Development of geometric specifications for a small female anthropomorphic test device pelvis

Target surface geometry for the small female anthropomorphic test device pelvis was predicted by a statistical pelvis geometry model developed through analysis of medical imaging data. The resulting geometry was compared to the Hybrid III small female pelvis geometry and an estimate of female pelvis geometry obtained by length scaling the midsize male pelvis based on bispinous breadth. Differences were found in the shape of the pubic rami, ischial tuberosities, and anterior superior iliac wings between the small female pelvis model and the Hybrid III pelvis, which may affect interactions with seat belts and vehicle structures.National Highway Traffic Safety Administrationhttp://deepblue.lib.umich.edu/bitstream/2027.42/117574/1/103243.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/117574/4/103243-1.pdfDescription of 103243.pdf : This file has been superceded. The new file, current as of June 20, 2016, is named 103243-1.pdf.Description of 103243-1.pdf : Final report; supercedes all versions downloaded prior to June 20, 2016

Development and validation of statistical models of femur geometry for use with parametric finite element models

Statistical models from a previous study that predict male and female femur geometry as functions of age, body mass index (BMI), and femur length were updated as part of an effort to develop lower-extremity finite element models with geometries that are parametric with subject characteristics. The process for updating these models involved extracting femur geometry from clinical CT scans of an additional 8 men and 36 women (previous models used CT scans from 62 men and 36 women for a new total of 70 men and 72 women), using all of the scans for fitting a template finite element femur mesh to the surface geometry of each patient, and then programmatically determining thickness at each nodal location. Principal component analysis was then performed on the thickness and geometry nodal coordinates, and linear regression models were developed to predict principal component scores as functions of age, BMI, and femur length. The results from the updated models were compared to the previous study, and the only improvement was in the R2 value for the female models (0.74 to 0.82). The largest differences between the original models and the previous models occurred in the ends of the femur, where the largest errors in model predictions occurred.National Highway Traffic Safety Administrationhttp://deepblue.lib.umich.edu/bitstream/2027.42/116208/1/103222.pdfDescription of 103222.pdf : Final repor

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Understanding and managing the introduction pathways of alien taxa: South Africa as a case study

For the effective prevention of biological invasions, the pathways responsible for introductions must be understood and managed. However introduction pathways, particularly for developing nations, have been understudied. Using the Hulme et al. (2008) pathway classification, we assessed the South African introduction pathways in terms of the number of introductions, the invasion success of introduced taxa, how the pathways have changed over time, and how these factors vary for vertebrates, invertebrates and plants. Pathway and date of introduction, region of origin, distribution and invasion status data for 2111 alien taxa were extracted from databases. Most alien and invasive taxa were deliberately introduced and subsequently escaped captivity or cultivation. Pathway prominence also varied temporally and across organism types. Vertebrates and plants were largely escapes and although most plant escapes have become invasive, this is not the case for vertebrates. However the number of new plant and vertebrate escapes has increased over time. Invertebrates have been deliberately released or unintentionally introduced as contaminants or stowaways. For invertebrates the number of release, contaminant and stowaway introductions has increased, and most contaminants and stowaways have become invasive. As effective screening procedures are in place for invertebrates released for biological control, the major threats for South Africa are from vertebrate and plant escapes and invertebrate contaminants and stowaways. We recommend improvements to risk assessment and education to prevent escapes, and prioritised inspection strategies to reduce stowaway and contaminant introductions. Finally, as introduction pathways and introduced taxa change temporally, biosecurity decisions need to be informed by information on current and future pathways.South African National Department of Environment Affairs through its funding of the South African National Biodiversity Institute‟s Invasive Species Programme. Additional funding was provided by the DST-NRF Centre for Invasion Biology, the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa.http://link.springer.com/journal/105302017-01-30hb201

Demographic data of children included in the study distributed by isolates from middle ear fluid.

<p>Demographic data of children included in the study distributed by isolates from middle ear fluid.</p

Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations