Miracle-dz/UniFAR-FTUs huggingface dataset:
Projecting the clinical benefits and risks of using efavirenz-containing antiretroviral therapy regimens in women of childbearing age

Objectives:To project the outcomes of using either efavirenz or nevirapine as part of initial antiretroviral therapy (ART) in women of childbearing age in Côte d’Ivoire. Methods:We used an HIV computer simulation model to project both the mother's survival and the birth defects at 10 years for a cohort of women who started ART with either efavirenz or nevirapine. The primary outcome was the ratio at 10 years of the difference in the number of women alive to the difference in the cumulative number of birth defects in women who started ART with efavirenz compared with nevirapine. In the base case analysis, the birth defect rate was 2.9% on efavirenz and 2.7% on nevirapine. In sensitivity analyses, we varied all inputs across confidence intervals reported in the literature. Results:In the base case analysis, for a cohort of 100 000 women, the additional number of women alive initiating ART with efavirenz at 10 years was 15 times the additional number of birth defects (women alive: nevirapine 67 969, efavirenz 68 880, difference = 911; birth defects: nevirapine 1128, efavirenz 1187, difference = 59). In sensitivity analysis, the teratogenicity rate with efavirenz had to be 6.3%, or 2.3 times higher than the rate with nevirapine, for the excess number of birth defects to outweigh the additional number of women alive at 10 years. Conclusion:In Côte d’Ivoire, initiating ART with efavirenz instead of nevirapine is likely to substantially increase the number of women alive at 10 years with a smaller potential number of birth defects.
Möglichkeiten des Hörerhalts bei Labyrinth-Fisteln von unterschiedlichem Schweregrad

The labyrinthine fistula continues to be one of the most common complications in ears with cholesteatoma. Fifty-one patients with labyrinthine fistula were identified in a series of 1243 cases with cholesteatoma operated upon between 1989 and 1993 at the University ENT Clinic Wuerzburg. The surgical management concept comprised of removing the cholesteatoma matrix, categorizing the fistula type, and immediate covering of the labyrinthine capsule defect with bone dust, perichondrium and fibrin glue. The classification system of the fistulae used in the study used the depth of labyrinthine involvement as a criterion and also took into account the possibility of intentional or accidental damage to the labyrinth during surgical manipulation (Fig. 1). From 1991 on, patients were treated with 500 mg of Presnisolon 21 hydrogen succinate in a single intravenous dose, at the time the fistula was corrected. The postoperative hearing results were graded based on the extend of preservation of inner ear function at or near the preoperative level. None of the patients who had corticosteroid therapy suffered a profound sensory neural hearing loss (Fig. 2, 3), whereas five ears without steroids and a deep fistula lost function completely. The study concluded that corticosteroids have a beneficial impact on postoperative outcome in cases with severe injury to the membranous labyrinth.
Antiviral Activity, Pharmacokinetics, and Safety of the HIV-1 Protease Inhibitor TMC310911, Coadministered With Ritonavir, in Treatment-Naive HIV-1–Infected Patients

Objectives:TMC310911 is a novel HIV type-1 (HIV-1) protease inhibitor with broad in vitro antiviral activity. In this phase 2a, open-label randomized study, the antiviral activity, pharmacokinetics, and safety and tolerability of ritonavir-boosted TMC310911 was assessed. Methods:In this study, treatment-naive HIV-1 patients (aged 18–60 years) received 1 of the 4 dosing regimens of TMC310911: 150 mg twice-daily (bid) (n = 8), 300 mg bid (n = 8), 75 mg bid (n = 9), or 300 mg once-daily (qd) (n = 8), for 14 days, all coadministered with 100 mg of ritonavir, as only antiretroviral therapy. Results:The mean change from baseline in HIV-1 RNA (log10 copies per milliliter; primary efficacy endpoint) was −1.30 (75 mg bid), −1.14 (150 mg bid), −1.07 (300 mg bid), and −1.06 (300 mg qd) on day 8 and −1.53 (75 mg bid), −1.79 (150 mg bid), −1.69 (300 mg bid), and −1.55 (300 mg qd) on day 15. At steady state (day 14), the mean maximum plasma concentration and mean area under the plasma concentration–time curve from 0 to 12 hours tended to increase dose proportionally for bid doses; TMC310911 daily exposures for the 300 mg qd treatment and 150 mg bid treatment were comparable. The most common (≥10%) treatment-emergent adverse events were fatigue (27.3%) and nausea (12.1%); no deaths or serious treatment-emergent adverse events were reported in this study. Conclusions:Combination treatment with TMC310911 and ritonavir showed potent antiviral activity (>1.5 log10 copies/mL decrease in plasma HIV-1 RNA) at all evaluated doses, and treatment was generally safe and well tolerated.
Multicenter, Randomized Trial Assessing the Effectiveness and Safety of Calcium Hydroxylapatite for Hand Rejuvenation

OBJECTIVE To assess the safety and effectiveness of calcium hydroxylapatite (Radiesse Dermal Filler; RDF) for hand rejuvenation. METHODOLOGY One hundred and one randomized patients received RDF in the hands or no treatment (controls) for 3 months. Controls were crossed over at 3 months, and all patients were followed for 12 months. Assessments include the Busso Hand Volume Severity Scale (BHVSS), Global Aesthetic Improvement Scale‐Revised (GAIS‐R), patient satisfaction, physician satisfaction, hand function, and safety. RESULTS At 3 months and 6 months, 66% and 56% of hands, respectively, showed at least a 1‐point improvement on the BHVSS. At the same time points, 89% and 75% of hands, respectively, were improved on the GAIS‐R. In the controlled analysis, treated hands were statistically better than controls. At 3 and 6 months, 86% and 88% of physicians, respectively, and 78% and 76% of patients, respectively, were satisfied; 66% indicated likelihood to return for future RDF treatments. Treatment did not affect hand function. Adverse events were generally short in duration and without serious complications. CONCLUSIONS Hands treated with RDF showed statistically and clinically significant improvement, with high patient and physician satisfaction and no serious adverse events. BioForm Medical (San Mateo, CA) provided the Radiesse soft tissue filler, funding, supplies and equipment for photographic documentation for this study. Dr. Mariano Busso owns shares in BioForm Medical, Inc, is a member of the company's Medical Education Faculty, and has received compensation for presentations about Radiesse to the medical community. Dr. Marion Moers‐Carpi owns no stock in BioForm but has received compensation for presentations about Radiesse to the medical community. The remaining physicians have nothing to disclose. David J. Howell, PhD, RRT (San Francisco, CA) provided assistance with editorial development of this manuscript.
DO AGRICULTURAL CHEMICALS CAUSE SOFT TISSUE SARCOMA? INITIAL FINDINGS OF A CASE-CONTROL STUDY IN NEW ZEALAND

Swedish studies have indicated that persons exposed to chlorophenols and phenoxyherbicide sprays, including 2,4,5-T, may be at increased risk of developing soft tissue sarcoma (STS). In addition, several cases of STS have been reported among industrial workers manufacturing 2,4,5-T and related compounds. This paper reports initial findings from a case-control study of 102 male STS patients appearing on the New Zealand Cancer Registry between 1976 and 1980, with 306 controls chosen from patients with other forms of cancer and matched by age and year of registration. Occupation as reported at the time of cancer registration was compared between the two groups. No excess appeared for the occupational group involving agriculture and forestry in spite of the fact that phenoxyherbicides have been used extensively for many years in New Zealand in agriculture and forestry. While a more definitive conclusion concerning the relationship between chemical exposures and STS must await analysis of patient interviews, the findings so far suggest that even if phenoxyherbicides and chlorophenols cause STS, only a small proportion of cases could be attributed to such chemicals in New Zealand.
Exploring the Effect of Sex on Empirical Fitness Landscapes

