149 research outputs found

    #MeToo & The Courts: The Impact of Social Movements on Federal Judicial Decisionmaking

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    In late 2017, the #MeToo movement swept through the United States as individuals from all backgrounds and walks of life revealed their experiences with sexual abuse and sexual harassment. After the #MeToo movement, many scholars, advocates, and policymakers posited that the watershed moment would prompt changes in the ways in which sexual harassment cases were handled. This Article examines the impact the #MeToo movement has had on judicial decisionmaking. Our hypothesis is that the #MeToo movement’s increase in public awareness and political attention to experiences of sexual misconduct should lead to more pro-claimant voting in federal courts at the district and courts of appeals levels. For district courts, we find that the probability of a pro-employee ruling in a district court increased drastically after November 1, 2017. However, while pro-employee rulings increased in district courts during the #MeToo era, pro-employee rulings decreased in circuit courts during this time period. Our findings suggest that the #MeToo movement—an extralegal social movement—impacted legal rulings that occurred in its wake before district courts but courts of appeals were more restrained in their reaction to the movement. Importantly, the law and legal standards in place during the time period of our study did not meaningfully change. In short, the #MeToo movement had a statistically significant impact on rulings from district court judges

    A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection

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    Congenital cytomegalovirus (CMV) infection is a leading cause of mental retardation and deafness in newborns. The guinea pig is the only small animal model for congenital CMV infection. A novel CMV vaccine was investigated as an intervention strategy against congenital guinea pig cytomegalovirus (GPCMV) infection. In this disabled infectious single-cycle (DISC) vaccine strategy, a GPCMV mutant virus was used that lacked the ability to express an essential capsid gene (the UL85 homolog GP85) except when grown on a complementing cell line. In vaccinated animals, the GP85 mutant virus (GP85 DISC) induced an antibody response to important glycoprotein complexes considered neutralizing target antigens (gB, gH/gL/gO, and gM/gN). The vaccine also generated a T cell response to the pp65 homolog (GP83), determined via a newly established guinea pig gamma interferon enzyme-linked immunosorbent spot assay. In a congenital infection protection study, GP85 DISC-vaccinated animals and a nonvaccinated control group were challenged during pregnancy with wild-type GPCMV (10(5) PFU). The pregnant animals carried the pups to term, and viral loads in target organs of pups were analyzed. Based on live pup births in the vaccinated and control groups (94.1% versus 63.6%), the vaccine was successful in reducing mortality (P = 0.0002). Additionally, pups from the vaccinated group had reduced CMV transmission, with 23.5% infected target organs versus 75.9% in the control group. Overall, these preliminary studies indicate that a DISC CMV vaccine strategy has the ability to induce an immune response similar to that of natural virus infection but has the increased safety of a non-replication-competent virus, which makes this approach attractive as a CMV vaccine strategy. IMPORTANCE Congenital CMV infection is a leading cause of mental retardation and deafness in newborns. An effective vaccine against CMV remains an elusive goal despite over 50 years of CMV research. The guinea pig, with a placenta structure similar to that in humans, is the only small animal model for congenital CMV infection and recapitulates disease symptoms (e.g., deafness) in newborn pups. In this report, a novel vaccine strategy against congenital guinea pig cytomegalovirus (GPCMV) infection was developed, characterized, and tested for efficacy. This disabled infectious single-cycle (DISC) vaccine strategy induced a neutralizing antibody or a T cell response to important target antigens. In a congenital infection protection study, animals were protected against CMV in comparison to the nonvaccinated group (52% reduction of transmission). This novel vaccine was more effective than previously tested gB-based vaccines and most other strategies involving live virus vaccines. Overall, the DISC vaccine is a safe and promising approach against congenital CMV infection

    Delivering a “Dose of Hope”: A Faith-Based Program to Increase Older African Americans’ Participation in Clinical Trials

