Effect of low-cost housing on household and environmental health of residents in Phumlani Village, City of Cape Town

Magister Public Health - MPHMany poor households in South Africa find themselves living in informal housing and only become proprietors of formal housing via the government subsidy scheme for core low-cost housing, thereby also realizing their constitutional right to housing. The subsidy is however limited and it largely determines materials, and construction methods used. Obtaining a formal low-cost dwelling means that basic services such as electricity, sanitation, water and waste collection, is available to the home owner. Formal low-cost housing settlements are commonly located in poor areas and recipients of the housing subsidy are commonly unemployed or have low-income jobs, and frequently originate from informal settlements where services, albeit limited and often communal, were provided at no cost. This study sought to assess the combined effect of relocating from an informal dwelling to a formal low-cost dwelling and receiving individual house-based basic services of electricity, water, sanitation and waste collection, on environmental- and household health. An ecological study design was used whereby data was collected at "baseline" while households were living in the informal settlement, and again at "2 years relocated" i.e. 2 years after moving in to the formal low-cost dwelling. The study population included all households residing in the Phumlani- and Pelican Park- Zeekoevlei Informal area in the year 2000, who were on the waiting list to receive low-cost core housing units in Phumlani Village and were due to be relocated there. Due to the rapid pace at which construction of new homes occurred not all households could be captured whilst living in the informal settlement, i.e. at "baseline". The actual sample subsequently consisted of 53 households at "baseline", and all, i.e. 124 households at "2 years relocated". Data was collected via a structured interview, whereby one respondent per household was interviewed by a trained fieldworker. Positive health improvements were reported by households in terms of personal and household health. Significant (p<0.05) positive improvements were found for households in formal lowcost housing at "2 years relocated" for exposures to: overcrowded living conditions (PR=1.159, 95%CI=1.153 – 3.328); indoor air pollution due to cooking and heating (PR=2.185, 95%CI=1.655 – 2.885); improper household waste management (PR=7.381, 95%CI=4.313 – 12.633 and inadequate sanitation (PR=0.365, 95%CI=0.255 – 0.523). The incidence of childhood diarrhoea episodes decreased significantly (PR=5.588, 95%CI=1.284 – 24.315) at "2 years relocated". Water access, availability and use also increased significantly (PR=0.212, 95%CI=0.125 – 0.358) 2 years after relocation. Factors that did not improve include levels of employment for which households were found to be worse off, with 16% of households having no person employed at "2 years relocated" as opposed to only 2% at ‘baseline”. Other factors remaining unchanged included incidences of respiratory, skin and eye infections amongst children ≤ 6 years old. Although exposure levels to indoor air pollution decreased for some households, this remained present for others as electricity in combination with bio-mass fuels are still being used for heating and cooking. Environmental health conditions for a variety of factors remained unchanged and there was a reversion back to living conditions and habits of the informal settlement. Littering, dumping of waste within the neighbourhood and a high pest presence, remained unchanged. Subsidised formal housing and associated basic services does have a positive impact on health. However, the amount of free basic services, specifically electricity, provided, in lieu of household energy requirements, does not satisfactorily cover all household needs. Factors such as unemployment and low-incomes hamper the household’s ability to maintain the electricity supply as is needed and for this reason alternatives to reliance on electricity should be included in the design and construction of the low-cost house. The manifestation of poor environmental health conditions indicates that provision of low-cost housing by itself is not sufficient to ensure good environmental health. Therefore hygiene promotion should be included as part of the total beneficiary package

Towards access for all: 1st Working Group Report for the Global Gene Therapy Initiative (GGTI)

