Association of Care Environment With HIV Incidence and Death Among Orphaned, Separated, and Street-Connected Children and Adolescents in Western Kenya

Importance: In 2015, there were nearly 140 million orphaned children globally, particularly in low- and middle-income regions, and millions more for whom the street is central to their everyday lives. A total of 16.6 million children were orphaned because of deaths associated with HIV/AIDS, of whom 90% live in sub-Saharan Africa. Although most orphaned and separated children and adolescents in this region are cared for by extended family, the large number of children requiring care has produced a proliferation of institutional care. Few studies have investigated the association between care environment and physical health among orphaned and separated youths in sub-Saharan Africa. Objective: To examine the association of care environment with incident HIV and death among orphaned and separated children and adolescents who were living in charitable children’s institutions, family-based settings, and street settings in western Kenya over almost 10 years. Design, Setting, and Participants: The Orphaned and Separated Children’s Assessments Related to Their Health and Well-Being (OSCAR) project was an observational prospective cohort study conducted in Uasin Gishu County, Kenya. The cohort comprised 2551 orphaned, separated, and street-connected children from communities within 8 administrative locations, which included 300 randomly selected households (family-based settings) caring for children who were orphaned from all causes, 19 charitable children’s institutions (institutional settings), and a convenience sample of 100 children who were practicing self-care on the streets (street settings). Participants were enrolled from May 31, 2010, to April 24, 2013, and were followed up until November 30, 2019. Exposures: Care environment (family-based, institutional, or street setting). Main Outcomes and Measures: Survival regression models were used to investigate the association between care environment and incident HIV, death, and time to incident HIV or death. Results: Among 2551 participants, 1230 youths were living in family-based settings, 1230 were living in institutional settings, and 91 were living in street settings. Overall, 1321 participants (51.8%) were male, with a mean (SD) age at baseline of 10.4 (4.8) years. Most participants who were living in institutional (1047 of 1230 youths [85.1%]) or street (71 of 91 youths [78.0%]) settings were double orphaned (ie, both parents had died). A total of 59 participants acquired HIV infection or died during the study period. After adjusting for sex, age, and baseline HIV status, living in a charitable children’s institution was not associated with death (adjusted hazard ratio [AHR], 0.26; 95% CI, 0.07-1.02) or incident HIV (AHR, 1.49; 95% CI, 0.46-4.83). Compared with living in a family-based setting, living in a street setting was associated with death (AHR, 5.46; 95% CI, 2.30-12.94), incident HIV (AHR, 17.31; 95% CI, 5.85-51.25), and time to incident HIV or death (AHR, 7.82; 95% CI, 3.48-17.55). Conclusions and Relevance: In this study, after adjusting for potential confounders, no association was found between care environment and HIV incidence or death among youths living in institutional vs family-based settings. However, living in a street setting vs a family-based setting was associated with both HIV incidence and death. This study’s findings suggest that strengthening of child protection systems and greater investment in evidence-based family support systems that improve child and adolescent health and prevent youth migration to the street are needed for safe and beneficial deinstitutionalization to be implemented at scale

How fast is fast? Eco-evolutionary dynamics and rates of change in populations and phenotypes

It is increasingly recognized that evolution may occur in ecological time. It is not clear, however, how fast evolution – or phenotypic change more generally – may be in comparison with the associated ecology, or whether systems with fast ecological dynamics generally have relatively fast rates of phenotypic change. We developed a new dataset on standardized rates of change in population size and phenotypic traits for a wide range of species and taxonomic groups. We show that rates of change in phenotypes are generally no more than 2/3, and on average about 1/4, the concurrent rates of change in population size. There was no relationship between rates of population change and rates of phenotypic change across systems. We also found that the variance of both phenotypic and ecological rates increased with the mean across studies following a power law with an exponent of two, while temporal variation in phenotypic rates was lower than in ecological rates. Our results are consistent with the view that ecology and evolution may occur at similar time scales, but clarify that only rarely do populations change as fast in traits as they do in abundance

How fast is fast? Eco-evolutionary dynamics and rates of change in populations and phenotypes

It is increasingly recognized that evolution may occur in ecological time. It is not clear, however, how fast evolution – or phenotypic change more generally – may be in comparison with the associated ecology, or whether systems with fast ecological dynamics generally have relatively fast rates of phenotypic change. We developed a new dataset on standardized rates of change in population size and phenotypic traits for a wide range of species and taxonomic groups. We show that rates of change in phenotypes are generally no more than 2/3, and on average about 1/4, the concurrent rates of change in population size. There was no relationship between rates of population change and rates of phenotypic change across systems. We also found that the variance of both phenotypic and ecological rates increased with the mean across studies following a power law with an exponent of two, while temporal variation in phenotypic rates was lower than in ecological rates. Our results are consistent with the view that ecology and evolution may occur at similar time scales, but clarify that only rarely do populations change as fast in traits as they do in abundance

Analyzing high resolution topography for advancing the understanding of mass and energy transfer through landscapes: A review

International audienceThe study of mass and energy transfer across landscapes has recently evolved to comprehensive considerations acknowledging the role of biota and humans as geomorphic agents, as well as the importance of small-scale landscape features. A contributing and supporting factor to this evolution is the emergence over the last two decades of technologies able to acquire high resolution topography (HRT) (meter and sub-meter resolution) data. Landscape features can now be captured at an appropriately fine spatial resolution at which surface processes operate; this has revolutionized the way we study Earth-surface processes. The wealth of information contained in HRT also presents considerable challenges. For example, selection of the most appropriate type of HRT data for a given application is not trivial. No definitive approach exists for identifying and filtering erroneous or unwanted data, yet inappropriate filtering can create artifacts or eliminate/distort critical features. Estimates of errors and uncertainty are often poorly defined and typically fail to represent the spatial heterogeneity of the dataset, which may introduce bias or error for many analyses. For ease of use, gridded products are typically preferred rather than the more information-rich point cloud representations. Thus many users take advantage of only a fraction of the available data, which has furthermore been subjected to a series of operations often not known or investigated by the user. Lastly, standard HRT analysis work-flows are yet to be established for many popular HRT operations, which has contributed to the limited use of point cloud data.In this review, we identify key research questions relevant to the Earth-surface processes community within the theme of mass and energy transfer across landscapes and offer guidance on how to identify the most appropriate topographic data type for the analysis of interest. We describe the operations commonly performed from raw data to raster products and we identify key considerations and suggest appropriate work-flows for each, pointing to useful resources and available tools. Future research directions should stimulate further development of tools that take advantage of the wealth of information contained in the HRT data and address the present and upcoming research needs such as the ability to filter out unwanted data, compute spatially variable estimates of uncertainty and perform multi-scale analyses. While we focus primarily on HRT applications for mass and energy transfer, we envision this review to be relevant beyond the Earth-surface processes community for a much broader range of applications involving the analysis of HRT

Optimizing linkage and retention to hypertension care in rural Kenya (LARK hypertension study): study protocol for a randomized controlled trial

BACKGROUND: Hypertension is the leading global risk factor for mortality. Hypertension treatment and control rates are low worldwide, and delays in seeking care are associated with increased mortality. Thus, a critical component of hypertension management is to optimize linkage and retention to care. METHODS/DESIGN: This study investigates whether community health workers, equipped with a tailored behavioral communication strategy and smartphone technology, can increase linkage and retention of hypertensive individuals to a hypertension care program and significantly reduce blood pressure among them. The study will be conducted in the Kosirai and Turbo Divisions of western Kenya. An initial phase of qualitative inquiry will assess facilitators and barriers of linkage and retention to care using a modified Health Belief Model as a conceptual framework. Subsequently, we will conduct a cluster randomized controlled trial with three arms: 1) usual care (community health workers with the standard level of hypertension care training); 2) community health workers with an additional tailored behavioral communication strategy; and 3) community health workers with a tailored behavioral communication strategy who are also equipped with smartphone technology. The co-primary outcome measures are: 1) linkage to hypertension care, and 2) one-year change in systolic blood pressure among hypertensive individuals. Cost-effectiveness analysis will be conducted in terms of costs per unit decrease in blood pressure and costs per disability-adjusted life year gained. DISCUSSION: This study will provide evidence regarding the effectiveness and cost-effectiveness of strategies to optimize linkage and retention to hypertension care that can be applicable to non-communicable disease management in low- and middle-income countries. TRIAL REGISTRATION: This trial is registered with (NCT01844596) on 30 April 2013

Joint Inference in Weakly-Annotated Image Datasets via Dense Correspondence

We present a principled framework for inferring pixel labels in weakly-annotated image datasets. Most previous, example-based approaches to computer vision rely on a large corpus of densely labeled images. However, for large, modern image datasets, such labels are expensive to obtain and are often unavailable. We establish a large-scale graphical model spanning all labeled and unlabeled images, then solve it to infer pixel labels jointly for all images in the dataset while enforcing consistent annotations over similar visual patterns. This model requires significantly less labeled data and assists in resolving ambiguities by propagating inferred annotations from images with stronger local visual evidences to images with weaker local evidences. We apply our proposed framework to two computer vision problems, namely image annotation with semantic segmentation, and object discovery and co-segmentation (segmenting multiple images containing a common object). Extensive numerical evaluations and comparisons show that our method consistently outperforms the state-of-the-art in automatic annotation and semantic labeling, while requiring significantly less labeled data. In contrast to previous co-segmentation techniques, our method manages to discover and segment objects well even in the presence of substantial amounts of noise images (images not containing the common object), as typical for datasets collected from Internet search

Improved iodine status is associated with improved mental performance of schoolchildren in Benin.

