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IMPORTANCE: There are consistent data demonstrating that socioeconomic disadvantage is associated with risk of premature mortality, but research on the relationship between neighborhood socioeconomic factors and premature mortality is limited. Most studies evaluating the association between neighborhood socioeconomic status (SES) and mortality have used a single assessment of SES during middle to older adulthood, thereby not considering the contribution of early life neighborhood SES. OBJECTIVE: To investigate the association of life course neighborhood SES and premature mortality. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included Black and White participants of the multicenter Atherosclerosis Risk in Communities Study, a multicenter study conducted in 4 US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the northwestern suburbs of Minneapolis, Minnesota. Participants were followed up for a mean (SD) of 18.8 (5.7) years (1996-2020). Statistical analysis was performed from March 2023 through May 2024. EXPOSURE: Participants residential addresses during childhood, young adulthood, and middle adulthood were linked with US Census-based socioeconomic indicators to create summary neighborhood SES scores for each of these life epochs. Neighborhood SES scores were categorized into distribution-based tertiles. MAIN OUTCOMES AND MEASURES: Premature death was defined as all-cause mortality occurring before age 75 years. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Among 12 610 study participants, the mean (SD) age at baseline was 62.6 (5.6) years; 3181 (25.2%) were Black and 9429 (74.8%) were White; and 7222 (57.3%) were women. The lowest, compared with the highest tertile, of neighborhood SES score in middle adulthood was associated with higher risk of premature mortality (HR, 1.28; 95% CI, 1.07-1.54). Similar associations were observed for neighborhood SES in young adulthood among women (HR, 1.25; 95% CI, 1.00-1.56) and neighborhood SES in childhood among White participants (HR, 1.25; 95% CI, 1.01-1.56). Participants whose neighborhood SES remained low from young to middle adulthood had an increased premature mortality risk compared with those whose neighborhood SES remained high (HR, 1.25; 95% CI, 1.05-1.49). CONCLUSIONS AND RELEVANCE: In this study, low neighborhood SES was associated with premature mortality. The risk of premature mortality was greatest among individuals experiencing persistently low neighborhood SES from young to middle adulthood. Place-based interventions that target neighborhood social determinants of health should be designed from a life course perspective that accounts for early-life socioeconomic inequality.

We examined transposable element (TE) content of 248 placental mammal genome assemblies, the largest de novo TE curation effort in eukaryotes to date. We found that although mammals resemble one another in total TE content and diversity, they show substantial differences with regard to recent TE accumulation. This includes multiple recent expansion and quiescence events across the mammalian tree. Young TEs, particularly long interspersed elements, drive increases in genome size, whereas DNA transposons are associated with smaller genomes. Mammals tend to accumulate only a few types of TEs at any given time, with one TE type dominating. We also found association between dietary habit and the presence of DNA transposon invasions. These detailed annotations will serve as a benchmark for future comparative TE analyses among placental mammals.

The precise pattern and timing of speciation events that gave rise to all living placental mammals remain controversial. We provide a comprehensive phylogenetic analysis of genetic variation across an alignment of 241 placental mammal genome assemblies, addressing prior concerns regarding limited genomic sampling across species. We compared neutral genome-wide phylogenomic signals using concatenation and coalescent-based approaches, interrogated phylogenetic variation across chromosomes, and analyzed extensive catalogs of structural variants. Interordinal relationships exhibit relatively low rates of phylogenomic conflict across diverse datasets and analytical methods. Conversely, X-chromosome versus autosome conflicts characterize multiple independent clades that radiated during the Cenozoic. Genomic time trees reveal an accumulation of cladogenic events before and immediately after the Cretaceous-Paleogene (K-Pg) boundary, implying important roles for Cretaceous continental vicariance and the K-Pg extinction in the placental radiation.

We reconstruct the phenotype of Balto, the heroic sled dog renowned for transporting diphtheria antitoxin to Nome, Alaska, in 1925, using evolutionary constraint estimates from the Zoonomia alignment of 240 mammals and 682 genomes from dogs and wolves of the 21st century. Balto shares just part of his diverse ancestry with the eponymous Siberian husky breed. Balto's genotype predicts a combination of coat features atypical for modern sled dog breeds, and a slightly smaller stature. He had enhanced starch digestion compared with Greenland sled dogs and a compendium of derived homozygous coding variants at constrained positions in genes connected to bone and skin development. We propose that Balto's population of origin, which was less inbred and genetically healthier than that of modern breeds, was adapted to the extreme environment of 1920s Alaska.

