Home-based tuberculosis contact investigation in Uganda: a household randomised trial.

IntroductionThe World Health Organization (WHO) recommends household tuberculosis (TB) contact investigation in low-income countries, but most contacts do not complete a full clinical and laboratory evaluation.MethodsWe performed a randomised trial of home-based, SMS-facilitated, household TB contact investigation in Kampala, Uganda. Community health workers (CHWs) visited homes of index patients with pulmonary TB to screen household contacts for TB. Entire households were randomly allocated to clinic (standard-of-care) or home (intervention) evaluation. In the intervention arm, CHWs offered HIV testing to adults; collected sputum from symptomatic contacts and persons living with HIV (PLWHs) if ≥5 years; and transported sputum for microbiologic testing. CHWs referred PLWHs, children <5 years, and anyone unable to complete sputum testing to clinic. Sputum testing results and/or follow-up instructions were returned by automated SMS texts. The primary outcome was completion of a full TB evaluation within 14 days; secondary outcomes were TB and HIV diagnoses and treatments among screened contacts.ResultsThere were 471 contacts of 190 index patients allocated to the intervention and 448 contacts of 182 index patients allocated to the standard-of-care. CHWs identified 190/471 (40%) intervention and 213/448 (48%) standard-of-care contacts requiring TB evaluation. In the intervention arm, CHWs obtained sputum from 35/91 (39%) of sputum-eligible contacts and SMSs were sent to 95/190 (50%). Completion of TB evaluation in the intervention and standard-of-care arms at 14 days (14% versus 15%; difference -1%, 95% CI -9% to 7%, p=0.81) and yields of confirmed TB (1.5% versus 1.1%, p=0.62) and new HIV (2.0% versus 1.8%, p=0.90) diagnoses were similar.ConclusionsHome-based, SMS-facilitated evaluation did not improve completion or yield of household TB contact investigation, likely due to challenges delivering the intervention components

Condensing Momentum Modes in 2-d 0A String Theory with Flux

We use a combination of conformal perturbation theory techniques and matrix model results to study the effects of perturbing by momentum modes two dimensional type 0A strings with non-vanishing Ramond-Ramond (RR) flux. In the limit of large RR flux (equivalently, mu=0) we find an explicit analytic form of the genus zero partition function in terms of the RR flux $q$ and the momentum modes coupling constant alpha. The analyticity of the partition function enables us to go beyond the perturbative regime and, for alpha>> q, obtain the partition function in a background corresponding to the momentum modes condensation. For momenta such that 0<p<2 we find no obstruction to condensing the momentum modes in the phase diagram of the partition function.Comment: 22 page

Meta-Analysis Identifies Gene-by-Environment Interactions as Demonstrated in a Study of 4,965 Mice

Identifying environmentally-specific genetic effects is a key challenge in understanding the structure of complex traits. Model organisms play a crucial role in the identification of such gene-by-environment interactions, as a result of the unique ability to observe genetically similar individuals across multiple distinct environments. Many model organism studies examine the same traits but under varying environmental conditions. For example, knock-out or diet-controlled studies are often used to examine cholesterol in mice. These studies, when examined in aggregate, provide an opportunity to identify genomic loci exhibiting environmentally-dependent effects. However, the straightforward application of traditional methodologies to aggregate separate studies suffers from several problems. First, environmental conditions are often variable and do not fit the standard univariate model for interactions. Additionally, applying a multivariate model results in increased degrees of freedom and low statistical power. In this paper, we jointly analyze multiple studies with varying environmental conditions using a meta-analytic approach based on a random effects model to identify loci involved in gene-by-environment interactions. Our approach is motivated by the observation that methods for discovering gene-by-environment interactions are closely related to random effects models for meta-analysis. We show that interactions can be interpreted as heterogeneity and can be detected without utilizing the traditional uni- or multi-variate approaches for discovery of gene-by-environment interactions. We apply our new method to combine 17 mouse studies containing in aggregate 4,965 distinct animals. We identify 26 significant loci involved in High-density lipoprotein (HDL) cholesterol, many of which are consistent with previous findings. Several of these loci show significant evidence of involvement in gene-by-environment interactions. An additional advantage of our meta-analysis approach is that our combined study has significantly higher power and improved resolution compared to any single study thus explaining the large number of loci discovered in the combined study

