66 research outputs found
A Trial of the Effect of Micronutrient Supplementation on Treatment Outcome, T Cell Counts, Morbidity, and Mortality in Adults with Pulmonary Tuberculosis.
No full textTuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain. We conducted a randomized, double-blind, placebo-controlled trial of micronutrients (vitamins A, B complex, C, and E, as well as selenium) in Dar es Salaam, Tanzania. We enrolled 471 human immunodeficiency virus (HIV)-infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months. Micronutrients decreased the risk ofTB recurrence by 45% overall (95% confidence interval [CI], 7% to 67%; P = .02) and by 63% in HIV-infected patients (95% CI, 8% to 85%; P = .02). There were no significant effects on mortality overall; however, we noted a marginally significant 64% reduction of deaths in HIV-negative subjects (95% CI, -14% to 88%; P = .08). Supplementation increased CD3+ and CD4+ cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients. Micronutrients reduced the incidence of peripheral neuropathy by 57% (95% CI, 41% to 69%; P < .001), irrespective of HIV status. There were no significant effects on weight gain, body composition, anemia, or HIV load. Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania
Transcript-specific expression profiles derived from sequence-based analysis of standard microarrays
No full textBackground: Alternative mRNA processing mechanisms lead to multiple transcripts (i.e. splice isoforms) of a given gene
which may have distinct biological functions. Microarrays like Affymetrix GeneChips measure mRNA expression of genes
using sets of nucleotide probes. Until recently probe sets were not designed for transcript specificity. Nevertheless, the reanalysis of established microarray data using newly defined transcript-specific probe sets may provide information about expression levels of specific transcripts.
Methodology/Principal Findings: In the present study alignment of probe sequences of the Affymetrix microarray HGU133A with Ensembl transcript sequences was performed to define transcript-specific probe sets. Out of a total of 247,965 perfect match probes, 95,008 were designated ‘‘transcript-specific’’, i.e. showing complete sequence alignment, no crosshybridization, and transcript-, not only gene-specificity. These probes were grouped into 7,941 transcript-specific probe sets and 15,619 gene-specific probe sets, respectively. The former were used to differentiate 445 alternative transcripts of 215
genes. For selected transcripts, predicted by this analysis to be differentially expressed in the human kidney, confirmatory real-time RT-PCR experiments were performed. First, the expression of two specific transcripts of the genes PPM1A (PP2CA_HUMAN and P35813) and PLG (PLMN_HUMAN and Q5TEH5) in human kidneys was determined by the transcriptspecific array analysis and confirmed by real-time RT-PCR. Secondly, disease-specific differential expression of single transcripts of PLG and ABCA1 (ABCA1_HUMAN and Q5VYS0_HUMAN) was computed from the available array data sets and confirmed by transcript-specific real-time RT-PCR.
Conclusions: Transcript-specific analysis of microarray experiments can be employed to study gene-regulation on the
transcript level using conventional microarray data. In this study, predictions based on sufficient probe set size and foldchange are confirmed by independent mean
Studies of dijet transverse momentum balance and pseudorapidity distributions in pPb collisions at √sNN=5.02 TeV
No full textOpen Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the
source are credited. Funded by SCOAP3 / License Version CC BY 4.0.Dijet production has been measured in pPb collisions at a nucleon–nucleon centre-of-mass energy of 5.02 TeV . A data sample corresponding to an integrated luminosity of 35 nb −1 was collected using the Compact Muon Solenoid detector at the Large Hadron Collider. The dijet transverse momentum balance, azimuthal angle correlations, and pseudorapidity distributions are studied as a function of the transverse energy in the forward calorimeters ( E 4<|η|<5.2 T ). For pPb collisions, the dijet transverse momentum ratio and the width of the distribution of dijet azimuthal angle difference are comparable to the same quantities obtained from a simulated pp reference and insensitive to E 4<|η|<5.2 T . In contrast, the mean value of the dijet pseudorapidity is found to change monotonically with increasing E 4<|η|<5.2 T , indicating a correlation between the energy emitted at large pseudorapidity and the longitudinal motion of the dijet frame. The pseudorapidity distribution of the dijet system in minimum bias pPb collisions is compared with next-to-leading-order perturbative QCD predictions obtained from both nucleon and nuclear parton distribution functions, and the data more closely match the latter
Genome wide high density SNP-based linkage analysis of childhood absence epilepsy identifies a susceptibility locus on chromosome 3p23-p14
No full textChildhood absence epilepsy (CAE) is an idiopathic generalised epilepsy (IGE) characterised by typical absence seizures manifested by transitory loss of awareness with 2.5–4 Hz spike-wave complexes on ictal EEG. A genetic component to the aetiology is well recognised but the mechanism of inheritance and the genes involved are yet to be fully established.
