Intracluster correlation coefficients and coefficients of variation for perinatal outcomes from five cluster-randomised controlled trials in low and middle-income countries: results and methodological implications

Background: Public health interventions are increasingly evaluated using cluster-randomised trials in which groups rather than individuals are allocated randomly to treatment and control arms. Outcomes for individuals within the same cluster are often more correlated than outcomes for individuals in different clusters. This needs to be taken into account in sample size estimations for planned trials, but most estimates of intracluster correlation for perinatal health outcomes come from hospital-based studies and may therefore not reflect outcomes in the community. In this study we report estimates for perinatal health outcomes from community-based trials to help researchers plan future evaluations.Methods: We estimated the intracluster correlation and the coefficient of variation for a range of outcomes using data from five community-based cluster randomised controlled trials in three low-income countries: India, Bangladesh and Malawi. We also performed a simulation exercise to investigate the impact of cluster size and number of clusters on the reliability of estimates of the coefficient of variation for rare outcomes.Results: Estimates of intracluster correlation for mortality outcomes were lower than those for process outcomes, with narrower confidence intervals throughout for trials with larger numbers of clusters. Estimates of intracluster correlation for maternal mortality were particularly variable with large confidence intervals. Stratified randomisation had the effect of reducing estimates of intracluster correlation. The simulation exercise showed that estimates of intracluster correlation are much less reliable for rare outcomes such as maternal mortality. The size of the cluster had a greater impact than the number of clusters on the reliability of estimates for rare outcomes.Conclusions: The breadth of intracluster correlation estimates reported here in terms of outcomes and contexts will help researchers plan future community-based public health interventions around maternal and newborn health. Our study confirms previous work finding that estimates of intracluster correlation are associated with the prevalence of the outcome of interest, the nature of the outcome of interest ( mortality or behavioural) and the size and number of clusters. Estimates of intracluster correlation for maternal mortality need to be treated with caution and a range of estimates should be used in planning future trials

The effect of participatory women's groups on birth outcomes in Bangladesh: does coverage matter? Study protocol for a randomized controlled trial

Background: Progress on neonatal survival has been slow in most countries. While there is evidence on what works to reduce newborn mortality, there is limited knowledge on how to deliver interventions effectively when health systems are weak. Cluster randomized trials have shown strong reductions in neonatal mortality using community mobilisation with women's groups in rural Nepal and India. A similar trial in Bangladesh showed no impact. A main hypothesis is that this negative finding is due to the much lower coverage of women's groups in the intervention population in Bangladesh compared to India and Nepal. For evidence-based policy making it is important to examine if women's group coverage is a main determinant of their impact. The study aims to test the effect on newborn and maternal health outcomes of a participatory women's group intervention with a high population coverage of women's groups.Methods: A cluster randomised trial of a participatory women's group intervention will be conducted in 3 districts of rural Bangladesh. As we aim to study a women's group intervention with high population coverage, the same 9 intervention and 9 control unions will be used as in the 2005-2007 trial. These had been randomly allocated using the districts as strata. To increase coverage, 648 new groups were formed in addition to the 162 existing groups that were part of the previous trial. An open cohort of women who are permanent residents in the union in which their delivery or death was identified, is enrolled. Women and their newborns are included after birth, or, if a woman dies during pregnancy, after her death. Excluded are women who are temporary residents in the union in which their birth or death was identified. The primary outcome is neonatal mortality in the last 24 months of the study. A low cost surveillance system will be used to record all birth outcomes and deaths to women of reproductive age in the study population. Data on home care practices and health care use are collected through interviews

The equity impact of community women's groups to reduce neonatal mortality: a meta-analysis of four cluster randomized trials