Integrable Deformations of c^=1\hat{c}=1 Strings in Flux Backgrounds

We study d=2 0A string theory perturbed by tachyon momentum modes in backgrounds with non-trivial tachyon condensate and Ramond-Ramond (RR) flux. In the matrix model description, we uncover a complexified Toda lattice hierarchy constrained by a pair of novel holomorphic string equations. We solve these constraints in the classical limit for general RR flux and tachyon condensate. Due to the non-holomorphic nature of the tachyon perturbations, the transcendental equations which we derive for the string susceptibility are manifestly non-holomorphic. We explore the phase structure and critical behavior of the theory.Comment: 39 pages, 4 figure

Quiet Supersonic Flights 2018 (QSF18) Test: Galveston, Texas Risk Reduction for Future Community Testing with a Low-Boom Flight Demonstration Vehicle

The Quiet Supersonic Flights 2018 (QSF18) Program was designed to develop tools and methods for demonstration of overland supersonic flight with an acceptable sonic boom, and collect a large dataset of responses from a representative sample of the population. Phase 1 provided the basis for a low amplitude sonic boom testing in six different climate regions that will enable international regulatory agencies to draft a noise-based standard for certifying civilian supersonic overland flight. Phase 2 successfully executed a large scale test in Galveston, Texas, developed well documented data sets, calculated dose response relationships, yielded lessons, and identified future risk reduction activities

American College of Cardiology/American Heart Association (ACC/AHA) Class I Guidelines for the Treatment of Cholesterol to Reduce Atherosclerotic Cardiovascular Risk: Implications for US Hispanics/Latinos Based on Findings From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

BACKGROUND: The prevalence estimates of statin eligibility among Hispanic/Latinos living in the United States under the new 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol treatment guidelines are not known. METHODS AND RESULTS: We estimated prevalence of statin eligibility under 2013 ACC/AHA and 3rd National Cholesterol Education Program Adult Treatment Panel (NCEP/ATP III) guidelines among Hispanic Community Health Study/Study of Latinos (n=16 415; mean age 41 years, 40% males) by using sampling weights calibrated to the 2010 US census. We examined the characteristics of Hispanic/Latinos treated and not treated with statins under both guidelines. We also redetermined the statin-therapy eligibility by using black risk estimates for Dominicans, Cubans, Puerto Ricans, and Central Americans. Compared with NCEP/ATP III guidelines, statin eligibility increased from 15.9% (95% CI 15.0-16.7%) to 26.9% (95% CI 25.7-28.0%) under the 2013 ACC/AHA guidelines. This was mainly driven by the ≥7.5% atherosclerotic cardiovascular disease risk criteria (prevalence 13.9% [95% CI 13.0-14.7%]). Of the participants eligible for statin eligibility under NCEP/ATP III and ACC/AHA guidelines, only 28.2% (95% CI 26.3-30.0%) and 20.6% (95% CI 19.4-21.9%) were taking statins, respectively. Statin-eligible participants who were not taking statins had a higher prevalence of cardiovascular risk factors compared with statin-eligible participants who were taking statins. There was no significant increase in statin eligibility when atherosclerotic cardiovascular disease risk was calculated by using black estimates instead of recommended white estimates (increase by 1.4%, P=0.12) for Hispanic/Latinos. CONCLUSIONS: The eligibility of statin therapy increased consistently across all Hispanic/Latinos subgroups under the 2013 ACC/AHA guidelines and therefore will potentially increase the number of undertreated Hispanic/Latinos in the United States

Complement Factor H Levels Associate With Plasmodium falciparum Malaria Susceptibility and Severity.