Annotating coding genes and inferring orthologs are two classical challenges in genomics and evolutionary biology that have traditionally been approached separately, limiting scalability. We present TOGA (Tool to infer Orthologs from Genome Alignments), a method that integrates structural gene annotation and orthology inference. TOGA implements a different paradigm to infer orthologous loci, improves ortholog detection and annotation of conserved genes compared with state-of-the-art methods, and handles even highly fragmented assemblies. TOGA scales to hundreds of genomes, which we demonstrate by applying it to 488 placental mammal and 501 bird assemblies, creating the largest comparative gene resources so far. Additionally, TOGA detects gene losses, enables selection screens, and automatically provides a superior measure of mammalian genome quality. TOGA is a powerful and scalable method to annotate and compare genes in the genomic era.

Human accelerated regions (HARs) are conserved genomic loci that evolved at an accelerated rate in the human lineage and may underlie human-specific traits. We generated HARs and chimpanzee accelerated regions with an automated pipeline and an alignment of 241 mammalian genomes. Combining deep learning with chromatin capture experiments in human and chimpanzee neural progenitor cells, we discovered a significant enrichment of HARs in topologically associating domains containing human-specific genomic variants that change three-dimensional (3D) genome organization. Differential gene expression between humans and chimpanzees at these loci suggests rewiring of regulatory interactions between HARs and neurodevelopmental genes. Thus, comparative genomics together with models of 3D genome folding revealed enhancer hijacking as an explanation for the rapid evolution of HARs.

Dysregulation of the immune system and dietary patterns that increase inflammation can increase the risk for cognitive decline, but the mechanisms by which inflammatory nutritional habits may affect the development of cognitive impairment in aging are not well understood. To determine whether plasma proteins linked to inflammatory diet predict future cognitive impairment, we applied high-throughput proteomic assays to plasma samples from a subset (n = 1528) of Women's Health Initiative Memory Study (WHIMS) participants (mean [SD] baseline age, 71.3 [SD 3.8] years). Results provide insights into how inflammatory nutritional patterns are associated with an immune-related proteome and identify a group of proteins (CXCL10, CCL3, HGF, OPG, CDCP1, NFATC3, ITGA11) related to future cognitive impairment over a 14-year follow-up period. Several of these inflammatory diet proteins were also associated with dementia risk across two external cohorts (ARIC, ESTHER), correlated with plasma biomarkers of Alzheimer's disease (AD) pathology (Aβ42/40) and/or neurodegeneration (NfL), and related to an MRI-defined index of neurodegenerative brain atrophy in a separate cohort (BLSA). In addition to evaluating their biological relevance, assessing their potential role in AD, and characterizing their immune-tissue/cell-specific expression, we leveraged published RNA-seq results to examine how the in vitro regulation of genes encoding these candidate proteins might be altered in response to an immune challenge. Our findings indicate how dietary patterns with higher inflammatory potential relate to plasma levels of immunologically relevant proteins and highlight the molecular mediators which predict subsequent risk for age-related cognitive impairment.

The plasma proteomic changes that precede the onset of dementia could yield insights into disease biology and highlight new biomarkers and avenues for intervention. We quantified 4,877 plasma proteins in nondemented older adults in the Atherosclerosis Risk in Communities cohort and performed a proteome-wide association study of dementia risk over five years (n = 4,110; 428 incident cases). Thirty-eight proteins were associated with incident dementia after Bonferroni correction. Of these, 16 were also associated with late-life dementia risk when measured in plasma collected nearly 20 years earlier, during mid-life. Two-sample Mendelian randomization causally implicated two dementia-associated proteins (SVEP1 and angiostatin) in Alzheimer's disease. SVEP1, an immunologically relevant cellular adhesion protein, was found to be part of larger dementia-associated protein networks, and circulating levels were associated with atrophy in brain regions vulnerable to Alzheimer's pathology. Pathway analyses for the broader set of dementia-associated proteins implicated immune, lipid, metabolic signaling and hemostasis pathways in dementia pathogenesis.

