Determining the prevalence of tuberculosis in emergency departments in the Eastern Cape region of South Africa and the utility of the World Health Organization tuberculosis screening tool

Background. South Africa (SA) faces a significant tuberculosis (TB) burden complicated by high rates of HIV-TB co-infection. In SA, emergency departments (EDs) play an important role in screening for TB.Objectives. To determine the prevalence of TB in the ED and the effectiveness of the World Health Organization (WHO) TB screening tool.Methods. This was a cross-sectional observational study, conducted in the ED at Livingstone Hospital, Port Elizabeth, from 4 June to 15 July 2018. All patients aged >18 years and able to consent were administered the WHO TB screening questions and underwent a point-of-care HIV test and demographic data collection. Patients were followed up for 1 year and tracked in the National Health Laboratory Service database to determine TB status using laboratory testing.Results. Over the study period, 790 patients were enrolled. Overall, 121 patients (15.3%) were TB-positive, with 46 (38.0%) diagnosed after presenting to the ED and 75 (62.0%) with a previous TB history determined by self-report or confirmed laboratory testing. A greater proportion of the TB-positive patients were HIV-positive (49.6%) compared with the TB-negative population (24.8%). TB-positive individuals were more likely to present to the ED with a chief complaint of shortness of breath (SoB) (18.2%) compared with the TB-negative population (10.5%). Overall, the WHO TB screening tool had poor sensitivity (46.5%) and specificity (62.5%) for identifying TB-positive patients in the ED. A multiple logistic regression analysis, controlled for age and sex, showed HIV status (odds ratio (OR) 2.81; p<0.001) and SoB (OR 2.19; p<0.05) to be significant predictors of TB positivity. Adding positive HIV status and a presenting complaint of SoB increased sensitivity to 78.3%.Conclusions. EDs in SA face a high burden of TB. While WHO screening guidelines identify some of these patients, including routine HIV testing in the ED could significantly affect the number of TB diagnoses made

Identification and Use of Frailty Indicators from Text to Examine Associations with Clinical Outcomes Among Patients with Heart Failure.

Frailty is an important health outcomes indicator and valuable for guiding healthcare decisions in older adults, but is rarely collected in a quantitative, systematic fashion in routine healthcare. Using a cohort of 12,000 Veterans with heart failure, we investigated the feasibility of topic modeling to identify frailty topics in clinical notes. Topics were generated through unsupervised learning and then manually reviewed by an expert. A total of 53 frailty topics were identified from 100,000 notes. We further examined associations of frailty with age-, sex-, and Charlson Comorbidity Index-adjusted 1-year hospitalizations and mortality (composite outcome) using logistic regression. Frailty (≤ 4 topics versu

Mitochondrial DNA data indicate an introduction through Mainland Southeast Asia for Australian dingoes and Polynesian domestic dogs

In the late stages of the global dispersal of dogs, dingoes appear in the Australian archaeological record 3500 years BP, and dogs were one of three domesticates brought with the colonization of Polynesia, but the introduction routes to this region remain unknown. This also relates to questions about human history, such as to what extent the Polynesian culture was introduced with the Austronesian expansion from Taiwan or adopted en route, and whether pre-Neolithic Australia was culturally influenced by the surrounding Neolithic world. We investigate these questions by mapping the distribution of the mtDNA founder haplotypes for dingoes (A29) and ancient Polynesian dogs (Arc1 and Arc2) in samples across Southern East Asia (n = 424) and Island Southeast Asia (n = 219). All three haplotypes were found in South China, Mainland Southeast Asia and Indonesia but absent in Taiwan and the Philippines, and the mtDNA diversity among dingoes indicates an introduction to Australia 4600–18 300 years BP. These results suggest that Australian dingoes and Polynesian dogs originate from dogs introduced to Indonesia via Mainland Southeast Asia before the Neolithic, and not from Taiwan together with the Austronesian expansion. This underscores the complex origins of Polynesian culture and the isolation from Neolithic influence of the pre-Neolithic Australian culture

Determining the prevalence of tuberculosis in emergency departments in the Eastern Cape region of South Africa and the utility of the World Health Organization tuberculosis screening tool

