No Difference in Growth Outcomes up to 24 Months of Age by Duration of Exposure to Maternal Antiretroviral Therapy Among Children Who Are HIV-Exposed and Uninfected in Malawi

BACKGROUND: With the implementation of lifelong antiretroviral therapy (ART) for HIV treatment and prevention, the proportion of children exposed to ART in utero from conception is increasing. We estimated the effect of timing of ART exposure on growth of children HIV-exposed and uninfected (CHEU) up to Up to 24 months of age in Malawi. METHODS: Data were collected from a prospective cohort of infants HIV-exposed aged 1–6 months (enrollment) and their mothers with HIV enrolled in the National Evaluation of Malawi’s Prevention of Mother-to-Child Transmission of HIV Programme (2014–2018). Anthropometry was measured at enrollment, visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) were calculated using the WHO Growth Standards. Multivariable mixed-effects models with linear splines for age were used to examine differences in growth by timing of ART exposure (from conception, first/second trimester, or third trimester/postpartum). Models were adjusted for confounders selected a priori guided by a conceptual framework. Hypothesized interactions and potential mediators were explored, and interactions with splines were included in final models if P 1.0). CONCLUSION: Reassuringly, ART exposure from conception was not associated with decreased WAZ or LAZ in CHEU Up 24 months of age. Overall growth trajectories suggest CHEU experience growth faltering after 12 months of age and may need support through and beyond the first 2 years of life

Environmental exposure to pyrethroids and sperm sex chromosome disomy: a cross-sectional study

Abstract Background The role of environmental pesticide exposures, such as pyrethroids, and their relationship to sperm abnormalities are not well understood. This study investigated whether environmental exposure to pyrethroids was associated with altered frequency of sperm sex chromosome disomy in adult men. Methods A sample of 75 subjects recruited through a Massachusetts infertility clinic provided urine and semen samples. Individual exposures were measured as urinary concentrations of three pyrethroid metabolites ((3-phenoxybenzoic acid (3PBA), cis- and trans- 3-(2,2-Dichlorovinyl)-1-methylcyclopropane-1,2-dicarboxylic acid (CDCCA and TDCCA)). Multiprobe fluorescence in situ hybridization for chromosomes X, Y, and 18 was used to determine XX, YY, XY, 1818, and total sex chromosome disomy in sperm nuclei. Poisson regression analysis was used to examine the association between aneuploidy rates and pyrethroid metabolites while adjusting for covariates. Results Between 25-56% of the sample were above the limit of detection (LOD) for the pyrethroid metabolites. All sex chromosome disomies were increased by 7-30% when comparing men with CDCCA and TDCCA levels above the LOD to those below the LOD. For 3PBA, compared to those below the LOD, those above the LOD had YY18 disomy rates 1.28 times higher (95% CI: 1.15, 1.42) whereas a reduced rate was seen for XY18 and total disomy (IRR = 0.82; 95% CI: 0.77, 0.87; IRR = 0.93; 95% CI: 0.87-0.97), and no association was seen for XX18 and 1818. Conclusions Our findings suggest that urinary concentrations of CDCCA and TDCCA above the LOD were associated with increased rates of aneuploidy. However the findings for 3BPA were not consistent. This is the first study to examine these relationships, and replication of our findings is needed before the association between pyrethroid metabolites and aneuploidy can be fully defined.http://deepblue.lib.umich.edu/bitstream/2027.42/134538/1/12940_2013_Article_854.pd

Environmental exposure to pyrethroids and sperm sex chromosome disomy: A cross-sectional study

Background The role of environmental pesticide exposures, such as pyrethroids, and their relationship to sperm abnormalities are not well understood. This study investigated whether environmental exposure to pyrethroids was associated with altered frequency of sperm sex chromosome disomy in adult men. Methods A sample of 75 subjects recruited through a Massachusetts infertility clinic provided urine and semen samples. Individual exposures were measured as urinary concentrations of three pyrethroid metabolites ((3-phenoxybenzoic acid (3PBA), cis- and trans- 3-(2,2-Dichlorovinyl)-1-methylcyclopropane-1,2-dicarboxylic acid (CDCCA and TDCCA)). Multiprobe fluorescence in situ hybridization for chromosomes X, Y, and 18 was used to determine XX, YY, XY, 1818, and total sex chromosome disomy in sperm nuclei. Poisson regression analysis was used to examine the association between aneuploidy rates and pyrethroid metabolites while adjusting for covariates. Results Between 25-56% of the sample were above the limit of detection (LOD) for the pyrethroid metabolites. All sex chromosome disomies were increased by 7-30% when comparing men with CDCCA and TDCCA levels above the LOD to those below the LOD. For 3PBA, compared to those below the LOD, those above the LOD had YY18 disomy rates 1.28 times higher (95% CI: 1.15, 1.42) whereas a reduced rate was seen for XY18 and total disomy (IRR = 0.82; 95% CI: 0.77, 0.87; IRR = 0.93; 95% CI: 0.87-0.97), and no association was seen for XX18 and 1818. Conclusions Our findings suggest that urinary concentrations of CDCCA and TDCCA above the LOD were associated with increased rates of aneuploidy. However the findings for 3BPA were not consistent. This is the first study to examine these relationships, and replication of our findings is needed before the association between pyrethroid metabolites and aneuploidy can be fully defined

Risk factors for stunting in children who are HIV-exposed and uninfected after Option B+ implementation in Malawi

