Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources. Quantitative views of cellular functions require precise measures of rates of biomolecule production, especially proteins-the direct effectors of biological processes. Here, we present a genome-wide approach, based on ribosome profiling, for measuring absolute protein synthesis rates. The resultant E. coli data set transforms our understanding of the extent to which protein synthesis is precisely controlled to optimize function and efficiency.
A micro-epidemiological analysis of febrile malaria in Coastal Kenya showing hotspots within hotspots. Malaria transmission is spatially heterogeneous. This reduces the efficacy of control strategies, but focusing control strategies on clusters or 'hotspots' of transmission may be highly effective. Among 1500 homesteads in coastal Kenya we calculated (a) the fraction of febrile children with positive malaria smears per homestead, and (b) the mean age of children with malaria per homestead.
Genotypic and Functional Impact of HIV-1 Adaptation to Its Host Population during the North American Epidemic. HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population, we genotypically and functionally compared linked HLA and HIV (Gag/Nef) sequences from 358 historic (1979-1989) and 382 modern (2000-2011) specimens from four key cities in the North American epidemic (New York, Boston, San Francisco, Vancouver).
Early Addition of Topical Corticosteroids in the Treatment of Bacterial Keratitis. Scarring from bacterial keratitis remains a leading cause of visual loss. Our objective is to determine whether topical corticosteroids are beneficial as an adjunctive therapy for bacterial keratitis if given early in the course of infection. The Steroids for Corneal Ulcers Trial (SCUT) was a randomized, double-masked, placebo-controlled trial that overall found no effect of adding topical corticosteroids to topical moxifloxacin hydrochloride in bacterial keratitis. Here, we assess the timing of administration of corticosteroids in a subgroup analysis of the SCUT. We define earlier administration of corticosteroids (vs placebo) as addition after 2 to 3 days of topical antibiotics and later as addition after 4 or more days of topical antibiotics.
Immunoglobulin and T-cell receptor gene high-throughput sequencing quantifies minimal residual disease in acute lymphoblastic leukemia and predicts post-transplant relapse and survival. Minimal residual disease (MRD) quantification is an important predictor of outcome after treatment for acute lymphoblastic leukemia (ALL). Bone marrow ALL burden ≥10-4 after induction predicts subsequent relapse. Likewise, MRD ≥10-4 in bone marrow prior to the initiation of conditioning for allogeneic hematopoietic cell transplantation (allo-HCT) predicts transplant failure. Current methods for MRD quantification in ALL are not sufficiently sensitive for use with peripheral blood specimens and have not been broadly implemented in the management of adults with ALL. Consensus primed immunoglobulin (Ig) and T-cell receptor (TCR) amplification and high-throughput sequencing (HTS) permits use of a standardized algorithm for all patients and can detect leukemia at 10-6 or lower. We applied the Sequenta LymphoSIGHT™ HTS platform to quantification of MRD in 237 samples from 29 adult B-ALL patients before and after allo-HCT.
HIV serostatus and disclosure: implications for infant feeding practice in rural south Nyanza, Kenya. The World Health Organization (WHO) recommends that HIV-infected women practice exclusive breastfeeding (EBF) for the first 6 months postpartum to reduce HIV transmission. The aim of this study was to determine the effects of HIV/AIDS knowledge and other psychosocial factors on EBF practice among pregnant and postpartum women in rural Nyanza, Kenya, an area with a high prevalence of HIV. Data on baseline characteristics and knowledge during pregnancy, as well as infant feeding practices 4-8 weeks after the birth were obtained from 281 pregnant women recruited from nine antenatal clinics. Factors examined included: fear of HIV/AIDS stigma, male partner reactions, lack of disclosure to family members, knowledge of prevention of mother-to-child transmission (PMTCT) and mental health. In the analysis, comparisons were made using chi-squared and t-test methods as well as logistic multivariate regression models.
Strategies for promoting HIV testing uptake: willingness to receive couple-based and collective HIV testing among a cross-sectional online sample of men who have sex with men in China. Low rates of HIV testing drive the rapidly growing HIV epidemic among men who have sex with men (MSM) in China. We examined the potential usefulness of couple-based and collective HIV testing strategies among Chinese MSM. A cross-sectional online survey was conducted among 1113 MSM in 2013. Multivariable logistic regression analyses were conducted to identify factors associated with willingness to receive couple-based and collective testing.
Incidence of TB and HIV in Prospectively Followed Household Contacts of TB Index Patients in South Africa. The objective is to report the incidence rates of TB and HIV in household contacts of index patients diagnosed with TB. Contacts of index TB patients received TB and HIV testing after counseling at their first household visit and were then followed up a year later, in 2010. TB or HIV diagnoses that occurred during the period were determined.
Artemisinin-based Combination Therapies are Efficacious and Safe for Treatment of Uncomplicated Malaria in HIV-infected Ugandan Children. Artemisinin-based combination therapies (ACTs) are highly efficacious and safe but data from HIV-infected children concurrently receiving antiretroviral therapy (ART) and ACTs are limited. We evaluated 28-day outcomes following malaria treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in two cohorts of HIV-infected Ugandan children taking various ART regimens. In one cohort, children under six years of age were randomized to lopinavir/ritonavir (LPV/r) or non-nucleoside reverse transcriptase inhibitors (NNRTI) based ART and treated with AL for uncomplicated malaria. In another cohort, children under 12 months of age were started on nevirapine-based ART if they were eligible, and randomized to AL or DP for the treatment of their first and all subsequent uncomplicated malaria episodes.
Incidence of TB and HIV in Prospectively Followed Household Contacts of TB Index Patients in South Africa. Our objective is to report the incidence rates of TB and HIV in household contacts of index patients diagnosed with TB using a prospective cohort study in the Matlosana sub-district of North West Province, South Africa. Contacts of index TB patients received TB and HIV testing after counseling at their first household visit and were then followed up a year later, in 2010. TB or HIV diagnoses that occurred during the period were determined.
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