Caregiver socioemotional health as a determinant of child wellâ being in schoolâ aged and adolescent Ugandan children with and without perinatal HIV exposure

ObjectiveCaregiver socioâ emotional attributes are major determinants of child wellâ being. This investigation in vulnerable schoolâ aged Ugandan children estimates relationships between children’s wellâ being and their caregiver’s anxiety, depression and social support.MethodsPerinatally HIVâ infected, HIVâ exposed uninfected and HIVâ unexposed Ugandan children and their caregivers were enrolled. Perinatal HIV status was determined by 18 months of age using DNAâ polymerase chainâ reaction test; status was confirmed via HIV rapid diagnostic test when children were 6â 18 years old. Five indicators of child wellâ being (distress, hopelessness, positive future orientation, esteem and quality of life (QOL)) and caregiversâ socioemotional status (depressive symptoms, anxiety and social support) were measured using validated, culturally adapted and translated instruments. Categories based on tertiles of each caregiver psychosocial indicator were defined. Linear regression analyses estimated percent differences (β) and corresponding 95% confidence intervals (CI) for child wellâ being in relation to caregiver’s psychosocial status.ResultsAs per tertile increment, caregiver anxiety was associated with 2.7% higher distress (95%CI:0.2%, 5.3%) and lower selfâ esteem/QOL (β = â 1.3%/â 2.6%; 95%CI: â 5.0%,â 0.2%) in their children. Child distress/hopelessness increased (β = 3.3%/7.6%; 95%CI:0.4%, 14.7%) and selfâ esteem/QOL decreased 2.3% (β = â 2.3%/â 4.4%; 95%CI: â 7.2%, â 1.3%) as per tertile increment in caregiver depression. Higher caregiver social support was associated with lower distress and higher positive outlook (β = 3%; 95%CI:1.4%, 4.5%) in their children. HIVâ infected/exposed children had most caregiver depressionâ related QOL deficit (β = â 5.2%/â 6.8%; 95%CI: â 12.4%, â 0.2%) and HIVâ unexposed children had most caregiver social supportâ related enhancements in positive outlook (β=4.5%; 95%CI:1.9%, 7.1%).ConclusionsCaregiver anxiety, depressive symptoms and low social support were associated with worse wellâ being in schoolâ aged and adolescent children. Improvement of caregiver mental health and strengthening caregiver social support systems may be a viable strategy for improving wellâ being of vulnerable children and adolescents in this setting.ObjectifLes attributs socioâ affectifs des responsables d’enfants sont des déterminants majeurs du bienâ être des enfants. Cette investigation menée auprès d’enfants ougandais vulnérables dâ âge scolaire a estimé les relations entre le bienâ être des enfants et l’anxiété, la dépression et le soutien social de leur responsable.MéthodesDes enfants ougandais infectés par le VIH de manière périnatale, exposés au VIH mais non infectés, et non exposés au VIH ainsi que leurs responsables ont été inscrits. Le statut VIH périnatal a été déterminé à lâ âge de 18 mois à l’aide du test de PCR de lâ ADN; le statut a été confirmé par un test de diagnostic rapide du VIH chez les enfants âgés de 6 à 18 ans. Cinq indicateurs du bienâ être de l’enfant (détresse, désespoir, orientation future positive, estime et qualité de vie (QV)), et le statut psychosocial des responsables (symptômes dépressifs, anxiété et soutien social) ont été mesurés à l’aide de méthodes validées, adaptées à la culture et respectées et d’outils traduits. Des catégories basées sur les tertiles de chaque indicateur psychosocial du responsable ont été définies. Des analyses de régression linéaire ont estimé les différences en pourcentage (β) et les intervalles de confiance (IC) à 95% correspondants pour le bienâ être de l’enfant par rapport au statut psychosocial de leurs responsables.RésultatsPar incrément de tertile, l’anxiété des responsables était associé à 2,7% de détresse plus élevé (IC95%: 0,2%, 5,3%) et de faible estime de soi/QV (β = â 1,3%/â 2,6%; IC95%: â 5,0%, â 0,2%) chez leurs enfants. La détresse et le désespoir des enfants augmentaient (β = 3,3%/7,6%; IC95%: 0,4%, 14,7%) et l’estime de soi/QV diminuait de 2,3% (β = â 2,3%/â 4,4%; IC95%: â 7,2%, â 1,3%) par incrément de tertile de la dépression chez le responsable. Un soutien social plus élevé des responsables était associé à une détresse moindre et à une perspective positive plus élevée (β = 3%; IC95%: 1,4%, 4,5%) chez leurs enfants. Les enfants infectés/exposés au VIH présentaient pour la plupart un déficit de QV lié à la dépression de leurs responsables (β = â 5,2%/â 6,8%; IC95%: â 12,4%, â 0,2%), et ceux non exposés au VIH présentaient pour la plupart des améliorations en perspective positive liées au soutien social de leurs responsables (β = 4,5%; IC95%: 1,9%, 7,1%).ConclusionsL’anxiété, les symptômes dépressifs et un faible soutien social du responsable étaient associés à un bienâ être précaire chez les enfants dâ âge scolaire et les adolescents. L’amélioration de la santé mentale des responsables et le renforcement des systèmes de soutien social pour les responsables peuvent constituer une stratégie viable pour améliorer le bienâ être des enfants et des adolescents vulnérables dans cette région.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149358/1/tmi13221.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149358/2/tmi13221_am.pd

Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation.

BackgroundMucopolysaccharidosis I (MPS IH) is a lysosomal storage disease treated with hematopoietic cell transplantation (HCT) because it stabilizes cognitive deterioration, but is insufficient to alleviate all somatic manifestations. Intravenous laronidase improves somatic burden in attenuated MPS I. It is unknown whether laronidase can improve somatic disease following HCT in MPS IH. The objective of this study was to evaluate the effects of laronidase on somatic outcomes of patients with MPS IH previously treated with HCT.MethodsThis 2-year open-label pilot study of laronidase included ten patients (age 5-13 years) who were at least 2 years post-HCT and donor engrafted. Outcomes were assessed semi-annually and compared to historic controls.ResultsThe two youngest participants had a statistically significant improvement in growth compared to controls. Development of persistent high-titer anti-drug antibodies (ADA) was associated with poorer 6-min walk test (6MWT) performance; when patients with high ADA titers were excluded, there was a significant improvement in the 6MWT in the remaining seven patients.ConclusionsLaronidase seemed to improve growth in participants <8 years old, and 6MWT performance in participants without ADA. Given the small number of patients treated in this pilot study, additional study is needed before definitive conclusions can be made

I Spy Transits and Pulsations: Empirical Variability in White Dwarfs Using Gaia and the Zwicky Transient Facility

We present a novel method to detect variable astrophysical objects and transient phenomena using anomalous excess scatter in repeated measurements from public catalogs of Gaia DR2 and Zwicky Transient Facility (ZTF) DR3 photometry. We first provide a generalized, all-sky proxy for variability using only Gaia DR2 photometry, calibrated to white dwarf stars. To ensure more robust candidate detection, we further employ a method combining Gaia with ZTF photometry and alerts. To demonstrate the efficacy, we apply this latter technique to a sample of roughly $12,100$ white dwarfs within 200 pc centered on the ZZ Ceti instability strip, where hydrogen-atmosphere white dwarfs are known to pulsate. Through inspecting the top $1\%$ samples ranked by these methods, we demonstrate that both the Gaia-only and ZTF-informed techniques are highly effective at identifying known and new variable white dwarfs, which we verify using follow-up, high-speed photometry. We confirm variability in all 33 out of 33 ($100\%$) observed white dwarfs within our top $1\%$ highest-ranked candidates, both inside and outside the ZZ Ceti instability strip. In addition to dozens of new pulsating white dwarfs, we also identify five white dwarfs highly likely to show transiting planetary debris; if confirmed, these systems would more than triple the number of white dwarfs known to host transiting debris.Comment: 30 pages, 14 figures, revised and accepted to ApJ on March 11, 202

Phenotypic transition of microglia into astrocyte-like cells associated with disease onset in a model of inherited ALS

Microglia and reactive astrocytes accumulate in the spinal cord of rats expressing the Amyotrophic lateral sclerosis (ALS)-linked SOD1ᴳ⁹³ᴬ mutation. We previously reported that the rapid progression of paralysis in ALS rats is associated with the appearance of prolifer- ative astrocyte-like cells that surround motor neurons. These cells, designated as Aberrant Astrocytes (AbA cells) because of their atypical astrocytic phenotype, exhibit high toxicity to motor neurons. However, the cellular origin of AbA cells remains unknown. Because AbA cells are labeled with the proliferation marker Ki67, we analyzed the phenotypic makers of proliferating glial cells that surround motor neurons by immunohistochemistry. The number of Ki67⁺AbA cells sharply increased in symptomatic rats, displaying large cell bodies with processes embracing motor neurons. Most were co-labeled with astrocytic marker GFAP concurrently with the microglial markers Iba1 and CD163. Cultures of spinal cord prepared from symptomatic SOD1ᴳ⁹³ᴬ rats yielded large numbers of microglia expressing Iba1, CD11b, and CD68. Cells sorted for CD11b expression by flow cytometry transformed into AbA cells within two weeks. During these two weeks, the expression of microglial markers largely disappeared, while GFAP and S100β expression increased. The phenotypic transition to AbA cells was stimulated by forskolin. These findings provide evidence for a subpopulation of proliferating microglial cells in SOD1ᴳ⁹³ᴬ rats that undergo a phenotypic transition into AbA cells after onset of paralysis that may promote the fulminant disease progression. These cells could be a therapeutic target for slowing paralysis progression in ALS

