Search

Funder: K.G.A. has received support from the American Heart Association Institute for Precision Cardiovascular Medicine (17IFUNP3384001), a KL2/Catalyst Medical Research Investigator Training (CMeRIT) award from the Harvard Catalyst (KL2 TR002542), and the NIH (1K08HL153937)., Funder: B.N.W is supported by the National Science Foundation Graduate Research Program (DGE 1256260)., Funder: I.S. is supported by a Precision Health Scholars Award from the University of Michigan Medical School., Funder: I.K., S.Ko., and K.It. are funded by the Japan Agency for Medical Research and Development, AMED, under Grant Numbers JP16ek0109070h0003, JP18kk0205008h0003, JP18kk0205001s0703, JP20km0405209, and JP20ek0109487. The BioBank Japan is supported by AMED under Grant Number JP20km0605001., Funder: J.L.M.B. acknowledges research support from NIH R01HL125863, American Heart Association (A14SFRN20840000), the Swedish Research Council (2018-02529) and Heart Lung Foundation (20170265) and the Foundation Leducq (PlaqueOmics: Novel Roles of Smooth Muscle and Other Matrix Producing Cells in Atherosclerotic Plaque Stability and Rupture, 18CVD02., Funder: P.S.dV was supported by American Heart Association grant number 18CDA34110116 and National Heart, Lung, and Blood Institute grant R01HL146860. The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I and HHSN268201700005I), R01HL087641, R01HL059367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research., Funder: O.G. has received funding from the British Heart Foundation (BHF) (FS/14/66/3129)., Funder: T.K. is supported by the Corona-Foundation (Junior Research Group Translational Cardiovascular Genomics) and the German Research Foundation (DFG) as part of the Sonderforschungsbereich SFB 1123 (B02)., Funder: D.S.A. has received support from a training grant from the NIH (T32HL007604)., Funder: N.P.B., M.C.C., J.F., and D.-K.J. have been funded by the National Institute of Diabetes and Digestive and Kidney Diseases (2UM1DK105554)., Funder: A.V.K. has been funded by 1K08HG010155 from the National Human Genome Research Institute., Funder: C.P.N. and T.R.W received funding from the British Heart Foundation (SP/16/4/32697)., Funder: The Trøndelag Health Study (The HUNT Study) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. The K.G. Jebsen Center for Genetic Epidemiology is financed by Stiftelsen Kristian Gerhard Jebsen; Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology; and Central Norway Regional Health Authority. Whole genome sequencing for the HUNT study was funded by HL109946., Funder: O.M. was funded by the Swedish Heart- and Lung Foundation, the Swedish Research Council, the European Research Council ERC-AdG-2019-885003 and Lund University Infrastructure grant ”Malmö population-based cohorts” (STYR 2019/2046)., Funder: This work was supported by the European Commission (HEALTH-F2–2013-601456) and the TriPartite Immunometabolism Consortium [TrIC]- NovoNordisk Foundation (NNF15CC0018486), VIAgenomics (SP/19/2/344612), the British Heart Foundation, a Wellcome Trust core award (M.F., H.W., 203141/Z/16/Z) and support from the NIHR Oxford Biomedical Research Centre. M.F. and H.W. are members of the Oxford BHF Centre of Research Excellence (RE/13/1/30181). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health., Funder: J.D. is a British Heart Foundation Professor, European Research Council Senior Investigator, and National Institute for Health Research (NIHR) Senior Investigator., Funder: J.C.H. acknowledges personal funding from the British Heart Foundation (FS/14/55/30806) and is a member of the Oxford BHF Centre of Research Excellence (RE/13/1/30181)., Funder: R.C. has received funding from the British Heart Foundation and British Heart Foundation Centre of Research Excellence., Funder: This research was supported by BHF (SP/13/2/30111) and conducted using the UK Biobank Resource (application number 9922)., Funder: The GerMIFs gratefully acknowledge the support of the Bavarian State Ministry of Health and Care, furthermore founded this work within its framework of DigiMed Bayern (grant No: DMB-1805-0001), the German Federal Ministry of Education and Research (BMBF) within the framework of ERA-NET on Cardiovascular Disease (Druggable-MI-genes: 01KL1802), within the scheme of target validation (BlockCAD: 16GW0198K), within the framework of the e:Med research and funding concept (AbCD-Net: 01ZX1706C), the British Heart Foundation (BHF)/German Centre of Cardiovascular Research (DZHK)-collaboration (VIAgenomics) and the German Research Foundation (DFG) as part of the Sonderforschungsbereich SFB 1123 (B02) and the Sonderforschungsbereich SFB TRR 267 (B05)., Funder: C.J.W. is funded by NIH grant R35-HL135824., Funder: This work was supported by the British Heart Foundation (BHF) grant RG/14/5/30893 (P.D.) and forms part of the research themes contributing to the translational research portfolios of the Barts Biomedical Research Centre funded by the UK National Institute for Health Research (NIHR)., The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR–Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.

