1,597 research outputs found

    The local economic development processes in low-income countries: the case of the metropolis of Chegutu in Zimbabwe

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    Local authorities are widely regarded as catalysts accelerating localised processes of economic development in industrialised countries but in low-income countries they are perceived as dysfunctional, inefficient and ineffective in meeting and addressing societal demands. This abstract view is however, not grounded in empirical research. As such, utilising the case of the metropolis of Chegutu a survey was designed to empirically explicate the economic processes militating its economic development. The findings are useful to policy-makers, local government authorities and management scholars. The study's unique contribution lies in its examination of the processes of local economic development in a low-income country

    CD4 T Cell Immunity Is Critical for the Control of Simian Varicella Virus Infection in a Nonhuman Primate Model of VZV Infection

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    Primary infection with varicella zoster virus (VZV) results in varicella (more commonly known as chickenpox) after which VZV establishes latency in sensory ganglia. VZV can reactivate to cause herpes zoster (shingles), a debilitating disease that affects one million individuals in the US alone annually. Current vaccines against varicella (Varivax) and herpes zoster (Zostavax) are not 100% efficacious. Specifically, studies have shown that 1 dose of varivax can lead to breakthrough varicella, albeit rarely, in children and a 2-dose regimen is now recommended. Similarly, although Zostavax results in a 50% reduction in HZ cases, a significant number of recipients remain at risk. To design more efficacious vaccines, we need a better understanding of the immune response to VZV. Clinical observations suggest that T cell immunity plays a more critical role in the protection against VZV primary infection and reactivation. However, no studies to date have directly tested this hypothesis due to the scarcity of animal models that recapitulate the immune response to VZV. We have recently shown that SVV infection of rhesus macaques models the hallmarks of primary VZV infection in children. In this study, we used this model to experimentally determine the role of CD4, CD8 and B cell responses in the resolution of primary SVV infection in unvaccinated animals. Data presented in this manuscript show that while CD20 depletion leads to a significant delay and decrease in the antibody response to SVV, loss of B cells does not alter the severity of varicella or the kinetics/magnitude of the T cell response. Loss of CD8 T cells resulted in slightly higher viral loads and prolonged viremia. In contrast, CD4 depletion led to higher viral loads, prolonged viremia and disseminated varicella. CD4 depleted animals also had delayed and reduced antibody and CD8 T cell responses. These results are similar to clinical observations that children with agammaglobulinemia have uncomplicated varicella whereas children with T cell deficiencies are at increased risk of progressive varicella with significant complications. Moreover, our studies indicate that CD4 T cell responses to SVV play a more critical role than antibody or CD8 T cell responses in the control of primary SVV infection and suggest that one potential mechanism for enhancing the efficacy of VZV vaccines is by eliciting robust CD4 T cell responses

    The prognostic significance of micrometastases in node-negative squamous cell carcinoma of the vulva

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    Nodal involvement is one of the most significant prognostic factors in squamous cell carcinoma (SCC) of the vulva. We conducted a retrospective analysis of 31 women with histologically node-negative SCC from a population-based cohort of Grampian women. Median follow-up was 42 months after radical vulvectomy with groin node dissection. In total, 13 women (42%) were found to have micrometastases on immunohistochemistry. The risk of recurrence was almost 20-fold higher in those with micrometastases compared to those without (hazard ratio=19.6 (95% CI 2.3–171)

    Simian Varicella Virus Infection of Rhesus Macaques Recapitulates Essential Features of Varicella Zoster Virus Infection in Humans

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    Simian varicella virus (SVV), the etiologic agent of naturally occurring varicella in primates, is genetically and antigenically closely related to human varicella zoster virus (VZV). Early attempts to develop a model of VZV pathogenesis and latency in nonhuman primates (NHP) resulted in persistent infection. More recent models successfully produced latency; however, only a minority of monkeys became viremic and seroconverted. Thus, previous NHP models were not ideally suited to analyze the immune response to SVV during acute infection and the transition to latency. Here, we show for the first time that intrabronchial inoculation of rhesus macaques with SVV closely mimics naturally occurring varicella (chickenpox) in humans. Infected monkeys developed varicella and viremia that resolved 21 days after infection. Months later, viral DNA was detected only in ganglia and not in non-ganglionic tissues. Like VZV latency in human ganglia, transcripts corresponding to SVV ORFs 21, 62, 63 and 66, but not ORF 40, were detected by RT-PCR. In addition, as described for VZV, SVV ORF 63 protein was detected in the cytoplasm of neurons in latently infected monkey ganglia by immunohistochemistry. We also present the first in depth analysis of the immune response to SVV. Infected animals produced a strong humoral and cell-mediated immune response to SVV, as assessed by immunohistology, serology and flow cytometry. Intrabronchial inoculation of rhesus macaques with SVV provides a novel model to analyze viral and immunological mechanisms of VZV latency and reactivation

    Ethnic inequalities and pathways to care in psychosis in England: a systematic review and meta-analysis