Evidence suggests children HIV-exposed and uninfected (CHEU) experience poor growth. We analysed child anthropometrics and explored factors associated with stunting among Malawian CHEU. Mothers with HIV and their infants HIV-exposed were enroled in a nationally representative prospective cohort within the National Evaluation of Malawi's Prevention of Mother-to-Child HIV Transmission Programme after Option B+ implementation (2014-2018). Anthropometry was measured at enrolment (age 1-6 months), visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) z-scores were calculated using World Health Organization Growth Standards; underweight and stunting were defined as WAZ and LAZ more than 2 standard deviations below the reference median. Multivariable logistic regression restricted to CHEU aged 24 months (±3 months) was used to identify factors associated with stunting. Among 1211 CHEU, 562/1211 attended visit 2, of which 529 were aged 24 months (±3 months) and were included. At age 24 months, 40.4% of CHEU were stunted and/or underweight, respectively. In multi-variable analysis, adjusting for child age and sex, the odds of stunting were higher among CHEU with infectious disease diagnosis compared to those with no diagnosis (adjusted odds ratio = 3.35 [95% confidence interval: 1.82-6.17]), which was modified by co-trimoxazole prophylaxis (p = 0.028). Infant low birthweight was associated with an increased odds of stunting; optimal feeding and maternal employment were correlated with reduced odds. This is one of the first studies examining CHEU growth since Option B+. Interventions to improve linear growth among CHEU should address their multi-faceted health risks, alongside maternal ART prescription, and follow-up of mother-child pairs

Large-scale replication study reveals a limit on probabilistic prediction in language comprehension

Do people routinely pre-activate the meaning and even the phonological form of upcoming words? The most acclaimed evidence for phonological prediction comes from a 2005 Nature Neuroscience publication by DeLong, Urbach and Kutas, who observed a graded modulation of electrical brain potentials (N400) to nouns and preceding articles by the probability that people use a word to continue the sentence fragment (‘cloze’). In our direct replication study spanning 9 laboratories (N=334), pre-registered replication-analyses and exploratory Bayes factor analyses successfully replicated the noun-results but, crucially, not the article-results. Pre-registered single-trial analyses also yielded a statistically significant effect for the nouns but not the articles. Exploratory Bayesian single-trial analyses showed that the article-effect may be non-zero but is likely far smaller than originally reported and too small to observe without very large sample sizes. Our results do not support the view that readers routinely pre-activate the phonological form of predictable words.Additional co-authors: Simon Busch-Moreno, Xiao Fu, Jyrki Tuomainen, Eugenia Kulakova, E Matthew Husband, Zdenko Kohút, Shirley-Ann Rueschemeyer, Falk Huetti

Component Processes of Decision Making in a Community Sample of Precariously Housed Persons: Associations With Learning and Memory, and Health-Risk Behaviors

The Iowa Gambling Task (IGT) is a widely used measure of decision making, but its value in signifying behaviors associated with adverse, “real-world” consequences has not been consistently demonstrated in persons who are precariously housed or homeless. Studies evaluating the ecological validity of the IGT have primarily relied on traditional IGT scores. However, computational modeling derives underlying component processes of the IGT, which capture specific facets of decision making that may be more closely related to engagement in behaviors associated with negative consequences. This study employed the Prospect Valence Learning (PVL) model to decompose IGT performance into component processes in 294 precariously housed community residents with substance use disorders. Results revealed a predominant focus on gains and a lack of sensitivity to losses in these vulnerable community residents. Hypothesized associations were not detected between component processes and self-reported health-risk behaviors. These findings provide insight into the processes underlying decision making in a vulnerable substance-using population and highlight the challenge of linking specific decision making processes to “real-world” behaviors

Racemic epinephrine compared to salbutamol in hospitalized young children with bronchiolitis; a randomized controlled clinical trial [ISRCTN46561076]

BACKGROUND: Bronchiolitis is the most common cause of lower respiratory tract illness in infancy, and hospital admission rates appear to be increasing in Canada and the United States. Inhaled beta agonists offer only modest short-term improvement. Trials of racemic epinephrine have shown conflicting results. We sought to determine if administration of racemic epinephrine during hospital stay for bronchiolitis improved respiratory distress, was safe, and shortened length of stay. METHODS: The study was a randomized, double-blind controlled trial of aerosolized racemic epinephrine compared to salbutamol every one to 4 hours in previously well children aged 6 weeks to ≤ 2 years of age hospitalized with bronchiolitis. The primary outcome was symptom improvement as measured by the Respiratory Distress Assessment Instrument (RDAI); secondary outcomes were length of stay in hospital, adverse events, and report of symptoms by structured parental telephone interview one week after discharge. RESULTS: 62 children with a mean age of 6.4 months were enrolled; 80% of children had Respiratory Syncytial Virus (RSV). Racemic epinephrine resulted in significant improvement in wheezing and the total RDAI score on day 2 and over the entire stay (p < 0.05). The mean LOS in the epinephrine arm was 2.6 days (95% CI 2, 3.2) v. 3.4 days in those in the salbutamol group (95% CI 2.6, 4.2) (p > 0.05). Adverse events were not significantly different in the two arms. At one week post-discharge, over half of parents reported that their child still had a respiratory symptom and 40% had less than normal feeding. CONCLUSION: Racemic epinephrine relieves respiratory distress in hospitalized infants with bronchiolitis and is safe but does not abbreviate hospital stay. Morbidity associated with bronchiolitis as identified by parents persists for at least one week after hospital discharge in most infants

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie