Estimating Under Five Mortality in Space and Time in a Developing World Context

Accurate estimates of the under-5 mortality rate (U5MR) in a developing world context are a key barometer of the health of a nation. This paper describes new models to analyze survey data on mortality in this context. We are interested in both spatial and temporal description, that is, wishing to estimate U5MR across regions and years, and to investigate the association between the U5MR and spatially-varying covariate surfaces. We illustrate the methodology by producing yearly estimates for subnational areas in Kenya over the period 1980 - 2014 using data from demographic health surveys (DHS). We use a binomial likelihood with fixed effects for the urban/rural stratification to account for the complex survey design. We carry out smoothing using Bayesian hierarchical models with continuous spatial and temporally discrete components. A key component of the model is an offset to adjust for bias due to the effects of HIV epidemics. Substantively, there has been a sharp decline in U5MR in the period 1980 - 2014, but large variability in estimated subnational rates remains. A priority for future research is understanding this variability. Temperature, precipitation and a measure of malaria infection prevalence were candidates for inclusion in the covariate model.Comment: 36 pages, 11 figure

A Bayesian approach for inferring the dynamics of partially observed endemic infectious diseases from space-time-genetic data

We describe a statistical framework for reconstructing the sequence of transmission events between observed cases of an endemic infectious disease using genetic, temporal and spatial information. Previous approaches to reconstructing transmission trees have assumed all infections in the study area originated from a single introduction and that a large fraction of cases were observed. There are as yet no approaches appropriate for endemic situations in which a disease is already well established in a host population and in which there may be multiple origins of infection, or that can enumerate unobserved infections missing from the sample. Our proposed framework addresses these shortcomings, enabling reconstruction of partially observed transmission trees and estimating the number of cases missing from the sample. Analyses of simulated datasets show the method to be accurate in identifying direct transmissions, while introductions and transmissions via one or more unsampled intermediate cases could be identified at high to moderate levels of case detection. When applied to partial genome sequences of rabies virus sampled from an endemic region of South Africa, our method reveals several distinct transmission cycles with little contact between them, and direct transmission over long distances suggesting significant anthropogenic influence in the movement of infected dogs

Recent Findings on Phosphorus Digestibility of Feed Ingredients in Broilers

Accurately meeting the dietary P needs of broilers is critical to ensure optimal bird performance, health, and welfare without causing undue environmental burdens associated with excess dietary P excretion. Phosphorus is commonly supplied in broiler diets from inorganic phosphates derived from non-renewable sources, but it has been estimated that peak P production will occur between 2030-2040 and that the global supply of P could be depleted within this century (Cordell and Drangert, 2009; Nest and Cordell, 2012). To address these concerns, inorganic P use in agriculture, including use in broiler diet formulation, requires careful stewardship. To this end, the dietary inclusion of animal protein meals can help reduce or eliminate the need for inorganic phosphate use, especially when paired with phytase (van Harn et al., 2017). However, the proportion of P available to the bird within commonly used inorganic phosphate and animal protein sources is often not well-defined.With increasing adoption of ileal digestibility of P in feed formulation, additional data are needed to develop robust databases for commonly used and important sources of P. Therefore, the aim of this study was to generate values of AID and SID of P for different inorganic phosphates and meat and bone meal sources using the direct method. In addition, relative P digestibility of these sources was determined using monosodium phosphate as the reference ingredient to provide a basis for comparing quantitative digestibility results with relative values