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    Š The Author(s). 2018Background: As part of a national programme to tackle ethnic inequalities, we conducted a systematic review and meta-analysis of research on ethnic inequalities in pathways to care for adults with psychosis living in England and/or Wales. Methods: Nine databases were searched from inception to 03.07.17 for previous systematic reviews, including forward and backward citation tracking and a PROSPERO search to identify ongoing reviews. We then carried forward relevant primary studies from included reviews (with the latest meta-analyses reporting on research up to 2012), supplemented by a search on 18.10.17 in MEDLINE, Embase, PsycINFO and CINAHL for primary studies between 2012 and 2017 that had not been covered by previous meta-analyses. Results: Forty studies, all conducted in England, were included for our updated meta-analyses on pathways to care. Relative to the White reference group, elevated rates of civil detentions were found for Black Caribbean (OR = 3.43, 95% CI = 2.68 to 4.40, n = 18), Black African (OR = 3.11, 95% CI = 2.40 to 4.02, n = 6), and South Asian patients (OR = 1.50, 95% CI 1.07 to 2.12, n = 10). Analyses of each Mental Health Act section revealed significantly higher rates for Black people under (civil) Section 2 (OR = 1.53, 95% CI = 1.11 to 2.11, n = 3). Rates in repeat admissions were significantly higher than in first admission for South Asian patients (between-group difference p < 0.01). Some ethnic groups had more police contact (Black African OR = 3.60, 95% CI = 2.15 to 6.05, n = 2; Black Caribbean OR = 2.64, 95% CI = 1.88 to 3.72, n = 8) and criminal justice system involvement (Black Caribbean OR = 2.76, 95% CI = 2.02 to 3.78, n = 5; Black African OR = 1.92, 95% CI = 1.32 to 2.78, n = 3). The White Other patients also showed greater police and criminal justice system involvement than White British patients (OR = 1.49, 95% CI = 1.03 to 2.15, n = 4). General practitioner involvement was less likely for Black than the White reference group. No significant variations over time were found across all the main outcomes. Conclusions: Our updated meta-analyses reveal persisting but not significantly worsening patterns of ethnic inequalities in pathways to psychiatric care, particularly affecting Black groups. This provides a comprehensive evidence base from which to inform policy and practice amidst a prospective Mental Health Act reform. Trial registration: CRD42017071663Peer reviewedFinal Published versio

    Prevalence and Subtypes of Mild Cognitive Impairment in Parkinson's Disease.

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    The current study examined the prevalence and subtypes of Mild Cognitive Impairment (MCI) in an Australian sample of people with Parkinson's Disease (PD). Seventy participants with PD completed neuropsychological assessments of their cognitive performance, using MDS Task Force Level II diagnostic criteria for PD-MCI. A cut-off score of less than one standard deviation (SD) below normative data determined impaired performance on a neuropsychological test. Of 70 participants, 45 (64%) met Level II diagnostic criteria for PD-MCI. Among those with PD-MCI, 42 (93%) were identified as having multiple domain impairment (28 as amnestic multiple domain and 14 as nonamnestic multiple domain). Single domain impairment was less frequent (2 amnestic/1 nonamnestic). Significant differences were found between the PD-MCI and Normal Cognition groups, across all cognitive domains. Multiple domain cognitive impairment was more frequent than single domain impairment in an Australian sample of people with PD. However, PD-MCI is heterogeneous and current prevalence and subtyping statistics may be an artifact of variable application methods of the criteria (e.g., cut off scores and number of tests). Future longitudinal studies refining the criteria will assist with subtyping the progression of PD-MCI, while identifying individuals who may benefit from pharmacological and nonpharmacological interventions

    Marine ecosystem response to the Atlantic Multidecadal Oscillation.

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    Against the backdrop of warming of the Northern Hemisphere it has recently been acknowledged that North Atlantic temperature changes undergo considerable variability over multidecadal periods. The leading component of natural low-frequency temperature variability has been termed the Atlantic Multidecadal Oscillation (AMO). Presently, correlative studies on the biological impact of the AMO on marine ecosystems over the duration of a whole AMO cycle (∟60 years) is largely unknown due to the rarity of continuously sustained biological observations at the same time period. To test whether there is multidecadal cyclic behaviour in biological time-series in the North Atlantic we used one of the world's longest continuously sustained marine biological time-series in oceanic waters, long-term fisheries data and historical records over the last century and beyond. Our findings suggest that the AMO is far from a trivial presence against the backdrop of continued temperature warming in the North Atlantic and accounts for the second most important macro-trend in North Atlantic plankton records; responsible for habitat switching (abrupt ecosystem/regime shifts) over multidecadal scales and influences the fortunes of various fisheries over many centuries

    Methods of identifying and recruiting older people at risk of social isolation and loneliness: A mixed methods review

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    BackgroundLoneliness and social isolation are major determinants of mental wellbeing, especially among older adults. The effectiveness of interventions to address loneliness and social isolation among older adults has been questioned due to the lack of transparency in identifying and recruiting populations at risk. This paper aims to systematically review methods used to identify and recruit older people at risk of loneliness and social isolation into research studies that seek to address loneliness and social isolation.MethodsIn total, 751 studies were identified from a structured search of eleven electronic databases combined with hand searching of reference bibliography from identified studies for grey literature. Studies conducted between January 1995 and December 2017 were eligible provided they recruited community living individuals aged 50 and above at risk of social isolation or loneliness into an intervention study.ResultA total of 22 studies were deemed eligible for inclusion. Findings from these studies showed that the most common strategy for inviting people to participate in intervention studies were public-facing methods including mass media and local newspaper advertisements. The majority of participants identified this way were self-referred, and in many cases self-identified as lonely. In most cases, there was no standardised tool for defining loneliness or social isolation. However, studies that recruited via referral by recognised agencies reported higher rates of eligibility and enrolment. Referrals from primary care were only used in a few studies. Studies that included agency referral either alone or in combination with multiple forms of recruitment showed more promising recruitment rates than those that relied on only public facing methods. Further research is needed to establish the cost-effectiveness of multiple forms of referral.ConclusionFindings from this study demonstrate the need for transparency in writing up the methods used to approach, assess and enrol older adults at risk of becoming socially isolated. None of the intervention studies included in this review justified their recruitment strategies. The ability of researchers to share best practice relies greatly on the transparency of research

    Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

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    The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
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