The gene and cell therapy field saw its first approved treatments in Europe in 2012 and the United States in 2017 and is projected to be at least a $10B USD industry by 2025. Despite this success, a massive gap exists between the companies, clinics, and researchers developing these therapeutic approaches, and their availability to the patients who need them. The unacceptable reality is a geographic exclusion of low-and middle-income countries (LMIC) in gene therapy development and ultimately the provision of gene therapies to patients in LMIC. This is particularly relevant for gene therapies to treat human immunodeficiency virus infection and hemoglobinopathies, global health crises impacting tens of millions of people primarily located in LMIC. Bridging this divide will require research, clinical and regulatory infrastructural development, capacity-building, training, an approval pathway and community adoption for success and sustainable affordability. In 2020, the Global Gene Therapy Initiative was formed to tackle the barriers to LMIC inclusion in gene therapy development. This working group includes diverse stakeholders from all sectors and has set a goal of introducing two gene therapy Phase I clinical trials in two LMIC, Uganda and India, by 2024. Here we report on progress to date for this initiative

Ethics of HIV cure research: an unfinished agenda

Background: The pursuit of a cure for HIV is a high priority for researchers, funding agencies, governments and people living with HIV (PLWH). To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure, most of which are early translational research and experimental medicine. As HIV cure research increases, it is critical to identify and address the ethical challenges posed by this research. Methods: We conducted a scoping review of the growing HIV cure research ethics literature, focusing on articles published in English peer-reviewed journals from 2013 to 2021. We extracted and summarized key developments in the ethics of HIV cure research. Twelve community advocates actively engaged in HIV cure research provided input on this summary and suggested areas warranting further ethical inquiry and foresight via email exchange and video conferencing. Discussion: Despite substantial scholarship related to the ethics of HIV cure research, additional attention should focus on emerging issues in six categories of ethical issues: (1) social value (ongoing and emerging biomedical research and scalability considerations); (2) scientific validity (study design issues, such as the use of analytical treatment interruptions and placebos); (3) fair selection of participants (equity and justice considerations); (4) favorable benefit/risk balance (early phase research, benefit-risk balance, risk perception, psychological risks, and pediatric research); (5) informed consent (attention to language, decision-making, informed consent processes and scientific uncertainty); and (6) respect for enrolled participants and community (perspectives of people living with HIV and affected communities and representation). Conclusion: HIV cure research ethics has an unfinished agenda. Scientific research and bioethics should work in tandem to advance ethical HIV cure research. Because the science of HIV cure research will continue to rapidly advance, ethical considerations of the major themes we identified will need to be revisited and refined over time

Environmentally induced DNA methylation is inherited across generations in an aquatic keystone species

Transgenerational inheritance of environmentally induced epigenetic marks can have significant impacts on eco-evolutionary dynamics, but the phenomenon remains controversial in ecological model systems. We used whole-genome bisulfite sequencing of individual water fleas (Daphnia magna) to assess whether environmentally induced DNA methylation is transgenerationally inherited. Genetically identical females were exposed to one of three natural stressors, or a de-methylating drug, and their offspring were propagated clonally for four generations under control conditions. We identified between 70 and 225 differentially methylated CpG positions (DMPs) in F1 individuals whose mothers were exposed to a natural stressor. Roughly half of these environmentally induced DMPs persisted until generation F4. In contrast, treatment with the drug demonstrated that pervasive hypomethylation upon exposure is reset almost completely after one generation. These results suggest that environmentally induced DNA methylation is non-random and stably inherited across generations in Daphnia, making epigenetic inheritance a putative factor in the eco-evolutionary dynamics of freshwater communities

Evidence of a small, island-associated population of common bottlenose dolphins in the Mariana Islands

Small, island-associated populations of cetaceans have evolved around numerous oceanic islands, likely due to habitat discontinuities between nearshore and offshore waters. However, little is known about the ecology and structure of cetacean populations around the Mariana Islands, a remote archipelago in the western Pacific Ocean. We present sighting, photo-identification, and genetic data collected during twelve years of surveys around these islands that reveal the existence of a small, island-associated population of bottlenose dolphins. Nearly half of the photo-identified individuals were encountered in more than one year. Both haplotypic and nuclear genetic diversity among sampled individuals was low (haplotypic diversity = 0.701, nuclear heterozygosity = 0.658), suggesting low abundance. We used mark-recapture analysis of photo-identification data to estimate yearly abundance in the southern portion of the population’s range from 2011 to 2018. Each abundance estimate was less than 54 individuals, with each upper 95% confidence interval below 100. Additional survey effort is necessary to generate a full population abundance estimate. We found extensive introgression of Fraser’s dolphin DNA into both the mitochondrial and nuclear genomes of the population, suggesting at least two hybridization events more than two generations in the past. The Mariana Islands are used extensively by the U.S. military for land and sea training operations. Thus, this unique bottlenose dolphin population likely faces high exposure to multiple threats

