Ambulatory and hospitalized childhood pneumonia: a longitudinal study in a peri-urban low-income community with high vaccination coverage in Sub-Saharan Africa

Background Child pneumonia is a substantial cause of childhood mortality and morbidity; it is the largest single cause of under-5 mortality outside the neonatal period. Incidence of child pneumonia, and pneumonia mortality, have decreased substantially due to improved socio-economic attainment, improved HIV programs, coverage of new conjugate vaccines against Streptococcus pneumoniae (PCV) and Haemophilus influenzae type B (Hib), access to early antibiotic therapy, and changing prevalence of pneumonia risk factors. Measurement of community-based pneumonia incidence is difficult; risk factors for pneumonia incidence and factors associated with pneumonia mortality are poorly described in low- and middle-income countries. Careful measurement of pneumonia incidence, and prospective analysis of risk factors is necessary to appreciate the evolving complexities of pneumonia causality and mortality. The aim of this work was to describe the incidence and severity of pneumonia in a birth cohort of children in the first 2 years life; and identify risk factors for pneumonia and for severe outcomes. Methods A prospective birth cohort, the Drakenstein Child Health Study, enrolled mother-infant pairs in two communities outside Cape Town, South Africa. Pregnant women were recruited and followed through pregnancy, labour and delivery, and the first 2 years of the child's life. Comprehensive data collection of risk factors was done through the first 2 years of life. A community pneumonia surveillance system was established; active case finding was used for birth cohort participants over 4 respiratory seasons. Children were examined at scheduled visits and at the time of pneumonia events. Pneumonia or severe pneumonia was diagnosed according to revised World Health Organisation (WHO) guidelines. Chest x-rays were classified according to WHO guidelines. Predictors of ambulatory and hospitalized pneumonia were explored with Poisson regression using generalized estimating equations clustered on mother-infant pairs. Factors associated with death or admission to intensive care unit were analysed with prevalence ratios from modified Poisson regression with robust variance estimation. Findings From March 2012 to March 2015, 1137 pregnant women were enrolled, delivering 1143 live-born infants. Household environmental tobacco smoke exposure was common: 82% of children were exposed in the first 6 months of life. Maternal HIV infection was common: 249 (22%) of 1143 children were HIV-exposed, but only 2 children became HIV-infected. Coverage of primary series of hexavalent vaccine, PCV and Hib was excellent (92%). During the study period (2012 to 2017), there were 795 pneumonia episodes (621 (78%) ambulatory, 274 (22%) hospitalised) in the first 2 years of life. Pneumonia incidence was higher in the first year of life (0.51 episodes per child year (e/cy)) and decreased to 0.25 e/cy in the second year. Active case finding in the birth cohort was more accurate than passive surveillance performed at the community clinics; pneumonia incidence measured by passive surveillance was significantly lower (incidence rate ratio 0.72, 95% CI 0.58 – 0.89) compared to active surveillance. Pneumonia mortality was low: 1.7% of hospitalised cases, and 0.35% of all clinical cases. There was marked variability in pneumonia incidence from year to year during the study. Many risk factors for pneumonia did not have fixed effects, but had different impacts at different ages, and variable effect on ambulatory and hospitalised pneumonia. In multivariable regression, adjusted incidence rate ratios were calculated for 5 risk factors (age< 6 months, male sex, low birth weight (<2500g), maternal smoking, delayed vaccines), which were associated with consistent effects on ambulatory and hospitalised pneumonia. Risk factors for serious outcomes of pneumonia (death or admission to intensive care unit) were identified: age under 2 months, low birth weight and hypoxia. Conclusion In this birth cohort, with low socio-economic status but high vaccination coverage, we demonstrated higher-than expected incidence of pneumonia, but very low mortality, with specific risk factors identified. Active surveillance was important for accurate detection of pneumonia. Children born at low birth weight are at increased risk for pneumonia and for serious outcomes. Pulse oximetry to detect hypoxia, and access to oxygen for children with hypoxic pneumonia, should be included in guidelines. These data will have global applicability for estimation of child pneumonia incidence in regions where direct measurement is impossible. These data can be applied to epidemiology and disease-modelling for child health; they will contribute to long-term morbidity follow-up studies; and they will contribute to understanding the constantly-evolving epidemiology of child pneumonia