The use of extinction procedures when treating escape-maintained problem behavior can be undesirable and impractical for practitioners to use. To mitigate the risks associated with escape extinction, we explored the effectiveness of a delayed reinforcement token system without the use of extinction in school and home settings to treat escape-maintained problem behavior of students with autism spectrum disorder. In lieu of escape extinction (e.g., blocking), the researchers implemented a 30 s break contingent on problem behaviors and a token (to be exchanged at the end of the session) contingent on compliance. The results of a multiple probe design indicated substantial increases in compliance and reductions in problem behavior for all four participants. These findings suggest that extinction is not necessary to eliminate escape-maintained problem behavior in children with autism.

Patients with spinal muscular atrophy (SMA) are often treated with growth friendly devices such as vertical expandable prosthetic titanium rib(VEPTR) and magnetically controlled growing rods(MCGR) to correct spinal deformity and improve pulmonary function. There is limited data on this topic, and the purpose of this study was to assess the effect of these constructs and the addition of chest wall support (CWS) on spinal deformity, thorax morphology and pulmonary outcomes. This is a retrospective analysis of prospectively collected data. We included patients with chest wall deformity and scoliosis secondary to SMA who were treated with growth friendly interventions and had two-year follow-up. Descriptive statistics and univariate analyses were performed. This study included 66 patients (25% MCGR, 73% VEPTR, 2% unknown). Approximately 23% of constructs included CWS. The average Cobb angle improved from 67° (SD: 27°) to 50° (SD: 26°) at 2 years in patients with CWS (p = 0.02), and from 59° (SD: 20°) to 46° (SD: 15°) at 2 years in patients without CWS (p

Context It is unclear whether vitamin D supplementation reduces risk of falls, and results from randomized controlled trials (RCTs) are conflicting. Objective The objective of this work is to determine whether 2000 IU/day of supplemental vitamin D3 decreases fall risk. Design VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, placebo-controlled RCT including 25 871 adults, randomly assigned November 2011 to March 2014 and treated for 5.3 years (median). Setting This is a nationwide study. Participants Men 50 years or older and women 55 years or older (mean age, 67.1 years) without cancer or cardiovascular disease at baseline participated in this study. Interventions Interventions included vitamin D3 (cholecalciferol; 2000 IU/day) and/or omega-3 fatty acids (1 g/day) or respective placebos in a 2 × 2 factorial design. Main Outcome Measures Main outcome measures include 2 or more falls and falls resulting in a doctor or hospital visit. Results Baseline serum total 25-hydroxyvitamin D (25[OH]D) level was 77 nmol/L; characteristics were well-balanced between groups. Numbers of participants with 2 or more falls were similar between active and placebo groups (9.8% vs 9.4%). Over 5 years, there were no differences in the proportion having 2 or more falls (odds ratio [OR] = 0.97; 95% CI, 0.90-1.05, P = .50), falls resulting in a doctor visit (OR = 1.03; 95% CI, 0.94-1.13, P = .46), or resulting in a hospital visit (OR = 1.04; 95% CI, 0.90-1.19, P = .61) between groups. Results did not differ between those with baseline 25(OH)D less than 50 vs 50 nmol/L or greater or other cut points. Conclusion Daily supplemental vitamin D3 vs placebo did not decrease fall risk in generally healthy adults not selected for vitamin D insufficiency. This large RCT does not indicate that supplemental vitamin D should be used for primary prevention of falls in the US population.

