT skills.

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  • The All of Us Research Program (AoU) aims to collect a diverse dataset from over one million people in the USA to enhance research on human diseases, focusing on genetic and phenotypic information.
  • This study developed and validated algorithms to identify cases of type 1 and type 2 diabetes using electronic health records and survey data, striving for improved accuracy in case-control studies.
  • The results showed the EHR-only algorithm had a better association with type 1 diabetes genetic scores, while the EHR+ algorithm was superior for type 2 diabetes, identifying significantly more cases than previous definitions and providing new validated definitions for both diabetes types.
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Functional neurological disorder (FND) is common among children and adolescents, results in significant impairments in quality of life, and places a substantial burden on healthcare systems. Despite this, there is minimal literature to guide prescribing for this population. The purpose of this article is to provide common sense prescribing recommendations for providers who treat pediatric FND.

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Background And Purpose: Paramagnetic rim lesions (PRLs) are an MRI biomarker of chronic inflammation in people with multiple sclerosis (MS). PRLs may aid in the diagnosis and prognosis of MS. However, manual identification of PRLs is time-consuming and prone to poor interrater reliability.

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Background: Health insurance in the United States varies in coverage of essential diagnostic tests, therapies, and specialists. Health disparities between privately and publicly insured patients with MS have not been comprehensively assessed. The objective of this study is to evaluate the impact of public versus private insurance on longitudinal brain outcomes in MS.

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  • Type 2 diabetes (T2D) genome-wide association studies (GWASs) typically miss rare genetic variants due to limitations in previous imputation methods and insufficient whole-genome sequencing data.
  • In a large-scale study involving over half a million individuals, researchers uncovered 12 new genetic variants linked to T2D, including a rare enhancer variant near the LEP gene that significantly increases risk.
  • The study also analyzed ClinVar variants related to monogenic diabetes, identifying additional rare variants that affect T2D risk and offering new insights into the pathogenicity of certain variants previously deemed uncertain.
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  • The study investigates how rare non-coding genetic variations affect complex traits, specifically focusing on human height by analyzing data from over 333,100 individuals across three large datasets.
  • Researchers found 29 significant rare variants linked to height, with impacts ranging from a decrease of 7 cm to an increase of 4.7 cm, after considering previously known variants.
  • The team also identified specific non-coding variants near key genes associated with height, demonstrating a new method for understanding the effects of rare variants in regulatory regions using whole-genome sequencing.
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Aims/hypothesis: Several studies have reported associations between specific proteins and type 2 diabetes risk in European populations. To better understand the role played by proteins in type 2 diabetes aetiology across diverse populations, we conducted a large proteome-wide association study using genetic instruments across four racial and ethnic groups: African; Asian; Hispanic/Latino; and European.

Methods: Genome and plasma proteome data from the Multi-Ethnic Study of Atherosclerosis (MESA) study involving 182 African, 69 Asian, 284 Hispanic/Latino and 409 European individuals residing in the USA were used to establish protein prediction models by using potentially associated cis- and trans-SNPs.

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In this study, we report a biological temperature-sensing electrical regulator in the cytochrome c oxidase of the Devil Worm, Halicephalobus mephisto. This extremophile metazoan was isolated 1.3 km underground in a South African goldmine, where it adapted to heat and potentially to hypoxia, making its mitochondrial sequence a likely target of adaptational change.

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  • The central vein sign (CVS) is a proposed biomarker for diagnosing multiple sclerosis (MS) but traditional manual ratings for assessing CVS lesions can be slow and inconsistent.
  • This study compared an automated CVS detection method to manual rating in 86 participants being evaluated for MS using 3T MRI scans.
  • Results showed the automated method had a similar effectiveness in distinguishing MS patients from non-patients as the manual methods, with an area under the curve (AUC) ranging between 0.78 and 0.89, depending on the method used.
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Objective: Airway replacement is a challenging surgical intervention and remains an unmet clinical need. Due to the risk of airway stenosis, anastomotic separation, poor vascularization, and necrosis, it is necessary to establish the gold-standard outcomes of tracheal replacement. In this study, we use a large animal autograft model to assess long-term outcomes following tracheal replacement.

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Discovery and translation of gene-environment interactions (GxEs) influencing clinical outcomes is limited by low statistical power and poor mechanistic understanding. Molecular omics data may help address these limitations, but their incorporation into GxE testing requires principled analytic approaches. We focused on genetic modification of the established mechanistic link between dietary long-chain omega-3 fatty acid (dN3FA) intake, plasma N3FA (pN3FA), and chronic inflammation as measured by high sensitivity CRP (hsCRP).