Neuron-glial interactions in dendrite growth

Interactions between neurons and glia occupy a central role in many aspects of development, maintenance, and function of the central nervous system (CNS). A fundamental event in CNS development is the elaboration of two distinct neuronal processes, axons and dendrites. The overall aim of this research was to characterize the interactions between central nervous system neurons and astroglial cells that regulate dendrite growth from cerebral cortical neurons. Embryonic (E18) mouse cerebral cortical neurons were cocultured with early postnatal (P4) rat astroglia derived from cerebral cortex, retina, olfactory bulb, mesencephalon, striatum and spinal cord. Axon and dendrite outgrowth from isolated neurons was quantified using morphological and double-labeling immunohistochemical techniques at 18 hours and 1, 3 and 5 days in vitro. Neurons initially extended the same number of neurites, regardless of the source of glial monolayer; however, astroglial cells differed in their ability to maintain primary dendrites. Homotypic cortical astroglia maintained the greatest number of primary dendrites. Astroglia derived from the olfactory bulb and retina maintained intermediate numbers of dendrites, whereas only a small number of primary dendrites were maintained by astroglia derived from striatum, spinal cord or mesencephalon. Initially longer axons were observed from neurons grown on astroglia that did not maintain dendrite number. After 5 days in vitro, axon growth was similar on the various monolayers, total primary dendrite outgrowth, however, was nearly threefold greater on astroglia derived from the cortex, retina and olfactory bulb than on astroglia derived from mesencephalon, striatum or spinal cord. This effect was principally on the number of primary dendrites rather than the elongation of individual dendrites and was independent of neuron survival. Similar morphological differences were observed after 5 days in vitro when cortical neurons were grown on polylysine in either a noncontact coculture system where astroglia continuously conditioned the culture medium or in astroglial conditioned medium. Preliminary biochemical analysis of the medium conditioned by cortical astroglia using heat and trypsin degradation, ultracentrifugation, dialysis, and heparin affinity chromatography suggested that a heparin binding protein with a molecular weight between 10 and 100kDa may be responsible for astroglial mediated dendrite growth. Neurons that were grown in medium conditioned by either mesencephalic or cortical astroglia for the first 24 hours followed by culture medium from astroglia of the alternate source for 4 days in vitro, confirmed that astroglia maintained, rather than initiated, the outgrowth of the primary dendritic arbor. In the next series of experiments, E18 mouse cortical neurons were cocultured with neonatal (P4) or mature (P12) rat astroglia derived from cortex and mesencephalon or astroglia derived from P4 and P12 lesioned cortex. After 5 days in vitro, the maturational age of astroglia did not appear to alter the extent of primary dendrite growth; instead dendrite growth reflected the region of the CNS from which the astroglia were derived. By contrast, a reduced ability to support axon growth from mouse cortical neurons in culture was observed on astroglia derived from mature rat cortex or mesencephalon. Reactive astroglia demonstrated similar neurite supporting characteristics to mature astroglia and were able to maintain dendrite growth, principally primary dendrite number. Axon elongation, however, was reduced on both neonatal and mature reactive astroglia. Neuron survival did not correlate with the ability of the various astroglia to support process outgrowth. Collectively these results indicate: 1) neuron-glial interactions are critical for the regulation of process outgrowth from embryonic cortical neurons in vitro, 2) axon and dendrite growth appear to be differently controlled by astroglia, 3) CNS astroglia demonstrate regional differences in maintaining, but not initiating growth of the primary dendritic arbor, 4) this effect may be due, in part, to release of a diffusible heparin binding protein factor, and 5) mature and reactive astroglia support primary dendrite, but limited axon growth. We propose therefore that the local astroglial environment maintains primary dendrite growth from neurons until synaptic contacts can be established. A mechanism that maintains the primary dendritic arbor and allows separate regulation of axon and dendrite growth, prior to the arrival of afferents, may be critical for establishing appropriate and specific synaptic connections. These findings have important implications in understanding development and function of the mammalian central nervous system and may lead to novel strategies for intervention in acute and chronic neurological disorders

Impact of measles epidemic at Red Cross Children's Hospital, 2009-2010 : a retrospective record review

Includes abstract. Includes bibliographical references

Development Studies Working Paper, no. 52

This report is based on fieldwork which was conducted in 1984. A number of factors, beyond the control of the Development Studies Unit, have delayed the publication of the research findings until now. Though the data may be somewhat dated, the work deals with a much neglected research area, and is published in this Working Paper in the interests of a wider understanding of the nature of the circumstances which characterise the living environments of disadvantaged rural African communities in the Eastern Cape region. As the country enters a period of socio-political transition, rapidly rising social and economic expectations abound. The challenge is to devise appropriate strategies which can be applied in order to initiate a process of development aimed at improving the life-chances and livelihoods of all of the people. In this regard, a strong case can be formulated for some priority to be accorded to marginalised African rural communities.Digitised by Rhodes University Library on behalf of the Institute of Social and Economic Research (ISER

A physically-based parsimonious hydrological model for flash floods in Mediterranean catchments

