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1.
Glob Health Epidemiol Genom ; 2023: 6693323, 2023.
Article in English | MEDLINE | ID: mdl-37766808

ABSTRACT

Modern biomedical research is characterised by its high-throughput and interdisciplinary nature. Multiproject and consortium-based collaborations requiring meaningful analysis of multiple heterogeneous phenotypic datasets have become the norm; however, such analysis remains a challenge in many regions across the world. An increasing number of data harmonisation efforts are being undertaken by multistudy collaborations through either prospective standardised phenotype data collection or retrospective phenotype harmonisation. In this regard, the Phenotype Harmonisation Working Group (PHWG) of the Human Heredity and Health in Africa (H3Africa) consortium aimed to facilitate phenotype standardisation by both promoting the use of existing data collection standards (hosted by PhenX), adapting existing data collection standards for appropriate use in low- and middle-income regions such as Africa, and developing novel data collection standards where relevant gaps were identified. Ultimately, the PHWG produced 11 data collection kits, consisting of 82 protocols, 38 of which were existing protocols, 17 were adapted, and 27 were novel protocols. The data collection kits will facilitate phenotype standardisation and harmonisation not only in Africa but also across the larger research community. In addition, the PHWG aims to feed back adapted and novel protocols to existing reference platforms such as PhenX.


Subject(s)
Prospective Studies , Humans , Retrospective Studies , Africa , Data Collection , Phenotype
2.
PLoS One ; 14(5): e0215591, 2019.
Article in English | MEDLINE | ID: mdl-31059528

ABSTRACT

INTRODUCTION: Data on the association between HIV infection and deaths from underlying medical conditions are needed to understand and assess the impact of HIV on mortality. We present data on mortality in the Chris Hani Baragwanath Hospital (CHBH) South Africa and analyse the relationship between each cause of death and HIV. METHODS: From 2006 to 2009 data were collected on 15,725 deaths including age, sex, day of admittance and of death, HIV status, ART initiation and CD4+ cell counts. Causes of death associated with HIV were cases, causes of death not associated with HIV were controls. We calculate the odds-ratios (ORs) for being HIV-positive and for each AIDS related condition the disease-attributable fraction (DAF) and the population-attributable fraction (PAF) due to HIV for cases relative to controls. RESULTS: Among those that died, the prevalence of HIV was 61% and of acquired immune deficiency syndrome (AIDS) related conditions was 69%. The HIV-attributable fraction was 36% in the whole sample and 60% in those that were HIV-positive. Cryptococcosis, Kaposi's sarcoma and Pneumocystis jirovecii, TB, gastroenteritis and anaemia were highly predictive of HIV with odds ratios for being HIV-positive ranging from 8 to 124, while genito-urinary conditions, meningitis, other respiratory conditions and sepsis, lymphoma and conditions of skin and bone were significantly associated with HIV with odds ratios for being HIV-positive ranging from 3 to 8. Most of the deaths attributable to HIV were among those dying of TB or of other respiratory conditions. CONCLUSIONS: The high prevalence of HIV among those that died, peaking at 70% in those aged 30 years but still 7% in those aged 80 years, demonstrates the impact of the HIV epidemic on adult mortality and on hospital services and the extent to which early anti-retroviral treatment would have reduced the burden of both. These data make it possible to better assess mortality and morbidity due to HIV in this still high prevalence setting and, in particular, to identify those causes of death that are most strongly associated with HIV.


Subject(s)
HIV Infections/mortality , Hospital Mortality , Adult , Age Factors , Aged , Aged, 80 and over , Case-Control Studies , Cause of Death , Female , Humans , Male , Middle Aged , Odds Ratio , Prevalence , Risk Factors , South Africa/epidemiology
3.
Gerontology ; 64(2): 135-139, 2018.
Article in English | MEDLINE | ID: mdl-28772261

ABSTRACT

The adaptive immune system (AIS) acquires significant deficiency during chronological ageing, making older individuals more susceptible to infections and less responsive to vaccines compared to younger individuals. At the cellular level, one of the most striking features of this ageing-related immune deficiency is the dramatic loss of T-cell diversity that occurs in elderly humans. After the age of 70 years, there is a sharp decline in the diversity of naïve T cells, including a >10-fold decrease in the CD4+ compartment and a >100-fold decrease in the CD8+ compartment. Such changes are detrimental because the AIS relies on a diverse naïve T-cell pool to respond to novel pathogens. Recent work suggests that this collapse of naïve T-cell diversity results from T cells reaching the Hayflick limit and being eliminated through both antigen-dependent and -independent pathways. The progressive attrition of telomeres is the molecular mechanism that underlies this Hayflick limit. Therefore, we propose that by measuring the telomere lengths of T cells with high resolution, it is possible to develop a unique biomarker of immune deficiency, potentially much better correlated with individual susceptibility to diseases compared to chronological age alone.


Subject(s)
Adaptive Immunity , Aging/immunology , Models, Immunological , Aged , Humans , Immunologic Deficiency Syndromes/immunology , Lymphocyte Count , T-Lymphocytes/classification , T-Lymphocytes/immunology , Telomere Shortening/immunology
4.
Nat Genet ; 48(5): 528-36, 2016 05.
Article in English | MEDLINE | ID: mdl-27019111

ABSTRACT

Bats are the only mammals capable of powered flight, but little is known about the genetic determinants that shape their wings. Here we generated a genome for Miniopterus natalensis and performed RNA-seq and ChIP-seq (H3K27ac and H3K27me3) analyses on its developing forelimb and hindlimb autopods at sequential embryonic stages to decipher the molecular events that underlie bat wing development. Over 7,000 genes and several long noncoding RNAs, including Tbx5-as1 and Hottip, were differentially expressed between forelimb and hindlimb, and across different stages. ChIP-seq analysis identified thousands of regions that are differentially modified in forelimb and hindlimb. Comparative genomics found 2,796 bat-accelerated regions within H3K27ac peaks, several of which cluster near limb-associated genes. Pathway analyses highlighted multiple ribosomal proteins and known limb patterning signaling pathways as differentially regulated and implicated increased forelimb mesenchymal condensation in differential growth. In combination, our work outlines multiple genetic components that likely contribute to bat wing formation, providing insights into this morphological innovation.


Subject(s)
Chiroptera/embryology , Chiroptera/genetics , Epigenesis, Genetic , Transcriptome , Wings, Animal/embryology , Animals , Embryonic Development/genetics , Gene Expression Profiling , Genome , Male , RNA, Long Noncoding , Regulatory Sequences, Nucleic Acid , Sequence Analysis, RNA
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