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    Background: Underrepresentation of older-age racial and ethnic minorities in clinical research is a significant barrier to health in the United States, as it impedes medical research advancement of effective preventive and therapeutic strategies. Objective: The objective of the study was to develop and test the feasibility of a community-developed faith-based intervention and evaluate its potential to increase the number of older African Americans in clinical research. Methods: Using a cluster-randomized design, we worked with six matched churches to enroll at least 210 persons. We provided those in the intervention group churches with three educational sessions on the role of clinical trials in addressing health disparity topics, and those in the comparison group completed surveys at the same timepoints. All persons enrolled in the study received ongoing information via newsletters and direct outreach on an array of clinical studies seeking participants. We evaluated the short-, mid-, and longer-term effects of the interventional program on clinical trial-related outcomes (ie, screening and enrollment)

    Characterization of resistance to a potent D-peptide HIV entry inhibitor.

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    BACKGROUND: PIE12-trimer is a highly potent D-peptide HIV-1 entry inhibitor that broadly targets group M isolates. It specifically binds the three identical conserved hydrophobic pockets at the base of the gp41 N-trimer with sub-femtomolar affinity. This extremely high affinity for the transiently exposed gp41 trimer provides a reserve of binding energy (resistance capacitor) to prevent the viral resistance pathway of stepwise accumulation of modest affinity-disrupting mutations. Such modest mutations would not affect PIE12-trimer potency and therefore not confer a selective advantage. Viral passaging in the presence of escalating PIE12-trimer concentrations ultimately selected for PIE12-trimer resistant populations, but required an extremely extended timeframe (\u3e 1 year) in comparison to other entry inhibitors. Eventually, HIV developed resistance to PIE12-trimer by mutating Q577 in the gp41 pocket. RESULTS: Using deep sequence analysis, we identified three mutations at Q577 (R, N and K) in our two PIE12-trimer resistant pools. Each point mutant is capable of conferring the majority of PIE12-trimer resistance seen in the polyclonal pools. Surface plasmon resonance studies demonstrated substantial affinity loss between PIE12-trimer and the Q577R-mutated gp41 pocket. A high-resolution X-ray crystal structure of PIE12 bound to the Q577R pocket revealed the loss of two hydrogen bonds, the repositioning of neighboring residues, and a small decrease in buried surface area. The Q577 mutations in an NL4-3 backbone decreased viral growth rates. Fitness was ultimately rescued in resistant viral pools by a suite of compensatory mutations in gp120 and gp41, of which we identified seven candidates from our sequencing data. CONCLUSIONS: These data show that PIE12-trimer exhibits a high barrier to resistance, as extended passaging was required to develop resistant virus with normal growth rates. The primary resistance mutation, Q577R/N/K, found in the conserved gp41 pocket, substantially decreases inhibitor affinity but also damages viral fitness, and candidate compensatory mutations in gp160 have been identified

    Reliability of capturing foot parameters using digital scanning and the neutral suspension casting technique

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    <p>Abstract</p> <p>Background</p> <p>A clinical study was conducted to determine the intra and inter-rater reliability of digital scanning and the neutral suspension casting technique to measure six foot parameters. The neutral suspension casting technique is a commonly utilised method for obtaining a negative impression of the foot prior to orthotic fabrication. Digital scanning offers an alternative to the traditional plaster of Paris techniques.</p> <p>Methods</p> <p>Twenty one healthy participants volunteered to take part in the study. Six casts and six digital scans were obtained from each participant by two raters of differing clinical experience. The foot parameters chosen for investigation were cast length (mm), forefoot width (mm), rearfoot width (mm), medial arch height (mm), lateral arch height (mm) and forefoot to rearfoot alignment (degrees). Intraclass correlation coefficients (ICC) with 95% confidence intervals (CI) were calculated to determine the intra and inter-rater reliability. Measurement error was assessed through the calculation of the standard error of the measurement (SEM) and smallest real difference (SRD).</p> <p>Results</p> <p>ICC values for all foot parameters using digital scanning ranged between 0.81-0.99 for both intra and inter-rater reliability. For neutral suspension casting technique inter-rater reliability values ranged from 0.57-0.99 and intra-rater reliability values ranging from 0.36-0.99 for rater 1 and 0.49-0.99 for rater 2.</p> <p>Conclusions</p> <p>The findings of this study indicate that digital scanning is a reliable technique, irrespective of clinical experience, with reduced measurement variability in all foot parameters investigated when compared to neutral suspension casting.</p