The nature of epistasis has important consequences for the evolutionary significance of sex and recombination. Recent efforts to find negative epistasis as a source of negative linkage disequilibrium and associated long‐term advantage to sex have yielded little support. Sign epistasis, where the sign of the fitness effects of alleles varies across genetic backgrounds, is responsible for the ruggedness of the fitness landscape, with several unexplored implications for the evolution of sex. Here, we describe fitness landscapes for two sets of strains of the asexual fungus Aspergillus niger involving all combinations of five mutations. We find that ∼30% of the single‐mutation fitness effects are positive despite their negative effect in the wild‐type strain and that several local fitness maxima and minima are present. We then compare adaptation of sexual and asexual populations on these empirical fitness landscapes by using simulations. The results show a general disadvantage of sex on these rugged landscapes, caused by the breakdown by recombination of genotypes on fitness peaks. Sex facilitates movement to the global peak only for some parameter values on one landscape, indicating its dependence on the landscape’s topography. We discuss possible reasons for the discrepancy between our results and the reports of faster adaptation of sexual populations.
Diagnostic Delays and Clinical Decision Making With Centralized Xpert MTB/RIF Testing in Durban, South Africa

Setting:We conducted a retrospective study among HIV-infected adult suspects (≥18 years) with pulmonary tuberculosis (TB), who underwent Xpert MTB/RIF (Xpert) testing at McCord Hospital and its adjoining HIV clinic in Durban, South Africa. Objective:To determine if Xpert testing performed at a centralized laboratory accelerated time to TB diagnosis. Design:We obtained data on sputum smear microscopy [acid-fast bacilli (AFB)], Xpert, and the rationale for treatment initiation from medical records. The primary outcome was “total diagnostic time,” defined as time from sputum collection to clinicians' receipt of results. A linear mixed-effect model compared the duration of steps in the diagnostic pathway across testing modalities. Results:Among 403 participants, the median “total diagnostic time” for AFB and Xpert was 3.3 and 6.4 days, respectively (P < 0.001). When compared with AFB, the median delay for Xpert “laboratory processing” was 1.4 days (P < 0.001) and “result transfer to clinic” was 1.7 days (P < 0.001). Among 86 Xpert-positive participants who initiated treatment, 49 (57%) started treatment based on clinical suspicion or AFB-positive results, whereas only 32 (37%) started treatment based on Xpert-positive results. Conclusions:In our setting, Xpert results took twice as long as AFB results to reach clinicians. Replacing AFB with centralized Xpert may delay TB diagnoses in some settings.
A Mechanistic Model to Study the Thermal Ecology of a Southeastern Pacific Dominant Intertidal Mussel and Implications for Climate Change

Developing mechanistic models to predict an organism’s body temperature facilitates the study of physiological stresses caused by extreme climatic conditions the species might have faced in the past or making predictions about changes to come in the near future. Because the models combine empirical observation of different climatic variables with essential morphological attributes of the species, it is possible to examine specific aspects of predicted climatic changes. Here, we develop a model for the competitively dominant intertidal mussel Perumytilus purpuratus that estimates body temperature on the basis of meteorological and tidal data with an average difference (±SE) of 0.410° ± 0.0315°C in comparison with a field‐deployed temperature logger. Modeled body temperatures of P. purpuratus in central Chile regularly exceeded 30°C in summer months, and values as high as 38°C were found. These results suggest that the temperatures reached by mussels in the intertidal zone in central Chile are not sufficiently high to induce significant mortality on adults of this species; however, because body temperatures >40°C can be lethal for this species, sublethal effects on physiological performance warrant further investigation. Body temperatures of mussels increased sigmoidally with increasing tidal height. Body temperatures of individuals from ∼70% of the tidal range leveled off and did not increase any further with increasing tidal height. Finally, body size played an important role in determining body temperature. A hypothetical 5‐cm‐long mussel (only 1 cm longer than mussels found in nature) did reach potentially lethal body temperatures, suggesting that the biophysical environment may play a role in limiting the size of this small species.
0351 G-estimation: why does it work and what does it offer?

