1,980 research outputs found

    Transport strategy in Scotland since devolution

    Get PDF
    This article critically reviews how the Scottish Executive's approach to transport has developed since devolution. Although there is much to commend, a number of concerns can be identified, including the possibility that a number of strategic infrastructure schemes appear to have been approved on political rather than on technical grounds. It is difficult to know whether the current set of transport infrastructure investment plans represents good value for public money

    Maternity waiting homes as a costâ effective intervention in rural Liberia

    Full text link
    ObjectiveTo analyze the costâ effectiveness of maternity waiting homes (MWHs) in rural Liberia by examining the cost per life saved and economic effect of MWHs on maternal mortality.MethodsA costâ effectiveness analysis was used to evaluate costs and economic effect of MWHs on maternal mortality in rural Liberia to guide future resource allocation. A secondary data analysis was performed based on a prior quasiâ experimental cohort study of 10 rural primary healthcare facilities, five with a MWH and five without a MWH, that took place from October 30, 2010 to February 28, 2015.ResultsCalculations signified a low cost per year of life saved at MWHs in a rural district in Liberia. Total populationâ adjusted number of women’s lives saved over 3 years was 6.25.ConclusionWhile initial costs were considerable, over a period of 10 or more years MWHs could be a costâ effective and affordable strategy to reduce maternal mortality rates in Liberia. Discussion of the scaling up of MWH interventions for improving maternal outcomes in Liberia and other lowâ and middleâ income countries is justified. Findings can be used to advocate for policy changes to increase the apportionment of resources for building more MWHs in low resource settings.Maternity waiting homes are an affordable and highly costâ effective strategy to decrease maternal mortality in Liberia.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149550/1/ijgo12830.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149550/2/ijgo12830_am.pd

    Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

    Get PDF
    Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1

    The effect of transmucosal 0.2mg/kg Midazolam premedication on dental anxiety, anaesthetic induction and psychological morbidity in children undergoing general anaesthesia for tooth extraction

    Get PDF
    <b>Background:</b> The project aims were to evaluate the benefit of transmucosal Midazolam 0.2mg/kg pre-medication on anxiety, induction behaviour and psychological morbidity in children undergoing general anaesthesia (GA) extractions. <b>Method:</b> 179 children aged 5-10 years (mean 6.53 years) participated in this randomised, double blind, placebo controlled trial. Ninety children had Midazolam placed in the buccal pouch. Dental anxiety was recorded pre operatively and 48 hours later using a child reported MCDAS-FIS scale. Behaviour at anaesthetic induction was recorded and psychological morbidity was scored by the parent using the Rutter Scale pre-operatively and again one-week later. Subsequent dental attendance was recorded at one, three and six months after GA. <b>Results:</b> Whilst levels of mental anxiety did not reduce overall, the most anxious patients demonstrated a reduction in anxiety after receiving midazolam premedicationmay (p=0.01). Neither induction behaviour nor psychological morbidity improved. Irrespective of group, parents reported less hyperactive (p= 0.002) and more prosocial behaviour (p=0.002) after the procedure:;, older children improved most (p=0.048), Post GA Dental attendance was poor and unrelated to after the procedure and unaffected by premedication. <b>Conclusion:</b> 0.2mg/kg buccal Midazolam provided some evidence for reducing anxiety in the most dentally anxious patients. However, induction behaviour, psychological morbidity and subsequent dental attendance were not found to alter between the premedication groups

    <i>C-elegans</i> model identifies genetic modifiers of alpha-synuclein inclusion formation during aging

    Get PDF
    Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a &lt;i&gt;C-elegans&lt;/i&gt; model that makes it possible to monitor, in living animals, the formation of alpha-synuclein inclusions. In worms of old age, inclusions contain aggregated alpha-synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in alpha-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other alpha-synuclein related disorders

    'They never pass me the ball’: exposing ableism through the leisure experiences of disabled children, young people and their families.

    Get PDF
    In this paper, we explore the participation of disabled children, young people and their families in leisure activities. Drawing on the accounts of disabled children, young people and their parents and carers, we reflect on the leisure spaces that they access and record some of their experiences within them. Using the concept of ‘ableism’ (Campbell 2009) we interrogate the data gathered as part a two-year project funded by the Economic and Social Research Council (RES – 062-23-1138) (http//www.rihsc.mmu.ac.uk/postblairproject/):‘Does every child matter, Post-Blair: the interconnections of disabled childhoods'. By doing so we identify some of the inherent and embedded discriminations in favour of those children and young people who are perceived to be ‘able’ that simultaneously work to exclude the young 'kinds of people' (Hacking 2007), categorised as 'disabled', and their families from leisure facilities and opportunities. We suggest that currently, disabled families and children occupy a mix of ‘mainstream', ‘segregated’ and ‘separate’ leisure spaces. We discuss the impact of occupying these spaces and ask: What do the experiences of accessing leisure by disabled children, young people and their families reveal about the processes and practices of ableism? To what extent are children and families required to 'pass'as'normal enough' to gain access to leisure spaces? To what extent are ‘segregated’ leisure opportunities regulated and produced by a kind of ‘diagnostic apartheid’ (Campbell 2008a: 155)? What is the role and value of 'separate' leisure activities? </p