A genome wide single nucleotide polymorphism (SNP)-based high density linkage scan was carried out using 41 nuclear pedigrees with at least two affected members. Multipoint parametric and non-parametric linkage analyses were performed using MERLIN 1.1.1 and a susceptibility locus was identified on chromosome 3p23-p14 (Zmean = 3.9, p < 0.0001; HLOD = 3.3, α = 0.7). The linked region harbours the functional candidate genes TRAK1 and CACNA2D2. Fine-mapping using a tagSNP approach demonstrated disease association with variants in TRAK1
Will mass drug administration eliminate lymphatic filariasis? Evidence from northern coastal Tanzania
No full textCopyright @ 2012 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and 85 reproduction in any medium, provided the original author and source are credited. The article was made available through the Brunel University Open Access Publishing Fund.This article documents understandings and responses to mass drug administration (MDA) for the treatment and prevention of lymphatic filariasis among adults and children in northern coastal Tanzania from 2004 to 2011. Assessment of village-level distribution registers, combined with self-reported drug uptake surveys of adults, participant observation and interviews, revealed that at study sites in Pangani and Muheza districts the uptake of drugs was persistently low. The majority of people living at these highly endemic locations either did not receive or actively rejected free treatment. A combination of social, economic and political reasons explain the low uptake of drugs. These include a fear of treatment (attributable, in part, to a lack of trust in international aid and a questioning of the motives behind the distribution); divergence between biomedical and local understandings of lymphatic filariasis; and limited and ineffective communication about the rationale for mass treatment. Other contributory factors are the reliance upon volunteers for distribution within villages and, in some locations, strained relationships between different groups of people within villages as well as between local leaders and government officials. The article also highlights a disjuncture between self-reported uptake of drugs by adults at a village level and the higher uptake of drugs recorded in official reports. The latter informs claims that elimination will be a possibility by 2020. This gives voice to a broader problem: there is considerable pressure for those implementing MDA to report positive results. The very real challenges of making MDA work are pushed to one side - adding to a rhetoric of success at the expense of engaging with local realities. It is vital to address the kind of issues raised in this article if current attempts to eliminate lymphatic filariasis in mainland coastal Tanzania are to achieve their goal.This work is funded from the Bill and Melinda Gates Foundation
Beyond recurrent costs: an institutional analysis of the unsustainability of donor-supported reforms in agricultural extension
No full textInternational donors have spent billions of dollars over the past four decades in developing and/or reforming the agricultural extension service delivery arrangements in developing countries. However, many of these reforms, supported through short-term projects, became unsustainable once aid funding had ceased. The unavailability of recurrent funding has predominantly been highlighted in the literature as the key reason for this undesirable outcome, while little has been written about institutional factors. The purpose of this article is to examine the usefulness of taking an institutional perspective in explaining the unsustainability of donor-supported extension reforms and derive lessons for improvement. Using a framework drawn from the school of institutionalism in a Bangladeshi case study, we have found that a reform becomes unsustainable because of poor demands for extension information and advice; missing, weak, incongruent, and perverse institutional frameworks governing the exchange of extension goods (services); and a lack of institutional learning and change during the reform process. Accordingly, we have argued that strategies for sustainable extension reforms should move beyond financial considerations and include such measures as making extension goods (services) more tangible and monetary in nature, commissioning in-depth studies to learn about local institutions, crafting new institutions and/or reforming the weak and perverse institutions prevailing in developing countries. We emphasize the need to address three categories of institutions – regulative, normative, and cultural-cognitive – and call for an alignment among them. We further argue that, in order to be sustainable, a reform should take a systemic approach in institutional capacity building and, for this to be possible, adopt a long-term program approach, as opposed to a short-term project approach
Lipid-soluble Vitamins A, D, and E in HIV-Infected Pregnant women in Tanzania.