BACKGROUND: Plasmodium falciparum may evade complement-mediated host defense by hijacking complement Factor H (FH), a negative regulator of the alternative complement pathway. Plasma levels of FH vary between individuals and may therefore influence malaria susceptibility and severity. METHODS: We measured convalescent FH plasma levels in 149 Gambian children who had recovered from uncomplicated or severe P. falciparum malaria and in 173 healthy control children. We compared FH plasma levels between children with malaria and healthy controls, and between children with severe (n = 82) and uncomplicated malaria (n = 67). We determined associations between FH plasma levels and laboratory features of severity and used multivariate analyses to examine associations with FH when accounting for other determinants of severity. RESULTS: FH plasma levels differed significantly between controls, uncomplicated malaria cases, and severe malaria cases (mean [95% confidence interval], 257 [250 to 264], 288 [268 to 309], and 328 [313 to 344] µg/mL, respectively; analysis of variance P < .0001). FH plasma levels correlated with severity biomarkers, including lactate, parasitemia, and parasite density, but did not correlate with levels of PfHRP2, which represent the total body parasite load. Associations with severity and lactate remained significant when adjusting for age and parasite load. CONCLUSIONS: Natural variation in FH plasma levels is associated with malaria susceptibility and severity. A prospective study will be needed to strengthen evidence for causation, but our findings suggest that interfering with FH binding by P. falciparum might be useful for malaria prevention or treatment

A survey of simian Plasmodium infections in humans in West Kalimantan, Indonesia

The simian parasite Plasmodium knowlesi is the predominant species causing human malaria infection, including hospitalisations for severe disease and death, in Malaysian Borneo. By contrast, there have been only a few case reports of knowlesi malaria from Indonesian Borneo. This situation seems paradoxical since both regions share the same natural macaque hosts and Anopheles mosquito vectors, and therefore have a similar epidemiologically estimated risk of infection. To determine whether there is a true cross-border disparity in P. knowlesi prevalence, we conducted a community-based malaria screening study using PCR in Kapuas Hulu District, West Kalimantan. Blood samples were taken between April and September 2019 from 1000 people aged 6 months to 85 years attending health care facilities at 27 study sites within or close to jungle areas. There were 16 Plasmodium positive samples by PCR, five human malarias (two Plasmodium vivax, two Plasmodium ovale and one Plasmodium malariae) and 11 in which no species could be definitively identified. These data suggest that, if present, simian malarias including P. knowlesi are rare in the Kapuas Hulu District of West Kalimantan, Indonesian Borneo compared to geographically adjacent areas of Malaysian Borneo. The reason for this discrepancy, if confirmed in other epidemiologically similar regions of Indonesian Borneo, warrants further studies targeting possible cross-border differences in human activities in forested areas, together with more detailed surveys to complement the limited data relating to monkey hosts and Anopheles mosquito vectors in Indonesian Borneo

Combined student ratings and self-assessment provide useful feedback for clinical teachers

Many evaluation instruments have been developed to provide feedback to physicians on their clinical teaching but written feedback alone is not always effective. We explored whether feedback effectiveness improved when teachers’ self-assessment was added to written feedback based on student ratings. 37 physicians (10 residents, 27 attending physicians) from different specialties (Internal Medicine, Surgery, Obstetrics/Gynecology, Pediatrics, Neurology, Dermatology, Ophthalmology, ENT, and Psychiatry) were invited to fill out a self-assessment questionnaire on their teaching skills. Students completed an almost identical questionnaire to evaluate the same teachers based on their experiences during clerkships. After receiving written feedback incorporating their self-assessment and the student ratings, the teachers indicated their perceptions of the self-assessment exercise and the written feedback in a questionnaire (five-point Likert scale items) and next, in more detail, in semi-structured interviews with a purposive sample of 12 of the participating teachers. 25 physicians participated (67%). The results showed that self-assessment and student feedback were both perceived as useful (3.7, SD 1.0) but the latter was considered more effective. The physicians we interviewed considered the combination of self-assessment with student ratings more effective than either self-assessment or written feedback alone. Notably, discrepancies between student ratings and self-assessment were deemed a strong incentive for change. We conclude that self-assessment can be a useful tool to stimulate improvement of clinical teaching when it is combined with written feedback based on student ratings. Future research among larger groups is needed to confirm our findings and examine whether these combined tools actually lead to improved teaching