Introduction: The distinction between coronavirus disease 2019 (COVID-19) and thyroid storm can be extremely difficult to determine on clinical grounds alone as there is significant overlap between the signs and symptoms of each.Case report: We present a case of a patient with thyroid storm triggered by underlying COVID-19 infection.Conclusion: Infection with severe acute respiratory syndrome coronavirus 2 is linked to dysregulation of the thyroid gland through numerous mechanisms, although thyroid storm triggered by COVID-19 appears rare, with only a single case previously identified in the literature.

BACKGROUND: Opioid use after bariatric surgery is not clearly understood. Few guidelines exist to inform opioid-prescribing practices after bariatric surgery. OBJECTIVE: To understand opioid use following bariatric surgery. SETTING: University hospital. METHODS: Bariatric surgery patients at a single center were prospectively surveyed at the time of their post-operative visit (January-May 2018). Patients were asked about their opioid use following surgery, whether they received education about opioid use and what they did with leftover medications. Demographic and operative details were obtained from the medical record. RESULTS: Among 33 patients, the majority (n = 29, 88%) were female with a median age of 40 (20-68) and body mass index of 44.8 (33-78.5). Most patients had leftover narcotics (n = 25, 73%). The median number of pills used was 15 (0-48). Only 12 patients (36%) thought that they had been prescribed too much pain medication. Most patients reported receiving education about expectations for post-operative pain (n = 22, 69%); few recalled education about reducing or stopping opioids (n = 13, 40%). More than half of patients (n = 17, 53%) kept their leftover opioids rather than disposing of them or bringing them to an approved turn in location. CONCLUSIONS: Despite most patients having leftover opioids following surgery, few patients recognized possible overprescription. Education regarding opioid use following surgery is inconsistent, potentially contributing to the amount of retained opioids currently available. Future guidelines should focus on determining the appropriate amount of opioids to be prescribed following surgery and standardizing and improving education given to patients.

We report our comprehensive approach to the management of patients with hypoplastic left heart syndrome (HLHS) and describe our outcomes in 100 consecutive neonates. We stratified 100 consecutive neonates (January 1, 2015 to September 1, 2023, inclusive) into 3 pathways. Pathway 1: 77 of 100 (77%) were standard risk and underwent an initial Norwood Stage 1. Pathway 2: 10 of 100 (10%) were high-risk with noncardiac risk factors and underwent an initial Hybrid Stage 1. Pathway 3: 13 of 100 (13%) were high-risk with cardiac risk factors: 10 underwent an initial Hybrid Stage 1 + Ventricular Assist Device insertion (HYBRID+VAD), and 3 were supported with prostaglandin as a planned bridge to primary cardiac transplantation. The overall 1-year mortality for the entire cohort of 100 patients was 9% (9 of 100). Pathway 1: Operative Mortality in Pathway 1 for the initial Norwood Stage 1 was 2.6% (2 of 77). Of the 75 survivors of Norwood Stage 1, 72 underwent successful Glenn, 2 underwent successful biventricular repair, and 1 underwent successful cardiac transplantation. Pathway 2: Operative Mortality in Pathway 2 for the initial Hybrid Stage 1 without VAD was 10% (1 of 10). Of 9 survivors of Hybrid Stage 1, 4 underwent successful cardiac transplantation, 1 died while awaiting cardiac transplantation, 3 underwent Comprehensive Stage 2 (with 1 Operative Mortality after Comprehensive Stage 2), and 1 underwent successful biventricular repair. Pathway 3: Of 10 patients supported with initial HYBRID+VAD in Pathway 3, 7 (70%) underwent successful cardiac transplantation and are alive today, and 3 (30%) died on VAD while awaiting transplantation. Median VAD support time was 134 days (range, 56-226 days). Of 3 patients who were bridged to transplant with prostaglandin, 2 underwent successful transplantation and 1 died while awaiting transplantation. A comprehensive approach to the management of patients with HLHS is associated with an Operative Mortality after Norwood of 2.6% (2 of 77) and an overall 1-year mortality of 9% (9 of 100). Ten patients (10%) were stabilized with HYBRID+VAD while awaiting transplantation. VAD facilitates survival on the waiting list during prolonged waiting times. [Display omitted] [ABSTRACT FROM AUTHOR]