It is a retrospective cohort study. To compare the radiographic and clinical outcomes of serial body casting for infantile idiopathic scoliosis (IIS) with versus without the use of general anesthesia (GA). Serial body casting for IIS has traditionally been performed under GA. However, reports of neurotoxic effects of anesthetics in young children have prompted physicians to consider instead performing these procedures while patients are awake and distracted by electronic devices. Patients from a multicenter registry who underwent serial casting for IIS were included. The patients were divided into asleep (GA) and awake (no GA) cohorts. Comparisons were made between pre-casting, first in-cast, and post-casting radiographic measures in each cohort. The rates of successful casting (≥ 10° major CA improvement), curve progression, and incidence of casting abandonment for surgical intervention were also compared. One-hundred and twenty-one patients who underwent serial casting for IIS were included. Ninety-two (76%) patients were asleep during casting procedures, while 29 (24%) were awake. Patients in the awake cohort were older (p

Background The primary goal in managing early-onset scoliosis (EOS) is delaying/preventing surgical intervention while allowing improved spinal growth and chest wall and lung development to improve life expectancy. The effectiveness of serial casting for patients with neuromuscular and syndromic EOS is unclear. Methods Patients from 2 multicenter registries who underwent serial casting for nonidiopathic scoliosis (NIS) were reviewed retrospectively. Comparisons were made between precasting and postcasting major and compensatory curves and spine height. The need for surgical intervention and any treatment complications were documented. Risk factors for major curve progression from baseline to casting cessation were evaluated via univariate analysis. Results Forty-four patients (23 females; 21 males) with NIS (26 syndromic, 18 neuromuscular) and a mean age of 3.2 years at baseline were included. Mean follow-up and casting duration was 3.9 and 2.0 years, respectively. There were no statistically significant differences between mean precasting and postcasting major curve (55 vs. 60 degrees; P=0.348), minor curve (31 vs. 33 degrees; P=0.510), or rib-vertebra angle difference (18 vs. 29 degrees; P=0.840). However, thoracic height (15.5 vs. 16.8 cm; P=0.031) and lumbar height (8.9 vs. 9.8 cm; P=0.013) were significantly greater upon casting cessation. Currently, 13 patients (30%) have had successful casting (improvement of major curve ≥10 degrees) while 24 patients (55%) experienced major curve progression (worsening), and 19 patients (43%) required surgical intervention. Mean time from first casting to surgery was 34.5±15.1 months. There were no statistically significant predictors for major curve progression on univariate analysis. Conclusions Spinal deformity progression despite casting and the subsequent need for surgical intervention for NIS were significantly higher compared with those reported for idiopathic EOS. However, serial casting did afford a substantial delay in surgical intervention. Ultimately, serial casting for neuromuscular or syndromic EOS is an effective strategy for delaying surgical intervention, despite suboptimal radiographic outcomes. Level of evidence Level III.

The aim of this study is to determine risk factors for infection among EOS patients treated by rib-based distraction instrumentation, and to further assess the incidence of infection among C-EOS categories and sub-types. Despite the heterogonous nature of early onset scoliosis, the classification of early onset scoliosis (C-EOS) has proven to have excellent reliability across its major categories. C-EOS’s reliability has been verified; however, little data exist on the utility of this categorization in clinical decision-making and risk assessment. After institutional review board approval, data for EOS patients treated by rib-based distraction instrumentation were collected between 2013 and 2017 in a single institution. Data collection included: major categories of early onset scoliosis classification (etiology, major curve and kyphosis), BMI, height, weight, procedure type, site of procedure, presence of tracheostomy, and bowel/urinary incontinence. 156 EOS patients underwent 843 rib-based distraction instrumentation procedures. 22.4% of patients (35/156 patients, 42 procedures) developed infections, 30/35 requiring irrigation and debridement. Type of procedure was significantly associated with infection rate, with rib-based distraction instrumentation insertion corresponding with the highest incidence of infection, as compared to instrumentation revisions or expansions (p = 0.006). Infection rates were also more common in shorter and lighter weight children (p = 0.001 and 0.03; respectively). Patients with a neuromuscular etiology had the highest rate of infection in comparison to congenital, syndromic, and idiopathic (5.7% vs, 4.9%, 4.7%, and 2.6%; respectively). Notably, high infection rates occurred neuromuscular hyper-kyphotic subjects (M+), occurring in all major curve C-EOS subgroups and at a rate of 8.3% for all procedures. Neuromuscular, larger magnitude major curve, and larger magnitude kyphotic angle C-EOS categories appear to be at a higher risk of infection. Such information potentiates the usefulness of C-EOS in surgical decision-making and in the informed consent process. Level III therapeutic.

