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    Thesis (M.S.)--Boston University, 1949. This item was digitized by the Internet Archive

    The prevalence of nevirapine toxicity among pregnant women in three health facilities in Johannesburg: 2004 to 2008 and 2010 to 2011

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    Submitted in partial fulfilment of the requirements for the degree of Master of Public Health, in the field of Maternal and Child Health, to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, September 2014Introduction: Nevirapine (NVP) is used in combination antiretroviral treatment especially for pregnant HIV infected women. NVP has been shown to be inferior and more toxic than other similar drugs, but continues to be used in developing countries due to cost. Aim: This study aimed to determine the prevalence of NVP toxicity and associated factors among 478 pregnant women from three public health facilities in inner city Johannesburg. Materials and methods: We employed a cross-sectional retrospective record review study design to analyse the records of 478 pregnant women in the above mentioned public health facilities. Variables including demographic (age, weight, gestational age) and clinical (CD4 cell count, WHO HIV clinical stage, prior ART experience) characteristics were extracted and the association between these characteristics and the development of toxicity post NVP exposure was explored. Results: The study found that approximately nine out of ten women (89.5%) were ART naïve at the time of NVP initiation. When compared with ART naïve women, ART experienced women had a slightly higher mean CD4 cell count, however, for both groups of women, mean CD4 cell count was less than 250 cells/mm3. Overall, 85.1% of women had a CD4 cell count less than 250 cells/mm3. More than half (55.3%) of the women were in the third trimester of pregnancy and the majority (82%) classified as WHO HIV clinical stage one. At least one adverse event was reported in 63 (13.2%) women. Mild skin rash was the most prevalent adverse event, occurring in 9.6% of women. Hepatotoxicity occurred in 5.3% of women and severe skin rash occurred in 1.5% of women. Almost 85% of adverse events occurred in women with CD4 cell counts <250 cells/mm3. WHO HIV clinical stage II and IV were significantly associated with the overall development of toxicity (ρ <0.01). Conclusions: Whilst the overall prevalence of mild and severe skin rash in this sample was less than that demonstrated in earlier studies, a higher overall prevalence of hepatotoxicity was found. When compared with ART naïve women, ART experienced women were found to have a higher prevalence of mild skin rash. Hepatotoxicity and severe skin rash only occurred in ART naïve women. In this sample, CD4 cell count ≥250 cells/mm3 was not associated with the development of NVP adverse events. Recommendations: Our findings support the continued use of NVP as part of combination ART regimens in women of African descent. In contrast with previously published data, our study showed a significant association between WHO HIV clinical stage and NVP toxicity, our study also included relatively few women with higher CD4 cell counts. Further research including predominantly healthy HIV infected pregnant African women as well as women with higher CD4 cell counts is required in order to fully explore the association between these variables and the development of NVP post-exposure toxicity

    Probing Structural Differences of Recombinant Prion Isoforms Using Fluorescence Spectroscopy

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    Conversion of prion protein (PrP) from its normal, cellular isoform, PrPC, to an infectious, misfolded, fibrillar isoform, PrPSc, is responsible for various neurodegenerative diseases in a variety of mammalian hosts. Although the structure of PrPC is well studied, the structure of PrPSc is not known. Obtaining structural information on the misfolded isoform of prion may lead to preventative therapies and treatments of prion diseases. In this study, six single-tryptophan mutants of recombinant PrP were expressed, purified, and refolded into PrPC or two misfolded isoforms of prion, PrPb and PrPF. Solvent accessibilities of the six tryptophan residues were probed among the three isoforms using various tryptophan fluorescence techniques. For all six mutants, solvent accessibility was shown to decrease following conversion to the misfolded isoforms. Tryptophan accessibility data was used to evaluate two computational models of PrPSc, the beta-helix model and the-beta spiral model, and was also compared with experimental data in literature. Although neither computational model entirely fit the data, the Surewicz model of parallel, in-register beta-strands comprising residues ~160-220 was in agreement with tryptophan accessibilities of residues within this area. However, more structural detail of this experimentally-based model is needed before the two data sets can be fully compared

    Estimating the potential impact of canine distemper virus on the Amur tiger population (Panthera tigris altaica) in Russia

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    Lethal infections with canine distemper virus (CDV) have recently been diagnosed in Amur tigers (Panthera tigris altaica), but long-term implications for the population are unknown. This study evaluates the potential impact of CDV on a key tiger population in Sikhote-Alin Biosphere Zapovednik (SABZ), and assesses how CDV might influence the extinction potential of other tiger populations of varying sizes. An individual-based stochastic, SIRD (susceptible-infected-recovered/dead) model was used to simulate infection through predation of infected domestic dogs, and/or wild carnivores, and direct tiger-to-tiger transmission. CDV prevalence and effective contact based on published and observed data was used to define plausible low- and high-risk infection scenarios. CDV infection increased the 50-year extinction probability of tigers in SABZ by 6.3% to 55.8% compared to a control population, depending on risk scenario. The most significant factors influencing model outcome were virus prevalence in the reservoir population(s) and its effective contact rate with tigers. Adjustment of the mortality rate had a proportional impact, while inclusion of epizootic infection waves had negligible additional impact. Small populations were found to be disproportionately vulnerable to extinction through CDV infection. The 50-year extinction risk in populations consisting of 25 individuals was 1.65 times greater when CDV was present than that of control populations. The effects of density dependence do not protect an endangered population from the impacts of a multi-host pathogen, such as CDV, where they coexist with an abundant reservoir presenting a persistent threat. Awareness of CDV is a critical component of a successful tiger conservation management policy