Twenty-first-century (21 C) skills need to be taught intentionally and well, using pedagogical approaches that engage students and help them learn both skills and curriculum content. This article describes an instrumental case study of an out-of-school education programme (Bridge21) designed to help students develop 21 C skills. In order to determine the effectiveness of the programme, a mixed-methods approach was employed that included the collection of quantitative and qualitative data using student surveys (N = 329) and group interviews. A detailed skills framework was used to analyse which skills are inherent to the various activities that make up the programme. Findings suggest that the Bridge21 model can provide significant and sustained increases in student confidence across a range of skills, and that various elements of the programme design contribute directly to this.

Nutria, a semi-aquatic, South American rodent, was introduced to Maryland during the early 1940s. Originally brought to the area for fur farms, the market never established and animals were released or escaped. Nutria thrived, destroying coastal wetlands which resulted in negative environmental and economic impacts to the Chesapeake Bay region. To preserve and protect valuable wetland resources, the Chesapeake Bay Nutria Eradication Project (CBNEP) was established in 2002 through a partnership between the United States Fish and Wildlife Service, the United States Department of Agriculture’s Wildlife Services, Maryland Department of Natural Resources, and many state agencies and non-governmental organizations. Since inception, the CBNEP has removed and reduced nutria populations to near zero across ¼ million acres of wetlands throughout the Delmarva Peninsula (Maryland, Delaware, and Virginia). The CBNEP has aided in the protection of critical natural resources and provided assistance to over 400 private landowners. Throughout its history, the CBNEP has developed new detection techniques and modified existing methods as the nature of the eradication effort changed. We provide a project overview and detail several observer-based and device-based methods that were developed and used for detection of nutria including: shoreline and ground surveys, monitoring platforms, detector dogs, lure development and remote triggered cameras.

The average public school building was built around 1968 -- more than 50 years ago -- and the National Center for Education Statistics reports that half of all public schools in the United States need at least one major facility repair. Mary Filardo, Jeffrey Vincent, and Kevin Sullivan explain how poorly maintained school buildings have a negative effect on both student and teacher performance and health. Because local districts are responsible for funding their own building maintenance and upgrades, poor communities lack the resources to keep facilities in adequate shape, much less to modernize them, and needed repairs may be made using the same operating funds used to pay teachers and purchase instructional materials. The authors express hope that interest in infrastructure improvements at the federal level will enable schools to receive the funding they need.

Aim/Purpose: The main aim of this study was modeling a collaborative process for knowledge visualization, via the creation of infographics. Background: As an effective method for visualizing complex information, creating infographics requires learners to generate and cultivate a deep knowledge of content and enables them to concisely visualize and share this knowledge. This study investigates creating infographics as a knowledge visualization process for collaborative learning situations by integrating the infographic design model into the team-based and technology-mediated Bridge21 learning model. Methodology: This study was carried out using an educational design perspective by conducting three main cycles comprised of three micro cycles: analysis and exploration; design and construction; evaluation and reflection. The process and the scaffolding were developed and enhanced from cycle to cycle based on both qualitative and quantitative methods by using the infographic design rubric and researcher observations acquired during implementation. Respectively, twenty-three, twenty-four, and twenty-four secondary school students participated in the infographic creation process cycles. Contribution: This research proposes an extensive step-by-step process model for creating infographics as a method of visualization for learning. It is particularly relevant for working with complex information, in that it enables collaborative knowledge construction and sharing of condensed knowledge. Findings: Creating infographics can be an effective method for collaborative learning situations by enabling knowledge construction, visualization and sharing. The Bridge21 activity model constituted the spine of the infographic creation process. The content generation, draft generation, and visual and digital design generation components of the infographic design model matched with the investigate, plan and create phases of the Bridge21 activity model respectively. Improvements on infographic design results from cycle to cycle suggest that the revisions on the process model succeeded in their aims. The rise in each category was found to be significant, but the advance in visual design generation was particularly large. Recommendations for Practitioners: The effectiveness of the creation process and the quality of the results can be boosted by using relevant activities based on learner prior knowledge and skills. While infographic creation can lead to a focus on visual elements, the importance of wording must be emphasized. Being a multidimensional process, groups need guidance to ensure effective collaboration. Recommendation for Researchers: The proposed collaborative infographic creation process could be structured and evaluated for online learning environments, which will improve interaction and achievement by enhancing collaborative knowledge creation. Impact on Society: In order to be knowledge constructors, innovative designers, creative communicators and global collaborators, learners need to be surrounded by adequate learning environments. The infographic creation process offers them a multidimensional learning situation. They must understand the problem, find an effective way to collect information, investigate their data, develop creative and innovative perspectives for visual design and be comfortable for using digital creation tools. Future Research: The infographic creation process could be investigated in terms of required learner prior knowledge and skills, and could be enhanced by developing pre-practices and scaffolding.

