The influence of increased contact rate among raccoons on a nematode of public, and wildlife health concern, Baylisascar [abstract]

Abstract only availableNatural and anthropogenic fluctuations in resource availability can alter the behavioral ecology and population dynamics of wildlife. This may have unintended consequences to wildlife disease ecology, as theoretical models predict parasite transmission is highly dependent on contact rate and density of individuals within a population. We examined the influence of alterations in the behavioral ecology of hosts on the nematode Baylisascaris procyonis of raccoons, that can infect and cause disease and mortality in a variety of animals, including humans. Twelve populations of free-ranging raccoons were monitored for three years. After one year of baseline data collection, we experimentally altered the contact rate and resource availability of randomly selected populations via dispersed or clumped food distributions. Rates of contact were measured via remote cameras and host characteristics (age, sex) and infection of B. procyonis in individuals were assessed via live-capture and standard sugar flotation techniques. Prevalence of B. procyonis averaged 6.5% at three control sites (no food added; n=186 individuals), 14.3% at four sites had dispersed food additions (n=42), and 21% at five sites with clumped food additions that aggregated raccoons (n=81). The 95% confidence interval of prevalence at experimental sites did not overlap with values observed at control sites. Data collected prior to manipulation indicated that differences observed during the experiment were not due to naturally occurring differences at those sites; prevalence of B. procyonis averaged 2.3% at sites assigned to the control category, 5.4% at sites assigned to the dispersed food category, and 4.1% at sites assigned to the experimental category. These results support the hypothesis that increased rates of contact can increase transmission of parasites such as B. procyonis, and emphasize the potentially important role of anthropogenic activity in wildlife disease ecology when dealing with species that can take advantage of such resources and tolerate aggregations of conspecifics.NSF Undergraduate Mentoring in Environmental Biolog

The influence of increased contact rate among raccoons on a directly transmitted nematode, Baylisascaris procyonis [abstract]

Abstract only availableHuman encroachment on wildlife habitat can result in anthropogenic food sources that aggregate raccoons. This may have unintended consequences to wildlife and human health, as theoretical models predict parasite transmission is highly dependent on the contact rate and density of individuals within a population. We examined the influence of contact rate on a directly transmitted nematode (Baylisascaris procyonis) of raccoons that can infect and cause disease and mortality in a wide range of accidental hosts, including humans. Twelve populations of free-ranging raccoons were monitored for three years. After one year of baseline data collection, we experimentally altered the contact rate and resource availability of randomly selected populations via dispersed or clumped food distributions. Prior to manipulation, prevalence of B. procyonis averaged 9% across all sites (range 0-35%). During the experiment, prevalence of B. procyonis averaged 4% at control sites (no food added), 18% at sites that had dispersed food additions (which did not increase contact), and 22% at sites with clumped food additions that aggregated raccoons. Data collected prior to the experiment indicated that sites that were assigned to the dispersed food treatment had a naturally-occurring higher prevalence (13%) than the sites assigned to the control (5%) and aggregation treatment (9%), indicating that the high values observed in the dispersed food sites during the experiment may be due to site-specific differences rather than the addition of dispersed food. These results support the hypothesis that increased rates of contact can increase transmission of directly transmitted parasites such as B. procyonis, and emphasize the potentially important role of anthropogenic activity in the ecology of diseases when dealing with wildlife species that can take advantage of such resources and tolerate large aggregations of conspecifics

MPSoCs for Reconfigurable Modular Spacecraft

Modular, reconfigurable spacecraft offer a new approach to extending mission capability and maximising the lifetime of a spacecraft. Future uses of space robotics such as in-orbit construction and servicing allow faulty or obsolete parts of a modular spacecraft to be replaced by servicer spacecraft that dock with their targets and perform upgrades and maintenance. Such manoeuvres will require a high degree of autonomy from both platforms and thus will need to leverage high-performance onboard computing for both the robotic control and manipulation of service spacecraft but also for managing Thales Alenia Space in the UK (TAS UK) and The University of York (UoY) are involved in projects towards this goal and are collaborating to research autonomous network reconfiguration and fault tolerance of the onboard network based on existing space technology (SpaceWire, SpaceFibre). Both organisations have identified FPGA based MPSoCs as a solution for providing the high-performance computing that autonomous robotic systems require, using the FPGA fabric for mission-phase related hardware accelerators (e.g. vision soft co- processors) that can be swapped as the construction or maintenance task demands. In this presentation we will describe the modular spacecraft avionics unit that TAS UK is developing for the H2020 MOSAR project. This is based on the Xilinx Ultrascale+ MPSoC and uses the “big-little” architecture to provide a split between the spacecraft module’s mission functionality (executing on the “big” quad-core A53) and the support functions to provide: the communication network, module-to-module docking management and the module power management functions of the spacecraft (implemented on the “little” dual-core R5 cores). Details on our development of an AXI4 compatible SpaceWire and RMAP IP core will also be included. RMAP forms an important part of the MOSAR fault management strategy and this core allows processor-transparent RMAP access to the full MPSoC address range, with automatic DMA descriptors for all other SpaceWire traffic. The AXI4 interface simply allows it to be dropped into any Ultrascale+, Zynq 7000 and NG-ultra based design and several configuration options allow options such as SpW front end type (oversampling /clock recovery) and output data path width (32-bit/16bit) to be selected. We will also present details of research by the University of York on using RMAP in a MPSoC environment. Access to the full address space of a MPSoC via RMAP brings security and fault management concerns to complex SoCs and hardware security based approaches (e.g. ARM’s TrustZone) could be used in future MP- SoC architectures to protect against damage by either corrupt RMAP packets, damage from failure modes of RMAP initiators or malicious/compromised spacecraft modules. To tackle autonomy challenges UoY is cur- rently developing a reasoner based, reconfigurable modular robotic platform that can cope with uncertain environments that arise in space applications using FPGA based MPSoC and soft-processor technologies. MOSAR has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant agreement No. 821996. Part of this work is funded by EPSRC and Innovate UK under grant KTP12066

