Elk, Cervus Elaphus, Resource Selection and Implications for Anthrax Management in Southwest Montana

Anthrax, caused by the spore forming bacterium Bacillus anthracis, is a zoonotic disease that affects humans and animals throughout the world.  In North America, anthrax outbreaks occur in livestock and increasingly wildlife species.  Vaccine administration in wildlife is untenable, and the most effective form of management in wildlife is surveillance and decontamination of carcasses.  Successful management is critical, as untreated carcasses can create infectious zones increasing risk for other susceptible hosts.  This study focused on informing management in a re-emerging anthrax zone in southwest Montana.  In 2008, a large anthrax epizootic primarily affected a domestic bison, Bison bison, herd and the bull segment of a free ranging elk, Cervus elephus, herd in southwestern Montana.  Following the outbreak, we initiated a telemetry study on elk to evaluate resource selection during the anthrax season in an effort to inform anthrax management. A mixed effects generalized linear model (GLM) was used to estimate resource selection by bull elk, and habitat preferences were mapped across the landscape. Preferred habitats were overlaid on ecological niche model-based estimates of B. anthracis presence. We found significant overlap between areas with a high predicted probability of bull elk use and B. anthracis potential.  These potentially risky areas of elk and B. anthracis overlap are broadly spread over both public and private lands.  Future outbreaks in the region are probable, and this analysis identified the spatial extent of the risk area in the region, which can be used to prioritize anthrax surveillance

Examining Seasonal Anthrax Risk in Wildlife: Comparing Home Ranges and Site Fidelity in Sero-Positive and Sero-Negative Ungulates

Anthrax is frequently reported from wildlife and livestock in the US.  While useful in reducing risk in livestock, vaccination, the primary method of prevention, is untenable for free-ranging wildlife. Because of this, accurate surveillance and carcass clean-up are the most efficacious control measures for wildlife.  However, surveillance is expensive and requires significant personnel across large landscapes. Likewise, the transmission pathways are poorly understood in most species. Wildlife telemetry improves our understanding of movement patterns during risk periods. At the same time, serological surveys provide data on host exposure. Such data allow us to test hypotheses about host/pathogen interactions on the landscape. Starting in 2010, we initiated GPS telemetry and sero-prevalence studies for managed bison, Bison bison bison, and free-range elk (Cervus elaphus) in Montana. Here we will evaluate summertime home ranges in bulls from both species in western Montana. We compared home ranges and site fidelity metrics in sero-positive and sero-negative animals. Serological tests indicated that ~30% of bull elk and ~27% of unvaccinated bison were sero-positive for anthrax exposure, suggesting that low-level exposure is frequent on this landscape. Seasonal ranges can be useful for defining areas where animals may have increased likelihood of anthrax, comparing ranges to niche-based estimates of B. anthracis. Fidelity metrics suggest both species spent considerable time in niche-based high risk areas. Inter-annual data from elk suggest long-term range fidelity and overlap with high risk areas. These data can be used to prioritize surveillance efforts in those areas to maximize disease control, while managing search costs

The Association Between Persistent Poverty and Melanoma Mortality in Texas: A Retrospective Study Using Texas Cancer Registry Data

https://openworks.mdanderson.org/sumexp22/1123/thumbnail.jp

Xpert MTB/RIF Ultra for the diagnosis of HIV-associated tuberculous meningitis: a prospective validation study.

INTRODUCTION: Tuberculous meningitis accounts for 1-5% of tuberculosis cases. Diagnostic delay contributes to poor outcomes. We evaluated the performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis diagnosis. METHODS: In this prospective validation study, we tested the cerebrospinal fluid (CSF) of adults presenting with suspected meningitis (ie, headache or altered mental status with clinical signs of meningism) to the Mulago National Referral Hospital and Mbarara Regional Referral Hospital in Uganda. We centrifuged the CSF, resuspended the cell pellet in 2 mL CSF, and tested 0·5 mL aliquots with Xpert Ultra, Xpert MTB/RIF (Xpert), and mycobacterial growth indicator tube (MGIT) culture. We quantified diagnostic performance against the uniform case definition of probable or definite tuberculous meningitis and a composite microbiological reference standard. FINDINGS: From Nov 25, 2016, to Jan 24, 2019, we screened 466 adults with suspected meningitis and tested 204 for tuberculous meningitis. Uniform clinical case definition classified 51 participants as having probable or definite tuberculous meningitis. Against this uniform case definition, Xpert Ultra had 76·5% sensitivity (95% CI 62·5-87·2; 39 of 51 patients) and a negative predictive value of 92·7% (87·6-96·2; 153 of 165), compared with 55·6% sensitivity (44·0-70·4; 25 of 45; p=0·0010) and a negative predictive value of 85·8% (78·9-91·1; 121 of 141) for Xpert and 61·4% sensitivity (45·5-75·6; 27 of 44; p=0·020) and negative predictive value of 85·2% (77·4-91·1; 98 of 115) for MGIT culture. Against the composite microbiological reference standard, Xpert Ultra had sensitivity of 92·9% (80·5-98·5; 39 of 42), higher than Xpert at 65·8% (48·6-80·4; 25 of 38; p=0·0063) and MGIT culture at 72·2% (55·9-86·2; 27 of 37; p=0·092). Xpert Ultra detected nine tuberculous meningitis cases missed by Xpert and MGIT culture. INTERPRETATION: Xpert Ultra detected tuberculous meningitis with higher sensitivity than Xpert and MGIT culture in this HIV-positive population. However, with a negative predictive value of 93%, Xpert Ultra cannot be used as a rule-out test. Clinical judgment and novel highly sensitive point-of-care tests are still required. FUNDING: Wellcome Trust, National Institute of Health, National Institute of Neurologic Diseases and Stroke, Fogarty International Center, and National Institute of Allergy and Infectious Diseases