Modelling wound area in studies of wound healing interventions

BackgroundExperimental studies of wound healing often use survival analysis and time to event outcomes or differences in wound area at a specific time point. However, these methods do not use a potentially large number of observations made over the course of a trial and may be inefficient. A model-based approach can leverage all trial data, but there is little guidance on appropriate models and functional forms to describe wound healing.MethodsWe derive a general statistical model and review a wide range of plausible mathematical models to describe wound healing. We identify a range of possible derived estimands and their derivation from the models. Using data from a trial of an intervention to promote ulcer healing in patients affected by leprosy that included three measurement methods repeated across the course of the study, we compare the goodness-of-fit of the models using a range of methods and estimate treatment effects and healing rate functions with the best-fitting models.ResultsOverall, we included 5,581 ulcer measurements of 1,578 unique images from 130 patients. We examined the performance of a range of models. The square root, log square root, and log quadratic models were the best fitting models across all outcome measurement methods. The estimated treatment effects magnitude and sign varied by time post-randomisation, model type, and outcome type, but across all models there was little evidence of effectiveness. The estimated effects were significantly more precise than non-parametric alternatives. For example, estimated differences from the three outcome measurements at 42-days post-randomisation were − 0.01 cm2 (-0.77, 0.74), -0.44 cm2 (-1.64, 0.76), and 0.11 cm2 (-0.87, 1.08) using a non-parametric method versus − 0.03 cm2 (-0.14, 0.06), 0.06 cm2 (-0.05, 0.17), and 0.03 cm2 (-0.07, 0.17) using a square-root model.ConclusionsModel-based analyses can dramatically improve the precision of estimates but care must be taken to carefully compare and select the best fitting models. The (log) square-root model is strongly recommended reflecting advice from a century ago

Global Reef Expedition: Cook Islands Final Report

The Khaled bin Sultan Living Oceans Foundation embarked on the Global Reef Expedition—the largest coral reef survey and mapping expedition in history—to study the coral reef crisis on a global scale. As part of the 5-year expedition, an international team of scientists traveled to the Cook Islands in 2013 to assess the health and resiliency of their coral reefs. The Global Reef Expedition: Cook Islands Final Report provides a comprehensive summary of the Foundation's research findings from the Cook Islands research mission, along with recommendations for preserving these reefs for the use and enjoyment of future generations.This report provides scientists, managers, and stakeholders with information on the status of corals and reef fish in the Cook Islands and helps further our understanding of the resiliency of these fragile marine ecosystems. Coral reefs face many threats, including pollution, climate change, overfishing, storm damage, and outbreaks of crown-of-thorns starfish. In order to see how these threats impacted reefs, KSLOF worked closely with local leaders, government officials, and members of the Cook Islands Marine Park Steering Committee to study the reefs. Together, they completed over 400 surveys of the coral and reef fish communities surrounding Rarotonga, Aitutaki, and Palmerston Atoll, and collected information to create over 400 km2 of high-resolution habitat and bathymetric maps of the seafloor.

Orientation and verbal fluency in the English Longitudinal Study of Ageing: modifiable risk factors for falls?

Objectives:To determine the relationship between falls and deficits in specific cognitive domains in older adults.Design:An analysis of the English Longitudinal Study of Ageing (ELSA) cohort.Setting:United Kingdom community-based.Participants:5197 community-dwelling older adults recruited to a prospective longitudinal cohort study.Measurements:Data on the occurrence of falls and number of falls, which occurred during a 12-month follow-up period, were assessed against the specific cognitive domains of memory, numeracy skills, and executive function. Binomial logistic regression was performed to evaluate the association between each cognitive domain and the dichotomous outcome of falls in the preceding 12 months using unadjusted and adjusted models.Results:Of the 5197 participants included in the analysis, 1308 (25%) reported a fall in the preceding 12 months. There was no significant association between the occurrence of a fall and specific forms of cognitive dysfunction after adjusting for self-reported hearing, self-reported eyesight, and functional performance. After adjustment, only orientation (odds ratio [OR]: 0.80; 95% confidence intervals [CI]: 0.65-0.98, p = 0.03) and verbal fluency (adjusted OR: 0.98; 95% CI: 0.96-1.00; p = 0.05) remained significant for predicting recurrent falls.Conclusions:The cognitive phenotype rather than cognitive impairment per se may predict future falls in those presenting with more than one fall

Evaluation of the accuracy of bacterial genome reconstruction with Oxford Nanopore R10.4.1 long-read-only sequencing