The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software

Stromal gene signatures in large-B-cell lymphomas.

BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear. METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group. RESULTS: A multivariate model created from three gene-expression signatures--termed germinal-center B-cell, stromal-1, and stromal-2 --predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density. CONCLUSIONS: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment

Earlier snowmelt may lead to late season declines in plant productivity and carbon sequestration in Arctic tundra ecosystems

Arctic warming is affecting snow cover and soil hydrology, with consequences for carbon sequestration in tundra ecosystems. The scarcity of observations in the Arctic has limited our understanding of the impact of covarying environmental drivers on the carbon balance of tundra ecosystems. In this study, we address some of these uncertainties through a novel record of 119 site-years of summer data from eddy covariance towers representing dominant tundra vegetation types located on continuous permafrost in the Arctic. Here we found that earlier snowmelt was associated with more tundra net CO2 sequestration and higher gross primary productivity (GPP) only in June and July, but with lower net carbon sequestration and lower GPP in August. Although higher evapotranspiration (ET) can result in soil drying with the progression of the summer, we did not find significantly lower soil moisture with earlier snowmelt, nor evidence that water stress affected GPP in the late growing season. Our results suggest that the expected increased CO2 sequestration arising from Arctic warming and the associated increase in growing season length may not materialize if tundra ecosystems are not able to continue sequestering CO2 later in the season.Peer reviewe

Modeling causes of death: an integrated approach using CODEm

Background: Data on causes of death by age and sex are a critical input into health decision-making. Priority setting in public health should be informed not only by the current magnitude of health problems but by trends in them. However, cause of death data are often not available or are subject to substantial problems of comparability. We propose five general principles for cause of death model development, validation, and reporting.Methods: We detail a specific implementation of these principles that is embodied in an analytical tool - the Cause of Death Ensemble model (CODEm) - which explores a large variety of possible models to estimate trends in causes of death. Possible models are identified using a covariate selection algorithm that yields many plausible combinations of covariates, which are then run through four model classes. The model classes include mixed effects linear models and spatial-temporal Gaussian Process Regression models for cause fractions and death rates. All models for each cause of death are then assessed using out-of-sample predictive validity and combined into an ensemble with optimal out-of-sample predictive performance.Results: Ensemble models for cause of death estimation outperform any single component model in tests of root mean square error, frequency of predicting correct temporal trends, and achieving 95% coverage of the prediction interval. We present detailed results for CODEm applied to maternal mortality and summary results for several other causes of death, including cardiovascular disease and several cancers.Conclusions: CODEm produces better estimates of cause of death trends than previous methods and is less susceptible to bias in model specification. We demonstrate the utility of CODEm for the estimation of several major causes of death