Background. South Africa (SA) faces a significant tuberculosis (TB) burden complicated by high rates of HIV-TB co-infection. In SA, emergency departments (EDs) play an important role in screening for TB. Objectives. To determine the prevalence of TB in the ED and the effectiveness of the World Health Organization (WHO) TB screening tool. Methods. This was a cross-sectional observational study, conducted in the ED at Livingstone Hospital, Port Elizabeth, from 4 June to 15 July 2018. All patients aged >18 years and able to consent were administered the WHO TB screening questions and underwent a point-of-care HIV test and demographic data collection. Patients were followed up for 1 year and tracked in the National Health Laboratory Service database to determine TB status using laboratory testing. Results. Over the study period, 790 patients were enrolled. Overall, 121 patients (15.3%) were TB-positive, with 46 (38.0%) diagnosed after presenting to the ED and 75 (62.0%) with a previous TB history determined by self-report or confirmed laboratory testing. A greater proportion of the TB-positive patients were HIV-positive (49.6%) compared with the TB-negative population (24.8%). TB-positive individuals were more likely to present to the ED with a chief complaint of shortness of breath (SoB) (18.2%) compared with the TB-negative population (10.5%). Overall, the WHO TB screening tool had poor sensitivity (46.5%) and specificity (62.5%) for identifying TB-positive patients in the ED. A multiple logistic regression analysis, controlled for age and sex, showed HIV status (odds ratio (OR) 2.81; p<0.001) and SoB (OR 2.19; p<0.05) to be significant predictors of TB positivity. Adding positive HIV status and a presenting complaint of SoB increased sensitivity to 78.3%. Conclusions. EDs in SA face a high burden of TB. While WHO screening guidelines identify some of these patients, including routine HIV testing in the ED could significantly affect the number of TB diagnoses made

Relationships Among Lower Body Strength, Power, and Performance of Functional Tasks

There is a large degree of variability among crewmembers with respect to decrements in muscle strength and power following long duration spaceflight, ranging from 0 to approx.30% reductions. The purpose of this study was to investigate the influence of varying decrements in lower body muscle strength and power (relative to body weight) on the performance of 2 occupationally relevant tasks (ladder climb and supine egress & walk). Seventeen participants with leg strength similar to US crewmembers performed a leg press power test, an isokinetic knee extension strength test and they were asked to complete the 2 functional tasks as quickly as possible. On additional test days the participants were asked to repeat the functional tasks under 3 conditions where a different external load was applied each time using a weighted suit in order to experimentally manipulate participants strength/body weight and power/body weight ratios. The weight in the suit ranged from 20-120% of body weight and was distributed in proportion to limb segment weights to minimize changes in center of gravity. The ladder task consisted of climbing 40 rungs on a ladder treadmill as fast as possible. The supine egress & walk task consisted of rising from a supine position and walking through an obstacle course. Results show a relatively linear relationship between strength/body weight and task time and power/body weight with task time such that the fastest performance times are associated with higher strength and power with about half the variance in task time is accounted for by a single variable (either strength or power). For the average person, a 20% reduction in power/body weight (from 18 to 14.4 W/kg) induces an increase (slowing) of about 10 seconds in the ladder climb task from 14 to 24 seconds (approx.70%) and a slowing of the supine egress & walk task from 14 to 21 seconds (approx.50%). Similar relationships were observed with strength/body weight and task performance. For the average person, a 20% reduction in strength/body weight (from 2.1 to 1.7 Nm/kg) resulted in a slowing of the ladder climb from 10.5 to 24 seconds (approx.128%) and a slowing of the supine egress & walk from 11 to 20 seconds (approx.82%). These data suggest that the single variable of either low body muscle strength or power, relative to body weight is predictive of about 50% of the variance in task performance time, and that considerable slowing in task performance is associated with relatively typical decrements in muscle performance seen with long duration spaceflight. The observation of a relatively linear relationship between strength/power and task time suggests that across the full spectrum of initial crew strengths and typical decrements in strength previously observed, that task performance would be expected to be slowed following long duration spaceflight. These data will be confirmed in actual spaceflight with subsequent studies

Behavioural responses to SARS-CoV-2 antibody testing in England: REACT-2 study

Background: This study assesses the behavioural responses to SARS-CoV-2 antibody test results as part of the REal-time Assessment of Community Transmission-2 (REACT-2) research programme, a large community-based surveillance study of antibody prevalence in England. Methods: A follow-up survey was conducted six weeks after the SARS-CoV-2 antibody test. The follow-up survey included 4500 people with a positive result and 4039 with a negative result. Reported changes in behaviour were assessed using difference-in-differences models. A nested interview study was conducted with 40 people to explore how they thought through their behavioural decisions. Results: While respondents reduced their protective behaviours over the six weeks, we did not find evidence that positive test results changed participant behaviour trajectories in relation to the number of contacts the respondents had, for leaving the house to go to work, or for leaving the house to socialise in a personal place. The qualitative findings supported these results. Most people did not think that they had changed their behaviours because of their test results, however they did allude to some changes in their attitudes and perceptions around risk, susceptibility, and potential severity of symptoms. Conclusions: We found limited evidence that knowing your antibody status leads to behaviour change in the context of a research study. While this finding should not be generalised to widespread self-testing in other contexts, it is reassuring given the importance of large prevalence studies, and the practicalities of doing these at scale using self-testing with lateral flow immunoassay (LFIA)