Background: An adequate iodine supply in utero and shortly after birth is known to be crucial to an individual's physical and mental development. The question of whether iodine supplementation later in life can exert a favorable influence on the mental performance of iodine-deficient populations was addressed in various studies, but with contradictory results. Objective: The aim of this study was to examine the effect of an improvement in iodine status on mental and psychomotor performance of schoolchildren (7-11 y) who were moderately to severely iodine deficient. Design: The study, which was originally planned as a double-blind, randomized, placebo-controlled intervention, was carried out in an iodine-deficient population of schoolchildren (n = 196) in northern Benin. As the population began to have access to iodized salt during the 1-y intervention period, the study population was split post hoc - on the basis of urinary iodine concentrations - into a group with improved iodine status and a group with unchanged iodine status. Changes in mental and psychomotor performance over the intervention period were compared. Results: Children with increased urinary iodine concentrations had a significantly greater increase in performance on the combination of mental tests than did the group with no change in urinary iodine concentrations. Conclusions: An improvement in iodine status, rather than iodine status itself, determined mental performance in this population, which was initially iodine deficient. These findings suggest a 'catch-up' effect in terms of mental performance

Protein Phosphatase 2A Controls Ethylene Biosynthesis by Differentially Regulating the Turnover of ACC Synthase Isoforms

The gaseous hormone ethylene is one of the master regulators of development and physiology throughout the plant life cycle. Ethylene biosynthesis is stringently regulated to permit maintenance of low levels during most phases of vegetative growth but to allow for rapid peaks of high production at developmental transitions and under stress conditions. In most tissues ethylene is a negative regulator of cell expansion, thus low basal levels of ethylene biosynthesis in dark-grown seedlings are critical for optimal cell expansion during early seedling development. The committed steps in ethylene biosynthesis are performed by the enzymes 1-aminocyclopropane 1-carboxylate synthase (ACS) and 1-aminocyclopropane 1-carboxylate oxidase (ACO). The abundance of different ACS enzymes is tightly regulated both by transcriptional control and by post-translational modifications and proteasome-mediated degradation. Here we show that specific ACS isozymes are targets for regulation by protein phosphatase 2A (PP2A) during Arabidopsis thaliana seedling growth and that reduced PP2A function causes increased ACS activity in the roots curl in 1-N-naphthylphthalamic acid 1 (rcn1) mutant. Genetic analysis reveals that ethylene overproduction in PP2A-deficient plants requires ACS2 and ACS6, genes that encode ACS proteins known to be stabilized by phosphorylation, and proteolytic turnover of the ACS6 protein is retarded when PP2A activity is reduced. We find that PP2A and ACS6 proteins associate in seedlings and that RCN1-containing PP2A complexes specifically dephosphorylate a C-terminal ACS6 phosphopeptide. These results suggest that PP2A-dependent destabilization requires RCN1-dependent dephosphorylation of the ACS6 C-terminus. Surprisingly, rcn1 plants exhibit decreased accumulation of the ACS5 protein, suggesting that a regulatory phosphorylation event leads to ACS5 destabilization. Our data provide new insight into the circuitry that ensures dynamic control of ethylene synthesis during plant development, showing that PP2A mediates a finely tuned regulation of overall ethylene production by differentially affecting the stability of specific classes of ACS enzymes

Characterization of biomolecular nanoconjugates by high-throughput delivery and spectroscopic difference

Nanoparticle conjugates have the potential for delivering siRNA, splice-shifting oligomers or nucleic acid vaccines, and can be applicable to anticancer therapeutics. This article compares tripartite conjugates with gold nanoparticles or synthetic methoxypoly(ethylene glycol)-block-polyamidoamine dendrimers

Generation of \u3b2 cell-specific human cytotoxic T cells by lentiviral transduction and their survival in immunodeficient human leucocyte antigen-transgenic mice

Several \u3b2 cell antigens recognized by T cells in the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D) are also T cell targets in the human disease. While numerous antigen-specific therapies prevent diabetes in NOD mice, successful translation of rodent findings to patients has been difficult. A human leucocyte antigen (HLA)-transgenic mouse model incorporating human \u3b2 cell-specific T cells might provide a better platform for evaluating antigen-specific therapies. The ability to study such T cells is limited by their low frequency in peripheral blood and the difficulty in obtaining islet-infiltrating T cells from patients. We have worked to overcome this limitation by using lentiviral transduction to 'reprogram' primary human CD8 T cells to express three T cell receptors (TCRs) specific for a peptide derived from the \u3b2 cell antigen islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP265-273 ) and recognized in the context of the human class I major histocompatibility complex (MHC) molecule HLA-A2. The TCRs bound peptide/MHC multimers with a range of avidities, but all bound with at least 10-fold lower avidity than the anti-viral TCR used for comparison. One exhibited antigenic recognition promiscuity. The \u3b2 cell-specific human CD8 T cells generated by lentiviral transduction with one of the TCRs released interferon (IFN)-\u3b3 in response to antigen and exhibited cytotoxic activity against peptide-pulsed target cells. The cells engrafted in HLA-A2-transgenic NOD-scid IL2r\u3b3(null) mice and could be detected in the blood, spleen and pancreas up to 5\u2009weeks post-transfer, suggesting the utility of this approach for the evaluation of T cell-modulatory therapies for T1D and other T cell-mediated autoimmune diseases