Subsequent Surgery After Revision Anterior Cruciate Ligament Reconstruction: Rates and Risk Factors From a Multicenter Cohort

BACKGROUND: While revision anterior cruciate ligament reconstruction (ACLR) can be performed to restore knee stability and improve patient activity levels, outcomes after this surgery are reported to be inferior to those after primary ACLR. Further reoperations after revision ACLR can have an even more profound effect on patient satisfaction and outcomes. However, there is a current lack of information regarding the rate and risk factors for subsequent surgery after revision ACLR. PURPOSE: To report the rate of reoperations, procedures performed, and risk factors for a reoperation 2 years after revision ACLR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 1205 patients who underwent revision ACLR were enrolled in the Multicenter ACL Revision Study (MARS) between 2006 and 2011, composing the prospective cohort. Two-year questionnaire follow-up was obtained for 989 patients (82%), while telephone follow-up was obtained for 1112 patients (92%). If a patient reported having undergone subsequent surgery, operative reports detailing the subsequent procedure(s) were obtained and categorized. Multivariate regression analysis was performed to determine independent risk factors for a reoperation. RESULTS: Of the 1112 patients included in the analysis, 122 patients (11%) underwent a total of 172 subsequent procedures on the ipsilateral knee at 2-year follow-up. Of the reoperations, 27% were meniscal procedures (69% meniscectomy, 26% repair), 19% were subsequent revision ACLR, 17% were cartilage procedures (61% chondroplasty, 17% microfracture, 13% mosaicplasty), 11% were hardware removal, and 9% were procedures for arthrofibrosis. Multivariate analysis revealed that patients aged <20 years had twice the odds of patients aged 20 to 29 years to undergo a reoperation. The use of an allograft at the time of revision ACLR (odds ratio [OR], 1.79; P = .007) was a significant predictor for reoperations at 2 years, while staged revision (bone grafting of tunnels before revision ACLR) (OR, 1.93; P = .052) did not reach significance. Patients with grade 4 cartilage damage seen during revision ACLR were 78% less likely to undergo subsequent operations within 2 years. Sex, body mass index, smoking history, Marx activity score, technique for femoral tunnel placement, and meniscal tearing or meniscal treatment at the time of revision ACLR showed no significant effect on the reoperation rate. CONCLUSION: There was a significant reoperation rate after revision ACLR at 2 years (11%), with meniscal procedures most commonly involved. Independent risk factors for subsequent surgery on the ipsilateral knee included age <20 years and the use of allograft tissue at the time of revision ACLR

Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data.

Trio-based whole-exome sequence (WES) data have established confident genetic diagnoses in ∼40% of previously undiagnosed individuals recruited to the Deciphering Developmental Disorders (DDD) study. Here we aim to use the breadth of phenotypic information recorded in DDD to augment diagnosis and disease variant discovery in probands. Median Euclidean distances (mEuD) were employed as a simple measure of similarity of quantitative phenotypic data within sets of ≥10 individuals with plausibly causative de novo mutations (DNM) in 28 different developmental disorder genes. 13/28 (46.4%) showed significant similarity for growth or developmental milestone metrics, 10/28 (35.7%) showed similarity in HPO term usage, and 12/28 (43%) showed no phenotypic similarity. Pairwise comparisons of individuals with high-impact inherited variants to the 32 individuals with causative DNM in ANKRD11 using only growth z-scores highlighted 5 likely causative inherited variants and two unrecognized DNM resulting in an 18% diagnostic uplift for this gene. Using an independent approach, naive Bayes classification of growth and developmental data produced reasonably discriminative models for the 24 DNM genes with sufficiently complete data. An unsupervised naive Bayes classification of 6,993 probands with WES data and sufficient phenotypic information defined 23 in silico syndromes (ISSs) and was used to test a "phenotype first" approach to the discovery of causative genotypes using WES variants strictly filtered on allele frequency, mutation consequence, and evidence of constraint in humans. This highlighted heterozygous de novo nonsynonymous variants in SPTBN2 as causative in three DDD probands

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

Development of the Self-Efficacy as Faculty Change Agent for Diversity (SE-FCA-D) Scale

This publication provides an overview of the development of the Self-Efficacy as Faculty Change Agent for Diversity (SE-FCA-D) scale. The 5-item scale recently appeared as an additional module on the Higher Education and Research Institute (HERI) Faculty Survey 2019-2020 for the 10 BUILD programs within the Diversity Program Consortium that are participating in the Enhance Diversity Study, supported by the National Institutes of Health (NIH U54GM119024). The piloted scale is meant to measure DPC Hallmark of Success FAC-16: “Strong self-efficacy to act as a change agent to enhance diversity in biomedical research and research training environments” (DPC, 2019). Once data are available, scale validation will move forward and findings will be shared