Development of mPing-based activation tags for crop insertional mutagenesis

Modern plant breeding increasingly relies on genomic information to guide crop improvement. Although some genes are characterized, additional tools are needed to effectively identify and characterize genes associated with crop traits. To address this need, the mPing element from rice was modified to serve as an activation tag to induce expression of nearby genes. Embedding promoter sequences in mPing resulted in a decrease in overall transposition rate; however, this effect was negated by using a hyperactive version of mPing called mmPing20. Transgenic soybean events carrying mPing-based activation tags and the appropriate transposase expression cassettes showed evidence of transposition. Expression analysis of a line that contained a heritable insertion of the mmPing20F activation tag indicated that the activation tag induced overexpression of the nearby soybean genes. This represents a significant advance in gene discovery technology as activation tags have the potential to induce more phenotypes than the original mPing element, improving the overall effectiveness of the mutagenesis system

Tuberous sclerosis complex exhibits a new renal cystogenic mechanism

Tuberous sclerosis complex (TSC) is a tumor predisposition syndrome with significant renal cystic and solid tumor disease. While the most common renal tumor in TSC, the angiomyolipoma, exhibits a loss of heterozygosity associated with disease, we have discovered that the renal cystic epithelium is composed of type A intercalated cells that have an intact Tsc gene that have been induced to exhibit Tsc‐mutant disease phenotype. This mechanism appears to be different than that for ADPKD. The murine models described here closely resemble the human disease and both appear to be mTORC1 inhibitor responsive. The induction signaling driving cystogenesis may be mediated by extracellular vesicle trafficking.TSC renal cystic disease develops in about half of the patients. The disease appears to caused by an induction mechanism such that a small population of mutant cells can cause significant renal cystic disease comprised of mostly genetically normal cells.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147796/1/phy213983.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147796/2/phy213983_am.pd

Heterogeneity of HIV incidence : a comparative analysis between fishing communities and in a neighbouring rural general population, Uganda, and implications for HIV control

Objectives To describe HIV heterogeneity in rural Uganda using incidence data collected between January 2012 and December 2014 among fishing cohort (FC) and in an adjacent rural general population cohort (GPC). Methods In the FC, eligible HIV high-risk adults aged 18+ years were enrolled, followed and HIV tested every 3 months. Demographic and sexual behaviour data were also collected. The GPC, approximately 47 km away from the FC, was followed through annual surveys, and sociodemographic and behavioural data collected. A subset of GPC with comparable risk profiles to the FC was selected. We presented sociodemographic and risk profiles and also computed stratified HIV incidence. Cox regression was used to assess factors associated with HIV incidence. Results Overall HIV incidence was higher in the FC than in the ‘high-risk’ GPC, 6.04 and 0.56 per 100 person years at risk, respectively, with a rate ratio (RR) of 10.83 (95% CI 6.11 to 19.76). This was higher among those aged 18–24 years, unmarried and those with more than two sex partners in the past year, RR of 15.44, 22.99 and 19.29, respectively. In the FC, factors associated with high incidence in multivariate analysis were duration in the community and unprotected sex. The factors in the GPC were ethnicity, marital status and duration in the community. Conclusions We have observed a substantial heterogeneity in HIV incidence. The high incidence in fishing communities is contributing greatly to the overall HIV burden in Uganda, and thus urgent combination prevention efforts are needed towards national goal to reduce HIV epidemic

Antibody attributes that predict the neutralization and effector function of polyclonal responses to SARS-CoV-2

BACKGROUND: While antibodies can provide significant protection from SARS-CoV-2 infection and disease sequelae, the specific attributes of the humoral response that contribute to immunity are incompletely defined. METHODS: We employ machine learning to relate characteristics of the polyclonal antibody response raised by natural infection to diverse antibody effector functions and neutralization potency with the goal of generating both accurate predictions of each activity based on antibody response profiles as well as insights into antibody mechanisms of action. RESULTS: To this end, antibody-mediated phagocytosis, cytotoxicity, complement deposition, and neutralization were accurately predicted from biophysical antibody profiles in both discovery and validation cohorts. These models identified SARS-CoV-2-specific IgM as a key predictor of neutralization activity whose mechanistic relevance was supported experimentally by depletion. CONCLUSIONS: Validated models of how different aspects of the humoral response relate to antiviral antibody activities suggest desirable attributes to recapitulate by vaccination or other antibody-based interventions