ObjectiveThe complete capture of all values for each variable of interest in pharmacy research studies remains aspirational. The absence of these possibly influential values is a common problem for pharmacist investigators. Failure to account for missing data may translate to biased study findings and conclusions. Our goal in this analysis was to apply validated statistical methods for missing data to a previously analyzed data set and compare results when missing data methods were implemented versus standard analytics that ignore missing data effects.DesignUsing data from a retrospective cohort study, the statistical method of multiple imputation was used to provide regression-based estimates of the missing values to improve available data usable for study outcomes measurement. These findings were then contrasted with a complete-case analysis that restricted estimation to subjects in the cohort that had no missing values. Odds ratios were compared to assess differences in findings of the analyses. A nonadjusted regression analysis ("crude analysis") was also performed as a reference for potential bias.SettingVeterans Integrated Systems Network that includes VA facilities in the Southern California and Nevada regions.PatientsNew statin users between November 30, 2006, and December 2, 2007, with a diagnosis of dyslipidemia.Main outcome measureWe compared the odds ratios (ORs) and 95% confidence intervals (CIs) for the crude, complete-case, and multiple imputation analyses for the end points of a 25% or greater reduction in atherogenic lipids.ResultsData were missing for 21.5% of identified patients (1665 subjects of 7739). Regression model results were similar for the crude, complete-case, and multiple imputation analyses with overlap of 95% confidence limits at each end point. The crude, complete-case, and multiple imputation ORs (95% CIs) for a 25% or greater reduction in low-density lipoprotein cholesterol were 3.5 (95% CI 3.1-3.9), 4.3 (95% CI 3.8-4.9), and 4.1 (95% CI 3.7-4.6), respectively. The crude, complete-case, and multiple imputation ORs (95% CIs) for a 25% or greater reduction in non-high-density lipoprotein cholesterol were 3.5 (95% CI 3.1-3.9), 4.5 (95% CI 4.0-5.2), and 4.4 (95% CI 3.9-4.9), respectively. The crude, complete-case, and multiple imputation ORs (95% CIs) for 25% or greater reduction in TGs were 3.1 (95% CI 2.8-3.6), 4.0 (95% CI 3.5-4.6), and 4.1 (95% CI 3.6-4.6), respectively.ConclusionThe use of the multiple imputation method to account for missing data did not alter conclusions based on a complete-case analysis. Given the frequency of missing data in research using electronic health records and pharmacy claims data, multiple imputation may play an important role in the validation of study findings.

This study compares rural educational disadvantage across Australia, Canada, and New Zealand using data from the Organisation for Economic Co-operation and Development's Programme for International Student Assessment (PISA). Across the three countries, student reading literacy and school learning environments are less positive in rural communities than in urban. Furthermore, rural disadvantage in educational outcomes (reading) and opportunities is greater in Australia than Canada or New Zealand. This could be seen as surprising as student socioeconomic status (SES), typically a strong predictor of educational outcomes, is similar for rural communities in Australia and Canada, but lower in New Zealand. Rural school principals in Australia are most likely among the three countries to report that shortages of teaching personnel hinder learning. This could suggest that policies and structures can play a role in ameliorating or exacerbating rural educational disadvantage. We conclude with questions and recommendations for future research.