Phylogenetic diversity of Amazonian tree communities

This is the peer reviewed version of the following article: Honorio Coronado, E. N., Dexter, K. G., Pennington, R. T., Chave, J., Lewis, S. L., Alexiades, M. N., Alvarez, E., Alves de Oliveira, A., Amaral, I. L., Araujo-Murakami, A., Arets, E. J. M. M., Aymard, G. A., Baraloto, C., Bonal, D., Brienen, R., Cerón, C., Cornejo Valverde, F., Di Fiore, A., Farfan-Rios, W., Feldpausch, T. R., Higuchi, N., Huamantupa-Chuquimaco, I., Laurance, S. G., Laurance, W. F., López-Gonzalez, G., Marimon, B. S., Marimon-Junior, B. H., Monteagudo Mendoza, A., Neill, D., Palacios Cuenca, W., Peñuela Mora, M. C., Pitman, N. C. A., Prieto, A., Quesada, C. A., Ramirez Angulo, H., Rudas, A., Ruschel, A. R., Salinas Revilla, N., Salomão, R. P., Segalin de Andrade, A., Silman, M. R., Spironello, W., ter Steege, H., Terborgh, J., Toledo, M., Valenzuela Gamarra, L., Vieira, I. C. G., Vilanova Torre, E., Vos, V., Phillips, O. L. (2015), Phylogenetic diversity of Amazonian tree communities. Diversity and Distributions, 21: 1295–1307. doi: 10.1111/ddi.12357, which has been published in final form at 10.1111/ddi.12357Aim: To examine variation in the phylogenetic diversity (PD) of tree communities across geographical and environmental gradients in Amazonia. Location: Two hundred and eighty-three c. 1 ha forest inventory plots from across Amazonia. Methods: We evaluated PD as the total phylogenetic branch length across species in each plot (PDss), the mean pairwise phylogenetic distance between species (MPD), the mean nearest taxon distance (MNTD) and their equivalents standardized for species richness (ses.PDss, ses.MPD, ses.MNTD). We compared PD of tree communities growing (1) on substrates of varying geological age; and (2) in environments with varying ecophysiological barriers to growth and survival. Results: PDss is strongly positively correlated with species richness (SR), whereas MNTD has a negative correlation. Communities on geologically young- and intermediate-aged substrates (western and central Amazonia respectively) have the highest SR, and therefore the highest PDss and the lowest MNTD. We find that the youngest and oldest substrates (the latter on the Brazilian and Guiana Shields) have the highest ses.PDss and ses.MNTD. MPD and ses.MPD are strongly correlated with how evenly taxa are distributed among the three principal angiosperm clades and are both highest in western Amazonia. Meanwhile, seasonally dry tropical forest (SDTF) and forests on white sands have low PD, as evaluated by any metric. Main conclusions: High ses.PDss and ses.MNTD reflect greater lineage diversity in communities. We suggest that high ses.PDss and ses.MNTD in western Amazonia results from its favourable, easy-to-colonize environment, whereas high values in the Brazilian and Guianan Shields may be due to accumulation of lineages over a longer period of time. White-sand forests and SDTF are dominated by close relatives from fewer lineages, perhaps reflecting ecophysiological barriers that are difficult to surmount evolutionarily. Because MPD and ses.MPD do not reflect lineage diversity per se, we suggest that PDss, ses.PDss and ses.MNTD may be the most useful diversity metrics for setting large-scale conservation priorities.FINCyT - PhD studentshipSchool of Geography of the University of LeedsRoyal Botanic Garden EdinburghNatural Environment Research Council (NERC)Gordon and Betty Moore FoundationEuropean Union's Seventh Framework ProgrammeERCCNPq/PELDNSF - Fellowshi

Interobserver reliability of classification and characterization of proximal humeral fractures: a comparison of two and three-dimensional CT

Interobserver reliability for the classification of proximal humeral fractures is limited. The aim of this study was to test the null hypothesis that interobserver reliability of the AO classification of proximal humeral fractures, the preferred treatment, and fracture characteristics is the same for two-dimensional (2-D) and three-dimensional (3-D) computed tomography (CT). Members of the Science of Variation Group--fully trained practicing orthopaedic and trauma surgeons from around the world--were randomized to evaluate radiographs and either 2-D CT or 3-D CT images of fifteen proximal humeral fractures via a web-based survey and respond to the following four questions: (1) Is the greater tuberosity displaced? (2) Is the humeral head split? (3) Is the arterial supply compromised? (4) Is the glenohumeral joint dislocated? They also classified the fracture according to the AO system and indicated their preferred treatment of the fracture (operative or nonoperative). Agreement among observers was assessed with use of the multirater kappa (κ) measure. Interobserver reliability of the AO classification, fracture characteristics, and preferred treatment generally ranged from "slight" to "fair." A few small but statistically significant differences were found. Observers randomized to the 2-D CT group had slightly but significantly better agreement on displacement of the greater tuberosity (κ = 0.35 compared with 0.30, p < 0.001) and on the AO classification (κ = 0.18 compared with 0.17, p = 0.018). A subgroup analysis of the AO classification results revealed that shoulder and elbow surgeons, orthopaedic trauma surgeons, and surgeons in the United States had slightly greater reliability on 2-D CT, whereas surgeons in practice for ten years or less and surgeons from other subspecialties had slightly greater reliability on 3-D CT. Proximal humeral fracture classifications may be helpful conceptually, but they have poor interobserver reliability even when 3-D rather than 2-D CT is utilized. This may contribute to the similarly poor interobserver reliability that was observed for selection of the treatment for proximal humeral fractures. The lack of a reliable classification confounds efforts to compare the outcomes of treatment methods among different clinical trials and reports