Semiparametric Bayesian Density Estimation with Disparate Data Sources: A Meta-Analysis of Global Childhood Undernutrition

Undernutrition, resulting in restricted growth, and quantified here using height-for-age z-scores, is an important contributor to childhood morbidity and mortality. Since all levels of mild, moderate and severe undernutrition are of clinical and public health importance, it is of interest to estimate the shape of the z-scores' distributions. We present a finite normal mixture model that uses data on 4.3 million children to make annual country-specific estimates of these distributions for under-5-year-old children in the world's 141 low- and middle-income countries between 1985 and 2011. We incorporate both individual-level data when available, as well as aggregated summary statistics from studies whose individual-level data could not be obtained. We place a hierarchical Bayesian probit stick-breaking model on the mixture weights. The model allows for nonlinear changes in time, and it borrows strength in time, in covariates, and within and across regional country clusters to make estimates where data are uncertain, sparse, or missing. This work addresses three important problems that often arise in the fields of public health surveillance and global health monitoring. First, data are always incomplete. Second, different data sources commonly use different reporting metrics. Last, distributions, and especially their tails, are often of substantive interest.Comment: 41 total pages, 6 figures, 1 tabl

Children’s height and weight in rural and urban populations in low-income and middle-income countries: a systematic analysis of population-representative data

Background Urban living aff ects children’s nutrition and growth, which are determinants of their survival, cognitive development, and lifelong health. Little is known about urban–rural diff erences in children’s height and weight, and how these diff erences have changed over time. We aimed to investigate trends in children’s height and weight in rural and urban settings in low-income and middle-income countries, and to assess changes in the urban–rural diff erentials in height and weight over time. Methods We used comprehensive population-based data and a Bayesian hierarchical mixture model to estimate trends in children’s height-for-age and weight-for-age Z scores by rural and urban place of residence, and changes in urban–rural diff erentials in height and weight Z scores, for 141 low-income and middle-income countries between 1985 and 2011. We also estimated the contribution of changes in rural and urban height and weight, and that of urbanisation, to the regional trends in these outcomes. Findings Urban children are taller and heavier than their rural counterparts in almost all low-income and middleincome countries. The urban–rural diff erential is largest in Andean and central Latin America (eg, Peru, Honduras, Bolivia, and Guatemala); in some African countries such as Niger, Burundi, and Burkina Faso; and in Vietnam and China. It is smallest in southern and tropical Latin America (eg, Chile and Brazil). Urban children in China, Chile, and Jamaica are the tallest in low-income and middle-income countries, and children in rural areas of Burundi, Guatemala, and Niger the shortest, with the tallest and shortest more than 10 cm apart at age 5 years. The heaviest children live in cities in Georgia, Chile, and China, and the most underweight in rural areas of Timor-Leste, India, Niger, and Bangladesh. Between 1985 and 2011, the urban advantage in height fell in southern and tropical Latin America and south Asia, but changed little or not at all in most other regions. The urban–rural weight diff erential also decreased in southern and tropical Latin America, but increased in east and southeast Asia and worldwide, because weight gain of urban children outpaced that of rural children.Interpretation Further improvement of child nutrition will require improved access to a stable and aff ordable food supply and health care for both rural and urban children, and closing of the the urban–rural gap in nutritional status

Global marine bacterial diversity peaks at high latitudes in winter.

Genomic approaches to characterizing bacterial communities are revealing significant differences in diversity and composition between environments. But bacterial distributions have not been mapped at a global scale. Although current community surveys are way too sparse to map global diversity patterns directly, there is now sufficient data to fit accurate models of how bacterial distributions vary across different environments and to make global scale maps from these models. We apply this approach to map the global distributions of bacteria in marine surface waters. Our spatially and temporally explicit predictions suggest that bacterial diversity peaks in temperate latitudes across the world's oceans. These global peaks are seasonal, occurring 6 months apart in the two hemispheres, in the boreal and austral winters. This pattern is quite different from the tropical, seasonally consistent diversity patterns observed for most macroorganisms. However, like other marine organisms, surface water bacteria are particularly diverse in regions of high human environmental impacts on the oceans. Our maps provide the first picture of bacterial distributions at a global scale and suggest important differences between the diversity patterns of bacteria compared with other organisms

Meta-analysis fine-mapping is often miscalibrated at single-variant resolution

Meta-analysis is pervasively used to combine multiple genome-wide association studies (GWASs). Fine-mapping of meta-analysis studies is typically performed as in a single-cohort study. Here, we first demonstrate that heterogeneity (e.g., of sample size, phenotyping, imputation) hurts calibration of meta-analysis fine-mapping. We propose a summary statistics-based quality-control (QC) method, suspicious loci analysis of meta-analysis summary statistics (SLALOM), that identifies suspicious loci for meta-analysis fine-mapping by detecting outliers in association statistics. We validate SLALOM in simulations and the GWAS Catalog. Applying SLALOM to 14 meta-analyses from the Global Biobank Meta-analysis Initiative (GBMI), we find that 67% of loci show suspicious patterns that call into question fine-mapping accuracy. These predicted suspicious loci are significantly depleted for having nonsynonymous variants as lead variant (2.7×; Fisher's exact p = 7.3 × 10−4). We find limited evidence of fine-mapping improvement in the GBMI meta-analyses compared with individual biobanks. We urge extreme caution when interpreting fine-mapping results from meta-analysis of heterogeneous cohorts.</p