A spatially distributed hydrological model, dedicated to flood simulation, is developed on the basis of physical process representation (infiltration, overland flow, channel routing). Estimation of model parameters requires data concerning topography, soil properties, vegetation and land use. Four parameters are calibrated for the entire catchment using one flood event. Model sensitivity to individual parameters is assessed using Monte-Carlo simulations. Results of this sensitivity analysis with a criterion based on the Nash efficiency coefficient and the error of peak time and runoff are used to calibrate the model. This procedure is tested on the Gardon d'Anduze catchment, located in the Mediterranean zone of southern France. A first validation is conducted using three flood events with different hydrometeorological characteristics. This sensitivity analysis along with validation tests illustrates the predictive capability of the model and points out the possible improvements on the model's structure and parameterization for flash flood forecasting, especially in ungauged basins. Concerning the model structure, results show that water transfer through the subsurface zone also contributes to the hydrograph response to an extreme event, especially during the recession period. Maps of soil saturation emphasize the impact of rainfall and soil properties variability on these dynamics. Adding a subsurface flow component in the simulation also greatly impacts the spatial distribution of soil saturation and shows the importance of the drainage network. Measures of such distributed variables would help discriminating between different possible model structures

An experimental study on the effect of ambiguity in a coordination game

Article“The final publication is available at Springer via http://dx.doi.org/10.1007/s11238-015-9483-2”."This paper is based on a chapter from Sara le Roux’s PhD thesis.We report an experimental test of the influence of ambiguity on behaviour in a coordination game. We study the behaviour of subjects in the presence of ambiguity and attempt to determine whether they prefer to choose an ambiguity-safe option. We find that this strategy, which is not played in either Nash equilibrium or iterated dominance equilibrium, is indeed chosen quite frequently. This provides evidence that ambiguity-aversion influences behaviour in games. While the behaviour of the Row Player is consistent with randomising between her strategies, the Column Player shows a marked preference for avoiding ambiguity and choosing his ambiguity-safe strategy

Notas sobre la biología del bigete scad, Selar crumenophthalmus (Carangidae), en la isla Reunión, suroeste del océano Índico

The main characteristics of the biology of bigeye scad were studied from commercial fishery catches around Reunion Island. Biometric relationships were calculated. The monitoring of size distribution, aggregated by month, allowed us to estimate the theoretical growth equation using the ELEFAN software. The von Bertalanffy growth parameters were adjusted with a seasonal modulation: L∞ = 265 mm; K = 1.64 year-1; c = 0.068; j = 0.38. The growth of the cohort was quite high during the austral summer (November–April) and decreased during the austral winter (May-October). The arrival of a new cohort with homogeneous small sizes (65 to 90 mm) in the fishery in November coincided with the disappearance of large individuals. A feature of the reproductive biology was that the sex ratio remained constant month by month and that there was no predominance of male or female even in the larger size classes. Fish were mature by April and the proportion of mature fish progressively increased until November, when the gonad-indices were the highest. The size at first maturity (L50) was reached at 215 mm (fork length). The largest specimens observed were 255 mm long (fork length). After reproduction, massive mortality occurred and few individuals survived.Las principales características de la biología del Selar crumenophtalmus fueron estudiadas en la isla Reunión utilizando los desembarques comerciales. Se calcularon las relaciones biométricas. El seguimiento de la distribución mensual de la longitud nos permitió estimar la ecuación de la curva de crecimiento teórico, utilizando el programa ELEFAN. Los parámetros del modelo de crecimiento de Von Bertalanffy fueron ajustados con una modulación estacional: L∞ = 265 mm; K = 1.64 year-1; c = 0.068; j = 0.38. La tasa de crecimiento de las cohortes fue muy rápida durante el verano austral (noviembre-abril) y disminuyó durante el invierno (mayo-octubre). La llegada de una nueva cohorte de pequeños individuos de longitud homogénea (65-90 mm) a la pesquería en noviembre, coincidió con la desaparición de los individuos más grandes. La relación de sexos permaneció constante a lo largo del año y no se vio una superioridad numérica de los machos o de las hembras, ni en las clases de tamaño más grandes. Los primeros peces maduros fueron observados desde el mes de abril y la proporción creció hasta noviembre (índice gonadosomático máximo). La talla de primera madurez (L50) fue alcanzada a los 215 mm (longitud furca, LF). Los peces más grandes observados midieron 255 mm (LF). Después de la reproducción, ocurrió una mortalidad masiva y pocos individuos sobrevivieron

Convergence and Trade-Offs in Riemannian Gradient Descent and Riemannian Proximal Point

In this work, we analyze two of the most fundamental algorithms in geodesically convex optimization: Riemannian gradient descent and (possibly inexact) Riemannian proximal point. We quantify their rates of convergence and produce different variants with several trade-offs. Crucially, we show the iterates naturally stay in a ball around an optimizer, of radius depending on the initial distance and, in some cases, on the curvature. In contrast, except for limited cases, previous works bounded the maximum distance between iterates and an optimizer only by assumption, leading to incomplete analyses and unquantified rates. We also provide an implementable inexact proximal point algorithm yielding new results on minmax problems, and we prove several new useful properties of Riemannian proximal methods: they work when positive curvature is present, the proximal operator does not move points away from any optimizer, and we quantify the smoothness of its induced Moreau envelope. Further, we explore beyond our theory with empirical tests