    Safety and immunogenicity of the chlamydia vaccine candidate CTH522 adjuvanted with CAF01 liposomes or aluminium hydroxide: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial

    Get PDF
    BACKGROUND: Chlamydia is the most common sexually transmitted bacterial infection worldwide. National screening programmes and antibiotic treatment have failed to decrease incidence, and to date no vaccines against genital chlamydia have been tested in clinical trials. We aimed to assess the safety and immunogenicity, in humans, of a novel chlamydia vaccine based on a recombinant protein subunit (CTH522) in a prime-boost immunisation schedule. METHODS: This phase 1, first-in-human, double-blind, parallel, randomised, placebo-controlled trial was done at Hammersmith Hospital in London, UK, in healthy women aged 19-45 years. Participants were randomly assigned (3:3:1) to three groups: CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01), CTH522 adjuvanted with aluminium hydroxide (CTH522:AH), or placebo (saline). Participants received three intramuscular injections of 85 μg vaccine (with adjuvant) or placebo to the deltoid region of the arm at 0, 1, and 4 months, followed by two intranasal administrations of 30 μg unadjuvanted vaccine or placebo (one in each nostril) at months 4·5 and 5·0. The primary outcome was safety and the secondary outcome was humoral immunogenicity (anti-CTH522 IgG seroconversion). This study is registered with Clinicaltrials.gov, number NCT02787109. FINDINGS: Between Aug 15, 2016, and Feb 13, 2017, 35 women were randomly assigned (15 to CTH522:CAF01, 15 to CTH522:AH, and five to placebo). 32 (91%) received all five vaccinations and all participants were included in the intention-to-treat analyses. No related serious adverse reactions were reported, and the most frequent adverse events were mild local injection-site reactions, which were reported in all (15 [100%] of 15) participants in the two vaccine groups and in three (60%) of five participants in the placebo group (p=0·0526 for both comparisons). Intranasal vaccination was not associated with a higher frequency of related local reactions (reported in seven [47%] of 15 participants in the active treatment groups vs three [60%] of five in the placebo group; p=1·000). Both CTH522:CAF01 and CTH522:AH induced anti-CTH522 IgG seroconversion in 15 (100%) of 15 participants after five immunisations, whereas no participants in the placebo group seroconverted. CTH522:CAF01 showed accelerated seroconversion, increased IgG titres, an enhanced mucosal antibody profile, and a more consistent cell-mediated immune response profile compared with CTH522:AH. INTERPRETATION: CTH522 adjuvanted with either CAF01 or aluminium hydroxide appears to be safe and well tolerated. Both vaccines were immunogenic, although CTH522:CAF01 had a better immunogenicity profile, holding promise for further clinical development. FUNDING: European Commission and The Innovation Fund Denmark

    Body image, body dissatisfaction and weight status in south asian children: a cross-sectional study

    Get PDF
    Background Childhood obesity is a continuing problem in the UK and South Asian children represent a group that are particularly vulnerable to its health consequences. The relationship between body dissatisfaction and obesity is well documented in older children and adults, but is less clear in young children, particularly South Asians. A better understanding of this relationship in young South Asian children will inform the design and delivery of obesity intervention programmes. The aim of this study is to describe body image size perception and dissatisfaction, and their relationship to weight status in primary school aged UK South Asian children. Methods Objective measures of height and weight were undertaken on 574 predominantly South Asian children aged 5-7 (296 boys and 278 girls). BMI z-scores, and weight status (underweight, healthy weight, overweight or obese) were calculated based on the UK 1990 BMI reference charts. Figure rating scales were used to assess perceived body image size (asking children to identify their perceived body size) and dissatisfaction (difference between perceived current and ideal body size). The relationship between these and weight status were examined using multivariate analyses. Results Perceived body image size was positively associated with weight status (partial regression coefficient for overweight/obese vs. non-overweight/obese was 0.63 (95% CI 0.26-0.99) and for BMI z-score was 0.21 (95% CI 0.10-0.31), adjusted for sex, age and ethnicity). Body dissatisfaction was also associated with weight status, with overweight and obese children more likely to select thinner ideal body size than healthy weight children (adjusted partial regression coefficient for overweight/obese vs. non-overweight/obese was 1.47 (95% CI 0.99-1.96) and for BMI z-score was 0.54 (95% CI 0.40-0.67)). Conclusions Awareness of body image size and increasing body dissatisfaction with higher weight status is established at a young age in this population. This needs to be considered when designing interventions to reduce obesity in young children, in terms of both benefits and harms
    corecore