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Stimulus-specific adaptation is a hallmark of sensory processing in which a repeated stimulus results in diminished successive neuronal responses, but a deviant stimulus will still elicit robust responses from the same neurons. Recent work has established that synaptically released zinc is an endogenous mechanism that shapes neuronal responses to sounds in the auditory cortex. Here, to understand the contributions of synaptic zinc to deviance detection of specific neurons, we performed wide-field and 2-photon calcium imaging of multiple classes of cortical neurons.

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  • * We found 17 genetic loci associated with sleep duration impacting lipid levels, with 10 of them being newly identified and linked to sleep-related disturbances in lipid metabolism.
  • * The research points to potential drug targets that could lead to new treatments for lipid-related issues in individuals with sleep problems, highlighting the connection between sleep patterns and cardiovascular health.
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  • Genome-wide association studies have found numerous genetic loci linked to glycemic traits, but connecting these loci to specific genes and biological pathways remains a challenge.
  • Researchers conducted meta-analyses of exome-array studies across four glycemic traits, analyzing data from over 144,000 participants, which led to the identification of coding variant associations in more than 60 genes.
  • The study revealed significant pathways related to insulin secretion, zinc transport, and fatty acid metabolism, enhancing understanding of glycemic regulation and making data available for further research.
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One suggested approach to improve the reproductive performance of dairy herds is through the targeted management of subgroups of biologically similar animals, such as those with similar probabilities of becoming pregnant, termed pregnancy risk. We aimed to use readily available farm data to develop predictive models of pregnancy risk in dairy cows. Data from a convenience sample of 108 dairy herds in the UK were collated, and each herd was randomly allocated, at a ratio of 80:20, to either training or testing datasets.

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  • - The study investigates the use of advanced endotracheal intubation (ETI) techniques in critically ill children, as direct laryngoscopy (DL) is commonly used but not always effective.
  • - Data was collected from the National Emergency Airway Registry for Children (NEAR4KIDS) over a three-year period, excluding cases that only used DL.
  • - Advanced ETI techniques showed a 91.1% overall success rate, with video laryngoscopy being the most common method, indicating that multiple medical disciplines, including pediatric critical care and anesthesia, are involved in this process.
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Large herbivores are important components of rewilding. However, populations can grow fast: we predict that, where top-down control is insufficient, herbivores could undermine long-term rewilding goals. To avoid this, nature-mimicking interventions are required to achieve the right amount of herbivory, in the right place, at the right time through the rewilding process.

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Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes.

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We examined the associations of vegetarianism with metabolic biomarkers using traditional and genetic epidemiology. First, we addressed inconsistencies in self-reported vegetarianism among UK Biobank participants by utilizing data from two dietary surveys to find a cohort of strict European vegetarians (N = 2,312). Vegetarians were matched 1:4 with nonvegetarians for non-genetic association analyses, revealing significant effects of vegetarianism in 15 of 30 biomarkers.

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  • Women with a history of gestational diabetes mellitus (GDM) have a higher risk of developing type 2 diabetes (T2D), and researchers are exploring if genetic markers can enhance prediction of this risk.
  • The study analyzed data from 1,895 women across diverse backgrounds and found that those who developed T2D had higher polygenic risk scores (PRS), indicating a genetic predisposition for the disease.
  • Incorporating PRS into existing risk assessment models provided a slight improvement in predictive accuracy for T2D, suggesting that genetic information can be beneficial, although not drastically transformative.
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Mobility scoring data can be used to estimate the prevalence, incidence, and duration of lameness in dairy herds. Mobility scoring is often performed infrequently with variable sensitivity, but how this impacts the estimation of lameness parameters is largely unknown. We developed a simulation model to investigate the impact of the frequency and accuracy of mobility scoring on the estimation of lameness parameters for different herd scenarios.

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Shank3 is a synaptic scaffolding protein that assists in tethering and organizing structural proteins and glutamatergic receptors in the postsynaptic density of excitatory synapses. The localization of Shank3 at excitatory synapses and the formation of stable Shank3 complexes is regulated by the binding of zinc to the C-terminal sterile-alpha-motif (SAM) domain of Shank3. Mutations in the SAM domain of Shank3 result in altered synaptic function and morphology, and disruption of zinc in synapses that express Shank3 leads to a reduction of postsynaptic proteins important for synaptic structure and function.

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  • Coronary artery calcification (CAC) is linked to heart disease and assessed through a genome-wide association study (GWAS) involving 22,400 participants from various backgrounds.
  • The study confirmed connections with four known genetic loci and discovered two new loci related to CAC, with supportive replication findings for both.
  • Functional tests suggest that ARSE promotes calcification in vascular smooth muscle cells and its variants may influence CAC levels, identifying ARSE as a key target for potential treatments in vascular calcific diseases.
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