Whole genome reconstruction of bacterial pathogens has become an important tool for tracking transmission and antimicrobial resistance gene spread, but highly accurate and complete assemblies have largely only historically been achievable using hybrid long and short-read sequencing. We previously found the Oxford Nanopore Technologies (ONT) R10.4/kit12 flowcell/chemistry produced improved assemblies over the R9.4.1/kit10 combination, however long-read only assemblies contained more errors compared to Illumina-ONT hybrid assemblies. ONT have since released an R10.4.1/kit14 flowcell/chemistry upgrade and recommended the use of Bovine Serum Albumin (BSA) during library preparation, both of which reportedly increase accuracy and yield. They have also released updated basecallers trained using native bacterial DNA containing methylation sites intended to fix systematic basecalling errors, including common adenosine (A) to guanine (G) and cytosine (C) to thymine (T) substitutions. To evaluate these improvements, we successfully sequenced four bacterial reference strains, namely Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus, and nine genetically diverse E. coli bloodstream infection-associated isolates from different phylogroups and sequence types, both with and without BSA. These sequences were de novo assembled and compared against Illumina-corrected reference genomes. In this small evaluation of 13 isolates we found that nanopore long read-only R10.4.1/kit 14 assemblies with updated basecallers trained using bacterial methylated DNA produce accurate assemblies with ≥40x depth, sufficient to be cost-effective compared with hybrid ONT/Illumina sequencing in our setting

A social justice perspective on access to human rabies vaccines

Rabies kills tens of thousands of people every year despite being entirely vaccine preventable. Key global health actors have launched a country-driven plan to achieve zero human deaths from dog-mediated rabies by 2030 worldwide. This partnership has recently been strengthened by Gavi, the Vaccine Alliance’s decision to invest in human rabies vaccines for post-exposure prophylaxis (PEP). While nation states are key to rabies elimination, the importance of Gavi's role cannot be understated. Unlike any other actor, Gavi can directly address an otherwise intractable market failure in the inadequate supply of rabies PEP. In this commentary, we employ the Capabilities Approach to identify the barriers to PEP access that lead to this market failure and, as a result, unnecessary deaths and suffering. We show the role that Gavi can play in reducing exposure of PEP supply to market forces as a matter of social justice, and hence redress the inequity underlying human rabies deaths

Impaired response inhibition and excess cortical thickness as candidate endophenotypes for trichotillomania.

This is the author accepted manuscript. the final version is available via Elsevier at http://www.sciencedirect.com/science/article/pii/S0022395614002465.Trichotillomania is characterized by repetitive pulling out of one's own hair. Impaired response inhibition has been identified in patients with trichotillomania, along with gray matter density changes in distributed neural regions including frontal cortex. The objective of this study was to evaluate impaired response inhibition and abnormal cortical morphology as candidate endophenotypes for the disorder. Subjects with trichotillomania (N = 12), unaffected first-degree relatives of these patients (N = 10), and healthy controls (N = 14), completed the Stop Signal Task (SST), a measure of response inhibition, and structural magnetic resonance imaging scans. Group differences in SST performance and cortical thickness were explored using permutation testing. Groups differed significantly in response inhibition, with patients demonstrating impaired performance versus controls, and relatives occupying an intermediate position. Permutation cluster analysis revealed significant excesses of cortical thickness in patients and their relatives compared to controls, in right inferior/middle frontal gyri (Brodmann Area, BA 47 & 11), right lingual gyrus (BA 18), left superior temporal cortex (BA 21), and left precuneus (BA 7). No significant differences emerged between groups for striatum or cerebellar volumes. Impaired response inhibition and an excess of cortical thickness in neural regions germane to inhibitory control, and action monitoring, represent vulnerability markers for trichotillomania. Future work should explore genetic and environmental associations with these biological markers.This research was supported by a grant from the Trichotillomania Learning Center, USA, to Mr. Odlaug; and by a grant from the Academy of Medical Sciences, UK, to Dr. Chamberlain. Neither of these entities had any further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication

MARVEL Analysis of the Measured High-Resolution Rovibronic Spectra of 90Zr16O

Zirconium oxide(ZrO) is an important astrophysical molecule that defines the S-star classification class for cool giant stars. Accurate, empirical rovibronic energy levels, with associated labels and uncertainties, are reported for 9 low-lying electronic states of the diatomic 90Zr16O molecule. These 8088 empirical energy levels are determined using the Marvel (Measured Active Rotational-Vibrational Energy Levels) algorithm with 23 317 input assigned transition frequencies, 22 549 of which were validated. A temperature-dependent partition function is presented alongside updated spectroscopic constants for the 9 low-lying electronic states