    Using linked administrative data for monitoring and evaluating the Family Nurse Partnership in England: A scoping report

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    This report, commissioned by the FNP National Unit and undertaken by researchers at UCL and the London School of Hygiene and Tropical Medicine, presents a scoping review of how population-based linkage between data from the Family Nurse Partnership (FNP) in England and administrative datasets from other services could be used to generate evidence for commissioning, service evaluation and research. It addresses the methodological considerations, permission pathways and technical challenges of using data from the FNP linked with routinely collected, administrative data from other public services for population-based analyses, at a national and local authority level. Our ambition, when commissioning this work, was to explore whether linking data from FNP with administrative datasets might help provide a richer view about how the FNP intervention is affecting different cohorts of clients and their child after they have graduated. The report suggests that the potential for data linkage to support ongoing evaluation of a wide range of interventions including FNP at a national level is promising and an important area to explore. It makes a significant contribution to understanding the possibilities and constraints for doing this, which include barriers to data linkage at a local level (which we know is crucial for local commissioners) and the significant investment required to realise the potential of this project. We believe this report offers valuable insights other organisations interested in the delivery of evidence based policy may want to pursue

    An investigation of the relationships between physical health, physical activity and depressive symptomatology among older adults in New Zealand : a thesis presented in partial fulfilment of the requirements for the degree of Masters of Science in Psychology at Massey University, Palmerston North, New Zealand

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    Research has highlighted the importance of understanding potential risk and protective factors in relation to depression among older adults. In particular, the beneficial role of physical activity on depressive symptoms has been previously highlighted. Using the biopsychosocial model of depression this thesis investigated the relationships between physical health, physical activity and depression. The current study utilised data from the 2018 of the Health, Work and Retirement (HWR) survey, on 3919 community-dwelling older people aged between 55 – 70. A series of hierarchical multivariate regressions showed that after controlling for demographic, health variables and anxiety, both physical health and physical activity showed significant negative relationships with depression. Consistent with previous research, and in support of hypotheses those who engaged in more physical activity showed less depressive symptomology and those with poorer health showed more depressive symptomology. However, physical activity did not moderate the relationship between physical health and depression as hypothesised. The current study highlights the need for research on depression among older adults, and the importance of investigating both protective and risk factors for depression. The findings show that poor physical health is a key risk factor for depression and that physical activity is an important consideration among older adults with depression. The current study shows a need for further investigation into protective factors as possible interventions targeting depression among older adults

    Changes in first entry to out-of-home care from 1992 to 2012 among children in England.

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    Placement in out-of-home care (OHC) indicates serious childhood adversity and is associated with multiple adverse outcomes. Each year 0.5% of children in England live in OHC but evidence is lacking on the cumulative proportion who enter during childhood and how this varies over time. We measured the proportion of children born between 1992 and 2011 who entered OHC, including variation in rates of entry over time, and explored the determinants of these changes using decomposition methods. We also described changes in placement type, duration and stability. By age 18, 3.3% of children born 1992-94 entered OHC. This proportion varied by ethnicity (1.6% of White vs. 4.5% of Black children born 2001-03 entered OHC by age 9, 95% CI [1.5-1.7] and [4.4-4.6], p<0.001) and increased over time (0.8% of children born 2009-11 entered OHC by age 1 vs. 0.5% born 1992-94, 95% CI [0.7-0.9] and [0.4-0.6], p<0.001). This overall increase was driven primarily by the increased rate of entry among White children and not by concurrent changes in the population's ethnic composition. The proportion of children entering OHC in England is increasing and characteristics of the care they receive are changing with earlier intervention and longer, more stable placements. Further research is required to understand the reasons for these changes in practice and whether they are cost-effective, sustainable, and improve outcomes for children and society

    Attachment Aware Schools:Working with Families to Enhance Parental Engagement and Home-School Relationships

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    Background:- Application of attachment theory in school contexts lacks empirical evidence. The Attachment Aware Schools pilot project was commissioned by two Local Authorities in England to improve the educational outcomes of Looked After Children, and to build an evidence base. Informed by attachment research, Attachment Aware Schools programs provide a coherent and integrated theoretical framework, discourse, and practice for all practitioners working with children and young people. Objective:- The primary focus was to provide whole school and targeted attachment-based strategies to support children’s well-being, behaviour, and academic attainment. This paper; however, documents a secondary objective, which was to facilitate collaborative partnerships with families. Method:- As part of the mixed methods approach to the Attachment Aware Schools project, a series of case studies were collected and thematically coded. The case studies were generated by practitioners using an outcomes-based framework. Results:- Although the case study sample size is small (N=10), the case studies presented here illustrate how Attachment Aware Schools programs can promote increased home-school engagement and shared practice between home and school. Outcomes include improved home-school relationships, reductions in behavioral incidents, and improved family dynamics. Conclusion:- Attachment Aware Schools can be a vehicle for facilitating supportive home-school collaborative partnerships with positive outcomes for vulnerable children and young people
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