Targeted delivery of anti-inflammatory therapy to rheumatoid tissue by fusion proteins containing an IL-4-linked synovial targeting peptide

We provide first-time evidence that the synovial endothelium-targeting peptide (SyETP) CKSTHDRLC successfully delivers conjugated IL-4 to human rheumatoid synovium transplanted into SCID mice. SyETP, previously isolated by in vivo phage display and shown to preferentially localize to synovial xenografts, was linked by recombinant technology to hIL-4 via an MMP-cleavable sequence. Both IL-4 and the MMP-cleavable sequence were shown to be functional. IL-4-SyETP augmented production of IL-1ra by synoviocytes stimulated with IL-1[beta] in a dose-dependent manner. In vivo imaging confirmed increased retention of SyETP-linked-IL-4 in synovial grafts which was enhanced by increasing number of copies (one to three) in the constructs. Strikingly, SyETP delivered bioactive IL-4 in vivo as demonstrated by increased pSTAT6 in synovial grafts. Thus, this study provides proof of concept for peptide-tissue-specific targeted immunotherapy in rheumatoid arthritis. This technology is potentially applicable to other biological therapies providing enhanced potency to inflammatory sites and reducing systemic toxicity

Validation of the historical adulthood physical activity questionnaire (HAPAQ) against objective measurements of physical activity.

BACKGROUND: Lifetime physical activity energy expenditure (PAEE) is an important determinant of risk for many chronic diseases but remains challenging to measure. Previously reported historical physical activity (PA) questionnaires appear to be reliable, but their validity is less well established. METHODS: We sought to design and validate an historical adulthood PA questionnaire (HAPAQ) against objective PA measurements from the same individuals. We recruited from a population-based cohort in Cambridgeshire, UK, (Medical Research Council Ely Study) in whom PA measurements, using individually calibrated heart rate monitoring, had been obtained in the past, once between 1994 and 1996 and once between 2000 and 2002. 100 individuals from this cohort attended for interview. Historical PA within the domains of home, work, transport, sport and exercise was recalled using the questionnaire by asking closed questions repeated for several discrete time periods from the age of 20 years old to their current age. The average PAEE from the 2 periods of objective measurements was compared to the self-reported data from the corresponding time periods in the questionnaire. RESULTS: Significant correlations were observed between HAPAQ-derived and objectively measured total PAEE for both time periods (Spearman r = 0.44; P < 0.001). Similarly, self-reported time spent in vigorous PA was significantly correlated with objective measurements of vigorous PA (Spearman r = 0.40; P < 0.001). CONCLUSIONS: HAPAQ demonstrates convergent validity for total PAEE and vigorous PA. This instrument will be useful for ranking individuals according to their past PA in studies of chronic disease aetiology, where activity may be an important underlying factor contributing to disease pathogenesis.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Brief Engagement and Acceptance Coaching for Hospice Settings (the BEACHeS study): Results from a Phase I study of acceptability and initial effectiveness in people with non-curative cancer.

Objectives: Transitioning into palliative care is psychologically demanding for people with advanced cancer, and there is a need for acceptable and effective interventions to support this. We aimed to develop and pilot test a brief Acceptance and Commitment Therapy (ACT) based intervention to improve quality of life and distress. Methods: Our mixed-method design included: (i) quantitative effectiveness testing using Single Case Experimental Design (SCED), (ii) qualitative interviews with participants, and (iii) focus groups with hospice staff. The five-session, in-person intervention was delivered to 10 participants; five completed at least 80%. Results: At baseline, participants reported poor quality of life but low distress. Most experienced substantial physical health deterioration during the study. SCED analysis methods did not show conclusively significant effects, but there was some indication that outcome improvement followed changes in expected intervention processes variables. Quantitative and qualitative data together demonstrates acceptability, perceived effectiveness and safety of the intervention. Qualitative interviews and focus groups were also used to gain feedback on intervention content and to make design recommendations to maximise success of later feasibility trials. Conclusions: This study adds to the growing evidence base for ACT in people with advanced cancer. A number of potential intervention mechanisms, for example a distress-buffering hypothesis, are raised by our data and these should be addressed in future research using randomised controlled trial designs. Our methodological recommendations—including recruiting non-cancer diagnoses, and earlier in the treatment trajectory—likely apply more broadly to the delivery of psychological intervention in the palliative care setting