Transcriptional diversity during lineage commitment of human blood progenitors.

Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.The work described in this article was primarily supported by the European Commission Seventh Framework Program through the BLUEPRINT grant with code HEALTH-F5-2011-282510 (D.H., F.B., G.C., J.H.A.M., K.D., L.C., M.F., S.C., S.F., and S.P.G.). Research in the Ouwehand laboratory is further supported by program grants from the National Institute for Health Research (NIHR, www.nihr.ac.uk; to A.A., M.K., P.P., S.B.G.J., S.N., and W.H.O.) and the British Heart Foundation under nos. RP-PG-0310-1002 and RG/09/12/28096 (www.bhf.org.uk; to A.R. and W.J.A.). K.F. and M.K. were supported by Marie Curie funding from the NETSIM FP7 program funded by the European Commission. The laboratory receives funding from the NHS Blood and Transplant for facilities. The Cambridge BioResource (www.cambridgebioresource.org.uk), the Cell Phenotyping Hub, and the Cambridge Translational GenOmics laboratory (www.catgo.org.uk) are supported by an NIHR grant to the Cambridge NIHR Biomedical Research Centre (BRC). The BRIDGE-Bleeding and Platelet Disorders Consortium is supported by the NIHR BioResource—Rare Diseases (http://bioresource.nihr.ac.uk/; to E.T., N.F., and Whole Exome Sequencing effort). Research in the Soranzo laboratory (L.V., N.S., and S. Watt) is further supported by the Wellcome Trust (Grant Codes WT098051 and WT091310) and the EU FP7 EPIGENESYS initiative (Grant Code 257082). Research in the Cvejic laboratory (A. Cvejic and C.L.) is funded by the Cancer Research UK under grant no. C45041/A14953. S.J.S. is funded by NIHR. M.E.F. is supported by a British Heart Foundation Clinical Research Training Fellowship, no. FS/12/27/29405. E.B.-M. is supported by a Wellcome Trust grant, no. 084183/Z/07/Z. Research in the Laffan laboratory is supported by Imperial College BRC. F.A.C., C.L., and S. Westbury are supported by Medical Research Council Clinical Training Fellowships, and T.B. by a British Society of Haematology/NHS Blood and Transplant grant. R.J.R. is a Principal Research Fellow of the Wellcome Trust, grant no. 082961/Z/07/Z. Research in the Flicek laboratory is also supported by the Wellcome Trust (grant no. 095908) and EMBL. Research in the Bertone laboratory is supported by EMBL. K.F. and C.v.G. are supported by FWO-Vlaanderen through grant G.0B17.13N. P.F. is a compensated member of the Omicia Inc. Scientific Advisory Board. This study made use of data generated by the UK10K Consortium, derived from samples from the Cohorts arm of the project.This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on 26/9/14 in volume 345, number 6204, DOI: 10.1126/science.1251033. This version will be under embargo until the 26th of March 2015

Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.