Plants benefit from their close association with soil microbes which assist in their response to abiotic and biotic stressors. Yet much of what we know about plant stress responses is based on studies where the microbial partners were uncontrolled and unknown. Under climate change, the soil microbial community will also be sensitive to and respond to abiotic and biotic stressors. Thus, facilitating plant adaptation to climate change will require a systems-based approach that accounts for the multi-dimensional nature of plant–microbe–environment interactions. In this perspective, we highlight some of the key factors influencing plant–microbe interactions under stress as well as new tools to facilitate the controlled study of their molecular complexity, such as fabricated ecosystems and synthetic communities. When paired with genomic and biochemical methods, these tools provide researchers with more precision, reproducibility, and manipulability for exploring plant–microbe–environment interactions under a changing climate.

Soil fungal communities vary spatially due to factors including variations in plant diversity and soil characteristics; however, the relative influences of these factors on composition and therefore function remain unclear. Small-scale variation in fungal communities may drive local variation in nutrient cycling and decomposition and may respond more to local factors compared with large climatic variations. Clarifying the roles of these factors can improve our predictions of soil fungal community and biogeochemical cycling responses to anthropogenic changes. Therefore, we examined relationships among abiotic and biotic factors and soil fungal communities associated with Quercus rubra and Pinus resinosa saplings and mature trees in a mixed-hardwood woodland. We also compared community composition and fungal enzymatic activity. Fungal community composition was associated with spatial heterogeneity of soil characteristics, while host sapling and tree species identity were poor predictors of community composition. Further, most of the compositional variation was unexplained by measured variables, suggesting stochasticity and other environmental characteristics may drive spatial variation in these communities. Additionally, enzymatic activity did not clearly correlate with fungal community composition. Overall, soil fungal communities and enzymatic activity adjacent to saplings in this woodland are influenced primarily by soil characteristics and stochasticity and not plant identity.

Price transparency purports to help patients make high-value health care decisions, however, there is little data to support this. The pediatric distal radius buckle fracture (DRBF) has 2 equally efficacious but not equally priced treatment options (cast and splint), serving as an excellent potential model for studying price transparency. This study uses the DRBF model to assess the impact of up-front cost information on a family's treatment decisions when presented with clinically equivalent treatment options for a low-risk injury.Participants age 4 to 14 presenting with an acute DRBF to a hospital-based pediatric orthopaedic clinic were recruited for this randomized controlled trial. Participants were randomized into cost-informed or cost-blind cohorts. All families received standardized information about the injury and treatment options. Cost-informed families received additional cost information. Both groups were allowed to freely choose a treatment. Families were surveyed regarding their decision factors. Cost-blinded families were subsequently presented with the cost information and could change their decision. Independent samples t tests and χ2 tests were utilized to evaluate differences.A total of 127 patients were enrolled (53% cost-informed, 47% cost-blind). The 2 groups did not significantly differ in demographics. Immobilization selection did not differ between groups, with 48% of the cost-informed families selecting the more expensive option (casting), compared with 47% of the cost-blind families. Cost was the least influential factor in the decision-making process according to participant survey, influencing only 9% of families. Only one family changed their decision after receiving cost information, from a splint to a cast.Families appear to be cost-insensitive when making medical treatment decisions for low-risk injuries for their child. Price transparency alone may not help families arrive at a decision to pursue high-value treatment in low-risk orthopaedic injuries.Level I.

Priority effects in host-associated microbiomes can influence not only community composition and structure, but also community functions, such as disease resistance. However, evidence for these priority effects remains scarce. Past studies suggest that amphibian protection from chytridiomycosis, caused by the pathogenic fungus Batrachochytrium dendrobatidis (Bd), is related to antifungal bacterial composition on host skin. Priority effects in these bacterial communities may influence susceptibility to Bd, but this possibility has not been tested. Using in vitro microcosms, we demonstrated that priority effects can influence interactions among amphibian-associated microbes. We observed strong priority effects irrespective of high antifungal ability such that the Bd-inhibitory potential of two strongly inhibitory bacterial species did not always produce higher levels of Bd-inhibition. This result suggests that interactions may be more complex than previously thought. Additionally, our results suggest that priority effects between commensal and pathogenic taxa can be either facilitatory or inhibitory, with the strength and direction of this effect dependent on the composition of the community. Thus, changes in assembly may lead to varying levels of Bd infection, influencing how we might augment amphibian-associated microbiomes to conserve taxa currently at risk of extinction.