Background: Socioeconomic inequalities in neonatal mortality are substantial in many developing countries. Little is known about how to address this problem. Trials in Asia and Africa have shown strong impacts on neonatal mortality of a participatory learning and action intervention with women's groups. Whether this intervention also reduces mortality inequalities remains unknown. We describe the equity impact of this women's groups intervention on the neonatal mortality rate (NMR) across socioeconomic strata. Methods: We conducted a meta-analysis of all four participatory women's group interventions that were shown to be highly effective in cluster randomized trials in India, Nepal, Bangladesh and Malawi. We estimated intervention effects on NMR and health behaviours for lower and higher socioeconomic strata using random effects logistic regression analysis. Differences in effect between strata were tested. Results: Analysis of 69120 live births and 2505 neonatal deaths shows that the intervention strongly reduced the NMR in lower (50-63% reduction depending on the measure of socioeconomic position used) and higher (35-44%) socioeconomic strata. The intervention did not show evidence of 'elite-capture': among the most marginalized populations, the NMR in intervention areas was 63% lower [95% confidence interval (CI) 48-74%] than in control areas, compared with 35% (95% CI: 15-50%) lower among the less marginalized in the last trial year ( P -value for difference between most/less marginalized: 0.009). The intervention strongly improved home care practices, with no systematic socioeconomic differences in effect. Conclusions: Participatory women's groups with high population coverage benefit the survival chances of newborns from all socioeconomic strata, and perhaps especially those born into the most deprived households

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

Role of Organic Cation Transporter 1, OCT1 in the Pharmacokinetics and Toxicity of cis-Diammine(pyridine)chloroplatinum(II) and Oxaliplatin in Mice

PurposeThe goal of this study was to test the hypothesis that by controlling intracellular uptake, organic cation transporter 1, Oct1 is a key determinant of the disposition and toxicity of cis-diammine(pyridine)chloroplatinum(II)(CDPCP) and oxaliplatin.MethodsPharmacokinetics, tissue accumulation and toxicity of CDPCP and oxaliplatin were compared between Oct1-/- and wild-type mice.ResultsAfter intravenous administration, hepatic and intestinal accumulation of CDPCP was 2.7-fold and 3.9-fold greater in Oct1 wild-type mice (p < 0.001). Deletion of Oct1 resulted in a significantly decreased clearance (0.444 ± 0.0391 ml/min*kg versus 0.649 ± 0.0807 ml/min*kg in wild-type mice, p < 0.05) and volume distribution (1.90 ± 0.161 L/kg versus 3.37 ± 0.196 L/kg in wild-type mice, p < 0.001). Moreover, Oct1 deletion resulted in more severe off-target toxicities in CDPCP-treated mice. Histologic examination of the liver and measurements of liver function indicated that the level of hepatic toxicity was mild and reversible, but was more apparent in the wild-type mice. In contrast, the effect of Oct1 on the pharmacokinetics and toxicity of oxaliplatin in the mice was minimal.ConclusionsOur study suggests that Oct1 plays an important role in the pharmacokinetics, tissue distribution and toxicity of CDPCP, but not oxaliplatin

Anomalous Diffusion Induced by Cristae Geometry in the Inner Mitochondrial Membrane

Diffusion of inner membrane proteins is a prerequisite for correct functionality of mitochondria. The complicated structure of tubular, vesicular or flat cristae and their small connections to the inner boundary membrane impose constraints on the mobility of proteins making their diffusion a very complicated process. Therefore we investigate the molecular transport along the main mitochondrial axis using highly accurate computational methods. Diffusion is modeled on a curvilinear surface reproducing the shape of mitochondrial inner membrane (IM). Monte Carlo simulations are carried out for topologies resembling both tubular and lamellar cristae, for a range of physiologically viable crista sizes and densities. Geometrical confinement induces up to several-fold reduction in apparent mobility. IM surface curvature per se generates transient anomalous diffusion (TAD), while finite and stable values of projected diffusion coefficients are recovered in a quasi-normal regime for short- and long-time limits. In both these cases, a simple area-scaling law is found sufficient to explain limiting diffusion coefficients for permeable cristae junctions, while asymmetric reduction of the junction permeability leads to strong but predictable variations in molecular motion rate. A geometry-based model is given as an illustration for the time-dependence of diffusivity when IM has tubular topology. Implications for experimental observations of diffusion along mitochondria using methods of optical microscopy are drawn out: a non-homogenous power law is proposed as a suitable approach to TAD. The data demonstrate that if not taken into account appropriately, geometrical effects lead to significant misinterpretation of molecular mobility measurements in cellular curvilinear membranes