The production of megakaryocytes (MKs)--the precursors of blood platelets--from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 10(5) mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology.This work was supported by the Leukemia and Lymphoma Society grant, the UK Medical Research Council (Roger Pedersen), the National Institute for Health Research (NIHR; RP-PG-0310-1002; Willem Ouwehand and Cedric Ghevaert) and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute. Cedric Ghevaert is supported by the British Heart Foundation (FS/09/039); Marloes Tijssen is supported by the European Hematology Association (Research fellowship) and the British Heart Foundation (PG/13/77/30375). Catherine Hobbs was supported by the National Health Service Blood and Transplant. Matthew Trotter was supported by a Medical Research Council Centre grant (MRC Centre for Stem Cell Biology and Regenerative Medicine); since participation in the work described, Matthew Trotter has become an employee of Celgene Research SLU, part of Celgene Corporation. Nicole Soranzo's research and Sanger Institute affiliates are supported by the Wellcome Trust (WT098051 and WT091310), the EU FP7 (Epigenesys 257082 and Blueprint HEAL TH-F5-2011-282510). The Cambridge Biomedical Centre (BRC) hIPSCs core facility is funded by the NIHR.This is the final version of the article. It first appeared from Nature Publishing Group via https://doi.org/10.1038/ncomms1120

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.We thank members of the Cambridge BioResource Scientific Advisory Board and Management Committee for their support of our study and the National Institute for Health Research Cambridge Biomedical Research Centre for funding. K.D. is funded as a HSST trainee by NHS Health Education England. M.F. is funded from the BLUEPRINT Grant Code HEALTH-F5-2011-282510 and the BHF Cambridge Centre of Excellence [RE/13/6/30180]. J.R.S. is funded by a MRC CASE Industrial studentship, co-funded by Pfizer. J.D. is a British Heart Foundation Professor, European Research Council Senior Investigator, and National Institute for Health Research (NIHR) Senior Investigator. S.M., S.T, M.H, K.M. and L.D. are supported by the NIHR BioResource-Rare Diseases, which is funded by NIHR. Research in the Ouwehand laboratory is supported by program grants from the NIHR to W.H.O., the European Commission (HEALTH-F2-2012-279233), the British Heart Foundation (BHF) to W.J.A. and D.R. under numbers RP-PG-0310-1002 and RG/09/12/28096 and Bristol Myers-Squibb; the laboratory also receives funding from NHSBT. W.H.O is a NIHR Senior Investigator. The INTERVAL academic coordinating centre receives core support from the UK Medical Research Council (G0800270), the BHF (SP/09/002), the NIHR and Cambridge Biomedical Research Centre, as well as grants from the European Research Council (268834), the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), Merck and Pfizer. DJR and DA were supported by the NIHR Programme ‘Erythropoiesis in Health and Disease’ (Ref. NIHR-RP-PG-0310-1004). N.S. is supported by the Wellcome Trust (Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH-F5-2011-282510). The INTERVAL study is funded by NHSBT and has been supported by the NIHR-BTRU in Donor Health and Genomics at the University of Cambridge in partnership with NHSBT. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health of England or NHSBT. D.G. is supported by a “la Caixa”-Severo Ochoa pre-doctoral fellowship

Learning to Lead: An Analysis of Current Training Programs for Library Leadership

Leadership concepts and theories began appearing in the library literature in the late 1980s. By the 1990s a number of leadership development programs were being offered that were designed to develop librarian leadership skills. The programs had various objectives: to improve career development of early and midcareer librarians; to provide access to underrepresented minority groups in management; and to develop leadership skills. These programs, primarily multiday and residential in nature, employed a hybrid mix of training methods, including focus on leadership styles, self-discovery, and emphasis on skill-building. Despite the proliferation of these programs, evaluation research about them has primarily focused on self-reports from participants about their learning and their satisfaction with these programs. Systematic evaluation research, particularly utilizing a control group design or providing a longitudinal assessment, has not been widely conducted in the field.published or submitted for publicatio

Health behind bars: can exploring the history of prison health systems impact future policy?

The value of history is, indeed, not scientific but moral … it prepares us to live more humanely in the present, and to meet rather than to foretell, the future - Carl Becker. Becker\u27s quote reminds us of the importance of revealing and understanding historical practices in order to influence actions in the future. There are compelling reasons for uncovering this history, in particular to better inform government policy makers and health advocates, and to address the impacts of growing community expectations to \u27make the punishment fit the crime\u27