No full textThere is limited published research examining lipid-soluble vitamins in human immunodeficiency virus (HIV)-infected pregnant women, particularly in resource-limited settings. This is an observational analysis of 1078 HIV-infected pregnant women enrolled in a trial of vitamin supplementation in Tanzania. Baseline data on sociodemographic and anthropometric characteristics, clinical signs and symptoms, and laboratory parameters were used to identify correlates of low plasma vitamin A (<0.7 micromol/l), vitamin D (<80 nmol/l) and vitamin E (<9.7 micromol/l) status. Binomial regression was used to estimate risk ratios and 95% confidence intervals. Approximately 35, 39 and 51% of the women had low levels of vitamins A, D and E, respectively. Severe anemia (hemoglobin <85 g/l; P<0.01), plasma vitamin E (P=0.02), selenium (P=0.01) and vitamin D (P=0.02) concentrations were significant correlates of low vitamin A status in multivariate models. Erythrocyte Sedimentation Rate (ESR) was independently related to low vitamin A status in a nonlinear manner (P=0.01). The correlates of low vitamin D status were CD8 cell count (P=0.01), high ESR (ESR >81 mm/h; P<0.01), gestational age at enrollment (nonlinear; P=0.03) and plasma vitamins A (P=0.02) and E (P=0.01). For low vitamin E status, the correlates were money spent on food per household per day (P<0.01), plasma vitamin A concentration (nonlinear; P<0.01) and a gestational age <16 weeks at enrollment (P<0.01). Low concentrations of lipid-soluble vitamins are widely prevalent among HIV-infected women in Tanzania and are correlated with other nutritional insufficiencies. Identifying HIV-infected persons at greater risk of poor nutritional status and infections may help inform design and implementation of appropriate interventions
Stress during Pregnancy and Offspring Pediatric Disease: A National Cohort Study
No full textBackground: Identifying risk factors for adverse health outcomes in children is important. The intrauterine environment plays a pivotal role for health and disease across life. Objectives: To conduct a comprehensive study to determine whether common psychosocial stress during pregnancy is a risk factor of a wide spectrum of pediatric diseases in the offspring. Methods: The study was conducted in a population-based sample of mothers with live singleton births (N=66203, 71.4% of those eligible) from the Danish National Birth Cohort, using prospective data. We estimated the association between maternal stress during pregnancy (classified based on two a priori defined indicators of common stress forms, life stress and emotional stress) and offspring diseases during childhood (grouped into 16 categories of ICD-10 diagnoses based on data from national registries), controlling for maternal stress after pregnancy. Results: Median age at end of follow-up was 6.2 (3.6-8.9) years. Life stress (highest compared to lowest quartile) was associated with an increased risk of conditions originating in the perinatal period [odds ratio (OR)=1.13; 95% confidence interval (CI)=1.06-1.21] and congenital malformations (OR=1.17; CI=1.06-1.28), and of the first diagnosis of infection [hazard ratio (HR)=1.28; CI=1.17-1.39], mental disorders (age 0-2.5 years: HR=2.03; CI=1.32-3.14), eye (age 0-4.5 years: HR=1.27; CI=1.06-1.53), ear (HR=1.36; CI=1.23-1.51), respiratory (HR=1.27; CI=1.19-1.35), digestive (HR=1.23; CI=1.11-1.37), skin (HR=1.24; CI=1.09-1.43), musculoskeletal (HR=1.15; CI=1.01-1.30), and genitourinary diseases (HR=1.25; CI=1.08-1.45). Emotional stress was associated with an increased risk for the first diagnosis of infection (HR=1.09; CI=1.01-1.18) and a decreased risk for the first diagnosis of endocrine (HR=0.81; CI=0.67-0.99), eye (HR=0.84; CI=0.71-0.99), and circulatory diseases (age 0-3 years: HR=0.63; CI=0.42-0.95). Conclusions: Maternal life stress during pregnancy be a common risk factor for impaired child health. The results suggest new approaches to reduce childhood diseases
Relationships between anaemia and parasitic infections in Kenyan schoolchildren: a Bayesian hierarchical modelling approach.
No full textAnaemia is multi-factorial in origin and disentangling its aetiology remains problematic, with surprisingly few studies investigating the relative contribution of different parasitic infections to anaemia amongst schoolchildren. We report cross-sectional data on haemoglobin, malaria parasitaemia, helminth infection and undernutrition among 1523 schoolchildren enrolled in classes 5 and 6 (aged 10-21 years) in 30 primary schools in western Kenya. Bayesian hierarchical modelling was used to investigate putative relationships. Children infected with Plasmodium falciparum or with a heavy Schistosoma mansoni infection, stunted children and girls were found to have lower haemoglobin concentrations. Children heavily infected with S. mansoni were also more likely to be anaemic compared with uninfected children. This study further highlights the importance of malaria and intestinal schistosomiasis as contributors to reduced haemoglobin levels among schoolchildren and helps guide the implementation of integrated school health programmes in areas of differing parasite transmission
How Much Help Is Exchanged in Families? Towards an Understanding of Discrepant Research Findings
No full textResponding to claims that contemporary families had abandoned their elderly members, gerontologists over the past 30 years have provided extensive documentation of intergenerational familial support. These studies have been lodged within conceptual frameworks of the modified extended family, intergenerational solidarity, and, more recently, intergenerational equity. By and large, studies claim to have found extensive levels of support. Closer examination of findings from various studies, however, reveals widely discrepant findings in terms of amounts of help given to and received by older family members. This paper examines the findings from four representative Canadian and American studies spanning four decades. Factors contributing to discrepant findings are identified at both methodological and conceptual levels, and implications for future research are discussed.intergenerational support
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