Objectives Standard data analysis procedures provide biassed answers to etiologic questions in occupational studies. G-estimation is an alternative that allows researchers to avoid healthy worker survivor bias, and its results can be expressed as estimates of the impacts of hypothetical policy interventions. Method Rather than estimating the association between observed exposure and observed outcome, g-estimation models the counterfactual outcomes under no exposure as a function of observed outcomes and exposures. Adjustment for confounders is achieved by predicting exposure conditional on those confounders and on the counterfactual outcome. The method leverages the assumption that all confounders are measured: within strata of the measured confounders, observed exposure is “randomised”--that is, statistically independent of counterfactual outcome. This allows for correct adjustment for time-varying confounders affected by prior exposure and thus avoids healthy worker survivor bias. Results Results can be expressed in terms of the impacts of hypothetical exposure limits. For example, after g-estimation of an accelerated failure time model, counterfactual survival times under a series of specified exposure limits can each be compared to observed survival time. This allows the researcher to report estimates of the total number of years of life that could have been saved by enforcing each limit. Conclusions G-estimation is a valuable tool for occupational epidemiologists because it can both prevent bias due to the healthy worker survivor effect and estimate the impacts of hypothetical exposure limits.
The effect of external ankle support in chronic lateral ankle joint instability

We examined the effect of ankle taping on ankle joint stability by measuring mechanical stability using stand ardized stress radiographs. Anterior talar translation and talar tilt, both with and without ankle tape, were examined. The reduction of anterior talar translation and talar tilt with tape as compared to without tape was insignificant. The reaction time of the peroneus muscles was measured by electromyographic signal after a simulated ankle sprain on a tilting trapdoor. The reaction time was significantly slower in the unstable ankles of 20 athletes with unilateral ankle instability than in the stable contra lateral ankles. With tape, the reaction time was signifi cantly shortened, although not back to normal. The greatest improvement in reaction time was achieved in ankles with the highest degree of mechanical instability. Thus, the mechanism behind the function of ankle tape may be to restrict the extremes of ankle motion and to help shorten the reaction time of the peroneus muscles by affecting the proprioceptive function of the ankle.
Genetic Variation Promotes Long‐Term Coexistence of Brassica nigra and Its Competitors

How multiple species coexist in the face of limiting resources remains one of the central questions in ecology. Recent theoretical and empirical studies have documented the importance of evolutionary forces in species coexistence. However, there remains a disconnect between these two approaches, as empirical studies are generally too short to explore long‐term coexistence and theoretical studies are rarely specific enough to allow for meaningful comparisons with natural systems. Here I combine field data with simulation modeling to test how a genetic trade‐off between intra‐ and interspecific competitive ability alters the long‐term coexistence of plant species. In two of the three species combinations tested, coexistence was possible only in models that included evolutionary processes. Additionally, genetic variation and the resultant evolutionary change allowed for coexistence under a much wider range of ecological conditions by both increasing equalizing (neutral) effects and providing a novel evolutionary stabilizing (niche) effect. Biodiversity is declining at both the species and the genetic levels. These results suggest that conserving species diversity may depend critically on our ability to conserve the genetic diversity within species.
Hair follicle melanocyte precursors are awoken by ultraviolet radiation via a cell extrinsic mechanism

Melanocyte stem cells (MCSCs) in the upper portion of the hair follicle periodically supply melanocytes (MCs) that migrate downward into the hair bulb during anagen, the growth phase of the hair cycle. However MCs can also migrate upwards. We previously observed an increase in epidermal MC density in the mouse epidermis after a single ultraviolet radiation (UVR) exposure in neonatal, but not adult mice. To better understand MCSC activation by UVR we methodically studied the response of MCs to narrow band UVB (since UVA does not invoke this response) exposure in neonatal mice, and in adults at different stages of the hair cycle. We found that a single exposure of adult mice did not induce activation of MCSCs, in any stage of the hair cycle. When adult mice MCSCs were isolated in telogen, multiple UVB exposures resulted in their activation and production of daughter cells, which migrated upwards to the epidermis. Importantly, the MCSCs produced new progeny without themselves having incurred DNA damage after UVB exposure. This, together with examination of MC localisation in the skin of mice overexpressing stem cell factor in their keratinocytes, leads us to conclude that MCSC activation by UVB is driven via paracrine production of either SCF and/or other keratinocyte cytokines. We re-examined the increase in epidermal MC density in neonatal mouse skin. This effect was much more profound after only a single exposure than that of even multiple exposures to adult skin, and we show that in this setting also, the epidermal MCs mostly derive from activation of MC precursors in the upper hair follicle, and most likely via a cell extrinsic mechanism. Hence, although adaptive changes in the skin induced by repetitive UVB exposures are necessary in adult mice, in both the adult and neonatal context the division and migration upwards of follicular MCSCs is the major mode by which epidermal MC numbers increase after UVR exposure.
High Interest in Preexposure Prophylaxis Among Men Who Have Sex With Men at Risk for HIV Infection: Baseline Data From the US PrEP Demonstration Project

