Heller in the Lower Courts

A discussion of how federal circuit courts have applied Heller, with a focus on lower court views of Heller’s holding and scope, the extent to which Heller provides a general framework for constitutional analysis in Second Amendment cases, what guidance Heller provides for resolving cases involving the right to arms in public places, the development of analytical frameworks beyond Heller, and whether lower courts have given proper deference to Heller in their Second Amendment decisions. Moderated by Professor Sarah Ludington

Mouse Papillomavirus L1 and L2 Are Dispensable for Viral Infection and Persistence at Both Cutaneous and Mucosal Tissues.

Papillomavirus L1 and L2, the major and minor capsid proteins, play significant roles in viral assembly, entry, and propagation. In the current study, we investigate the impact of L1 and L2 on viral life cycle and tumor growth with a newly established mouse papillomavirus (MmuPV1) infection model. MmuPV1 L1 knockout, L2 knockout, and L1 plus L2 knockout mutant genomes (designated as L1ATGko-4m, L2ATGko, and L1-L2ATGko respectively) were generated. The mutants were examined for their ability to generate lesions in athymic nude mice. Viral activities were examined by qPCR, immunohistochemistry (IHC), in situ hybridization (ISH), and transmission electron microscopy (TEM) analyses. We demonstrated that viral DNA replication and tumor growth occurred at both cutaneous and mucosal sites infected with each of the mutants. Infections involving L1ATGko-4m, L2ATGko, and L1-L2ATGko mutant genomes generally resulted in smaller tumor sizes compared to infection with the wild type. The L1 protein was absent in L1ATGko-4m and L1-L2ATGko mutant-treated tissues, even though viral transcripts and E4 protein expression were robust. Therefore, L1 is not essential for MmuPV1-induced tumor growth, and this finding parallels our previous observations in the rabbit papillomavirus model. Very few viral particles were detected in L2ATGko mutant-infected tissues. Interestingly, the localization of L1 in lesions induced by L2ATGko was primarily cytoplasmic rather than nuclear. The findings support the hypothesis that the L2 gene influences the expression, location, transport, and assembly of the L1 protein in vivo

Narrative Personae and Visual Signs: Reading Leonard’s intimate photo-memoir. a/b: Auto/Biography Studies.

In this paper, I look at Joanne Leonard’s Being in Pictures and engage in a critical dialogue with an assemblage of visual and textual narratives that comprise her intimate photo memoir. In doing this I draw on Hannah Arendt’s take on narratives as tangible traces of uniqueness and plurality, political traits par excellence in the cultural histories of the human condition. Being aware of my role as a reader/viewer/interpreter of a woman artist’s auto/biographical narratives, I move beyond dilemmas of representation or questions of unveiling “the real Leonard”. The artist is instead configured as a narrative persona, whose narratives respond to three interrelated themes of inquiry, namely the visualization of spatial technologies, vulnerability and the gendering of memory. Key words: gendered memories, narrative persona, spatial technologies, photo memoir, vulnerabilit

Lives saved with vaccination for 10 pathogens across 112 countries in a pre-COVID-19 world.

BackgroundVaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae, and yellow fever over the years 2000-2030 across 112 countries.MethodsTwenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios.ResultsWe estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000-2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases.ConclusionsThis study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future.FundingVIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium's modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: TBH, MJ, XL, SE-L, JT, KW, NMF, KAMG); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). We also acknowledge funding from the UK Medical Research Council and Department for International Development, which supported aspects of VIMC's work (MRC grant number: MR/R015600/1).JHH acknowledges funding from National Science Foundation Graduate Research Fellowship; Richard and Peggy Notebaert Premier Fellowship from the University of Notre Dame. BAL acknowledges funding from NIH/NIGMS (grant number R01 GM124280) and NIH/NIAID (grant number R01 AI112970). The Lives Saved Tool (LiST) receives funding support from the Bill and Melinda Gates Foundation.This paper was compiled by all coauthors, including two coauthors from Gavi. Other funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication

Evaluation of Monitoring Traps for Drosophila suzukii (Diptera: Drosophilidae) in North America

Drosophila suzukii Matsumura (Diptera: Drosophilidae), a recent invasive pest of small and stone fruits, has been detected in more than half of the U.S. states, and in Canada, Mexico, and Europe. Upon discovery, several different trap designs were recommended for monitoring. This study compared the trap designs across seven states/provinces in North America and nine crop types. Between May and November 2011, we compared a clear cup with 10 side holes (clear); a commercial trap with two side holes (commercial); a Rubbermaid container with mesh lid and rain tent (Haviland), and with 10 side holes and no tent (modified Haviland); a red cup with 10 side holes (red); and a white container with mesh lid and rain tent (Van Steenwyk). Although fly catches among traps varied per site, overall, the Haviland trap caught the most D. suzukii, followed by the red, Van Steenwyk, and clear trap. The modified Haviland and commercial trap had low captures. Among five crop types in Oregon, a clear cup with mesh sides (Dreves) also was tested and caught the most flies. Traps with greater entry areas, found in mesh traps, caught more flies than traps with smaller entry areas. In terms of sensitivity and selectivity, traps that caught more flies likewise caught flies earlier, and all traps caught 26-31% D. suzukii out of the total Drosophila captured. Future trap improvements should incorporate more entry points and focus on selective baits to improve efficiency and selectivity with regard to the seasonal behavior of D. suzukii.This is the publisher’s final pdf. The article is published by the Entomological Society of America. It can be found at: http://www.entsoc.org/Pubs/Periodicals/JE

Trap Designs for Monitoring Drosophila suzukii (Diptera: Drosophilidae)

Drosophila suzukii (Matsumura), an invasive pest of small and stone fruits, has been recently detected in 39 states of the United States, Canada, Mexico, and Europe. This pest attacks ripening fruit, causing economic losses including increased management costs and crop rejection. Ongoing research aims to improve the efficacy of monitoring traps. Studies were conducted to evaluate how physical trap features affect captures of D. suzukii. We evaluated five colors, two bait surface areas, and a top and side position for the fly entry point. Studies were conducted at 16 sites spanning seven states and provinces of North America and nine crop types. Apple cider vinegar was the standard bait in all trap types. In the overall analysis, yellow-colored traps caught significantly more flies than clear, white, and black traps; and red traps caught more than clear traps. Results by color may be influenced by crop type. Overall, the trap with a greater bait surface area caught slightly more D. suzukii than the trap with smaller area (90 vs. 40 cm²). Overall, the two traps with a side-mesh entry, with or without a protective rain tent, caught more D. suzukii than the trap with a top-mesh entry and tent.This article is the copyright property of the Entomological Society of America and may not be used for any commercial or other private purpose without specific written permission of the Entomological Society of America. This is the publisher’s final pdf. The published article can be found at: http://www.entsoc.org/Pubs/Periodicals/EE.Keywords: monitoring, spotted wing drosophila, color, vinegar fly, trap designKeywords: monitoring, spotted wing drosophila, color, vinegar fly, trap desig

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707