    Projecting COVID-19 cases and hospital burden in Ohio

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    As the Coronavirus 2019 disease (COVID-19) started to spread rapidly in the state of Ohio, the Ecology, Epidemiology and Population Health (EEPH) program within the Infectious Diseases Institute (IDI) at The Ohio State University (OSU) took the initiative to offer epidemic modeling and decision analytics support to the Ohio Department of Health (ODH). This paper describes the methodology used by the OSU/IDI response modeling team to predict statewide cases of new infections as well as potential hospital burden in the state. The methodology has two components: (1) A Dynamical Survival Analysis (DSA)-based statistical method to perform parameter inference, statewide prediction and uncertainty quantification. (2) A geographic component that down-projects statewide predicted counts to potential hospital burden across the state. We demonstrate the overall methodology with publicly available data. A Python implementation of the methodology is also made publicly available. This manuscript was submitted as part of a theme issue on “Modelling COVID-19 and Preparedness for Future Pandemics”

    Modeling Peripheral Olfactory Coding in Drosophila Larvae

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    The Drosophila larva possesses just 21 unique and identifiable pairs of olfactory sensory neurons (OSNs), enabling investigation of the contribution of individual OSN classes to the peripheral olfactory code. We combined electrophysiological and computational modeling to explore the nature of the peripheral olfactory code in situ. We recorded firing responses of 19/21 OSNs to a panel of 19 odors. This was achieved by creating larvae expressing just one functioning class of odorant receptor, and hence OSN. Odor response profiles of each OSN class were highly specific and unique. However many OSN-odor pairs yielded variable responses, some of which were statistically indistinguishable from background activity. We used these electrophysiological data, incorporating both responses and spontaneous firing activity, to develop a Bayesian decoding model of olfactory processing. The model was able to accurately predict odor identity from raw OSN responses; prediction accuracy ranged from 12%–77% (mean for all odors 45.2%) but was always significantly above chance (5.6%). However, there was no correlation between prediction accuracy for a given odor and the strength of responses of wild-type larvae to the same odor in a behavioral assay. We also used the model to predict the ability of the code to discriminate between pairs of odors. Some of these predictions were supported in a behavioral discrimination (masking) assay but others were not. We conclude that our model of the peripheral code represents basic features of odor detection and discrimination, yielding insights into the information available to higher processing structures in the brain

    Using Satellite Tracking to Optimize Protection of Long-Lived Marine Species: Olive Ridley Sea Turtle Conservation in Central Africa

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    Tractable conservation measures for long-lived species require the intersection between protection of biologically relevant life history stages and a socioeconomically feasible setting. To protect breeding adults, we require knowledge of animal movements, how movement relates to political boundaries, and our confidence in spatial analyses of movement. We used satellite tracking and a switching state-space model to determine the internesting movements of olive ridley sea turtles (Lepidochelys olivacea) (n = 18) in Central Africa during two breeding seasons (2007-08, 2008-09). These movements were analyzed in relation to current park boundaries and a proposed transboundary park between Gabon and the Republic of Congo, both created to reduce unintentional bycatch of sea turtles in marine fisheries. We additionally determined confidence intervals surrounding home range calculations. Turtles remained largely within a 30 km radius from the original nesting site before departing for distant foraging grounds. Only 44.6 percent of high-density areas were found within the current park but the proposed transboundary park would incorporate 97.6 percent of high-density areas. Though tagged individuals originated in Gabon, turtles were found in Congolese waters during greater than half of the internesting period (53.7 percent), highlighting the need for international cooperation and offering scientific support for a proposed transboundary park. This is the first comprehensive study on the internesting movements of solitary nesting olive ridley sea turtles, and it suggests the opportunity for tractable conservation measures for female nesting olive ridleys at this and other solitary nesting sites around the world. We draw from our results a framework for cost-effective protection of long-lived species using satellite telemetry as a primary tool
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