Background:Preexposure prophylaxis (PrEP) is the first biomedical intervention with proven efficacy to reduce HIV acquisition in men who have sex with men (MSM) and transgender women. Little is known about levels of interest and characteristics of individuals who elect to take PrEP in real-world clinical settings. Methods:The US PrEP Demonstration Project is a prospective open-label cohort study assessing PrEP delivery in municipal sexually transmitted disease clinics in San Francisco and Miami and a community health center in Washington, DC. HIV-uninfected MSM and transgender women seeking sexual health services at participating clinics were assessed for eligibility and offered up to 48 weeks of emtricitabine/tenofovir for PrEP. Predictors of enrollment were assessed using a multivariable Poisson regression model, and characteristics of enrolled participants are described. Results:Of 1069 clients assessed for participation, 921 were potentially eligible and 557 (60.5%) enrolled. In multivariable analyses, participants from Miami (adjusted Relative Risk [aRR]: 1.53; 95% confidence interval [CI]: 1.33 to 1.75) or DC (aRR: 1.33; 95% CI: 1.2 to 1.47), those who were self-referred (aRR: 1.48; 95% CI: 1.32 to 1.66), those with previous PrEP awareness (aRR: 1.56; 95% CI: 1.05 to 2.33), and those reporting >1 episode of anal sex with an HIV-infected partner in the last 12 months (aRR: 1.20; 95% CI: 1.09 to 1.33) were more likely to enroll. Almost all (98%) enrolled participants were MSM, and at baseline, 63.5% reported condomless receptive anal sex in the previous 3 months. Conclusions:Interest in PrEP is high among a diverse population of MSM at risk for HIV infection when offered in sexually transmitted disease and community health clinics.
Impact of Cotrimoxazole and Insecticide-Treated Nets for Malaria Prevention on Key Outcomes Among HIV-Infected Adults in Low- and Middle-Income Countries: A Systematic Review

Background:HIV-infected adults are at increased risk of severe malaria and death. Malaria prevention in people living with HIV (PLHIV) consists of several interventions, including cotrimoxazole (CTX) prophylaxis and insecticide-treated nets (ITNs). We conducted a systematic review of the available evidence. Methods:MEDLINE, EmBase, Global Health, CINAHL, SOCA, and African Index Medicus were used to identify articles relevant to the CTX prophylaxis and ITNs interventions from 1995 to July 2014. For each individual study, we assessed the quality of evidence and the impact of the 2 interventions on the outcomes of mortality, morbidity, retention in care, quality of life, and/or prevention of ongoing HIV transmission. For each outcome, we summarized the quality of the overall body of evidence, the expected impact, and costing and cost-effectiveness (CE). Findings:The overall quality of evidence regarding malaria-related morbidity was rated as “good” for CTX prophylaxis and “fair” for ITN use; the expected “impact” of these interventions on morbidity was rated “high” and “uncertain,” respectively. Three studies that addressed the costing and CE of ITN provision for malaria prevention in PLHIV consisted of 2 full “level 1” and 1 partial “level 2” economic evaluations. Conclusions:CTX prophylaxis is effective in reducing malaria-related morbidity among PLHIV. Limited evidence is available with respect to the impact and the CE of ITN use and/or provision in this population.