Treatment Outcomes in Adult Tuberculous Meningitis: A Systematic Review and Meta-analysis.

BACKGROUND: There is substantial variation in the reported treatment outcomes for adult tuberculous meningitis (TBM). Data on survival and neurological disability by continent and HIV serostatus are scarce. METHODS: We performed a systematic review and meta-analysis to characterize treatment outcomes for adult TBM. Following a systematic literature search (MEDLINE and EMBASE), studies underwent duplicate screening by independent reviewers in 2 stages to assess eligibility for inclusion. Two independent reviewers extracted data from included studies. We employed a random effects model for all meta-analyses. We evaluated heterogeneity by the I 2 statistic. RESULTS: We assessed 2197 records for eligibility; 39 primary research articles met our inclusion criteria, reporting on treatment outcomes for 5752 adults with TBM. The commonest reported outcome measure was 6-month mortality. Pooled 6-month mortality was 24% and showed significant heterogeneity (I 2 > 95%; P 50%. CONCLUSIONS: Mortality in adult TBM is high and varies considerably by continent and HIV status. The highest mortality is among HIV-positive adults in Sub-Saharan Africa. Standardized reporting of treatment outcomes will be essential to improve future data quality and increase potential for data sharing, meta-analyses, and facilitating multicenter tuberculosis research to improve outcomes

A Journey of Hope: giving research participants a voice to share their experiences and improve community engagement around advanced HIV disease in Uganda [version 2; peer review: 2 approved]

Over the last decade excellent progress has been made globally in HIV management thanks to antiretroviral therapy (ART) rollout and international guidelines now recommending immediate initiation of ART in people living with HIV. Despite this, advanced HIV disease (CD4 less than 200 cells/mL) and opportunistic infections remain a persistent challenge and contribute significantly to HIV-associated mortality, which equates to 23,000 deaths in Uganda in 2018 alone. Our Meningitis Research Team based in Uganda is committed to conducting clinical trials to answer important questions regarding diagnostics and management of HIV-associated opportunistic infections, including tuberculosis and cryptococcal meningitis. However, clinical research is impossible without research participants and results are meaningless unless they are translated into benefits for those affected by the disease. Therefore, we held a series of community engagement events with the aims of 1) giving research participants a voice to share their experiences of clinical research and messages of hope around advanced HIV disease with the community, 2) dispelling myths and stigma around HIV, and 3) raising awareness about the complications of advanced HIV disease and local clinical research and recent scientific advances. The purpose of this Open Letter is to describe our community engagement experience in Uganda, where we aimed to give clinical research participants a greater voice to share their experiences. These activities build upon decades of work in HIV community engagement and lays a platform for future research and engagement activities

Tuberculosis in HIV-Associated Cryptococcal Meningitis is Associated with an Increased Risk of Death.

Tuberculosis (TB) and cryptococcal meningitis are leading causes of morbidity and mortality in advanced HIV disease. Data are limited on TB co-infection among individuals with cryptococcal meningitis. We performed a retrospective analysis of HIV-infected participants with cryptococcal meningitis from 2010-2017. Baseline demographics were compared between three groups: 'prevalent TB' if TB treated >14 days prior to cryptococcal meningitis diagnosis, 'concurrent TB' if TB treated ± 14 days from diagnosis, or 'No TB at baseline'. We used time-updated proportional-hazards regression models to assess TB diagnosis as a risk for death. Of 870 participants with cryptococcal meningitis, 50 (6%) had prevalent TB, 67 (8%) had concurrent TB, and 753 (86%) had no baseline TB. Among participants without baseline TB, 67 (9%) were diagnosed with incident TB (after >14 days), with a median time to TB incidence of 41 days (IQR, 22-69). The 18-week mortality was 50% (25/50) in prevalent TB, 46% (31/67) in concurrent TB, and 45% (341/753) in the no TB group (p = 0.81). However, TB co-infection was associated with an increased hazard of death (HR = 1.75; 95% CI, 1.33-2.32; p < 0.001) in a time-updated model. TB is commonly diagnosed in cryptococcal meningitis, and the increased mortality associated with co-infection is a public health concern

A meta-analysis of the effect of antibody therapy for the prevention of severe respiratory syncytial virus infection

Abstract Background The primary objective of this meta-analytic study was to determine the impact of RSV-IGIV and palivizumab on risk of respiratory syncytial virus (RSV)-related hospitalization. Secondary objectives were to determine if antibody therapy decreases the risk of RSV infection, intensive care admission, mechanical ventilation, and mortality in high risk infant populations. Methods We performed searches of electronic data bases from 1966 to April 2009. Inclusion and exclusion criteria were defined a priori. Inclusion criteria were as follows: 1) There was randomization between polyclonal or monoclonal antibodies and placebo or no therapy, and 2) Polyclonal or monoclonal antibodies were given as prophylaxis. Results Of the six included studies, three utilized RSV-IGIV (total of 533 randomized to treatment groups) and three utilized palivizumab (total of 1,663 randomized to treatment groups). The absolute risk of hospitalization in the control arms was 12% and overall RR for all 2,196 children who received one of the antibody products was 0.53 (95% CI 0.43, 0.66), P < 0.00001. When looking only at the children who received palivizumab, the RR for hospitalization was 0.50 (95% CI 0.38, 0.66), P < 0.00001. For the children receiving RSV-IGIV, the RR for hospitalization was 0.59 (95% CI 0.42, 0.83, P < 0.002). The use of palivizumab resulted in a significant decrease in admission to the ICU (RR 0.29 (95% CI 0.14, 0.59; P = 0.0007). There was no significant reduction in the risk of mechanical ventilation or mortality with the use of antibody prophylaxis. Infants born at less than 35 weeks gestational age, and those with chronic lung and congenital heart disease all had a significant reduction in the risk of RSV hospitalization with children born under 35 weeks gestational age showing a trend towards the greatest benefit. Conclusion Both palivizumab and RSV-IGIV decrease the incidence of RSV hospitalization and ICU admission and their effect appears to be qualitatively similarly. There was neither a statistically significant reduction in the incidence of mechanical ventilation nor in all cause mortality. This meta-analysis separately quantifies the impact of RSV-IGIV and palivizumab on various measures of severe RSV disease and builds upon a previous study that was only able to examine the pooled effect of all antibody products together

Association of Hyponatremia on Mortality in Cryptococcal Meningitis: A Prospective Cohort.

BACKGROUND: Sodium abnormalities are frequent in CNS infections and may be caused by cerebral salt wasting, syndrome of inappropriate antidiuretic hormone secretion (SIADH), or medication adverse events. In cryptococcal meningitis, the prevalence of baseline hyponatremia and whether hyponatremia adversely impacts survival is unknown. METHODS: We conducted a secondary analysis of data from two randomized trials of HIV-infected adult Ugandans with cryptococcal meningitis. We grouped serum sodium into 3 categories: &amp;lt;125, 125-129, and 130-145 mmol/L. We assessed whether baseline sodium abnormalities were associated with clinical characteristics and survival. RESULTS: Of 816 participants with cryptococcal meningitis, 741 (91%) had a baseline sodium measurement available: 121 (16%) had Grade 3-4 hyponatremia (&amp;lt;125 mmol/L), 194 (26%) had Grade 2 hyponatremia (125-129 mmol/L), and 426 (57%) had a baseline sodium of 130-145 mmol/L. Hyponatremia (&amp;lt;125 mmol/L) was associated with higher initial CSF quantitative culture burden (P &amp;lt; .001), higher initial CSF opening pressure (P &amp;lt; 0.01), lower baseline Glasgow Coma Score (P &amp;lt; 0.01), and a higher percentage of baseline seizures (P = .03). Serum sodium &amp;lt;125 mmol/L was associated with increased 2-week mortality in unadjusted and adjusted survival analyses; adjusted hazard ratio of 1.87 (95%CI, 1.26 to 2.79; p &amp;lt; 0.01) compared to those with sodium 130-145 mmol/L. CONCLUSIONS: yponatremia is common in cryptococcal meningitis and is associated with excess mortality. A standardized management approach to correctly diagnose and correct hyponatremia in cryptococcal meningitis needs to be developed and tested

Teaching and Generative AI

With the rapid development of generative AI, teachers are experiencing a new pedagogical challenge, one that promises to forever change the way we approach teaching and learning. As a response to this unprecedented teaching context, this collection—Teaching and Generative AI: Pedagogical Possibilities and Productive Tensions—provides interdisciplinary teachers, librarians, and instructional designers with practical and thoughtful pedagogical resources for navigating the possibilities and challenges of teaching in an AI era. Because our goal with this edited collection is to present nuanced discussions of AI technologies across disciplines, the chapters collectively acknowledge or explore both possibilities and tensions—including the strengths, limitations, ethical considerations, and disciplinary potential and challenges—of teaching in an AI era. As such, the authors in this collection do not simply praise or criticize AI, but thoughtfully acknowledge and explore its complexities within educational settings