Competitive tendering and deregulation in the British bus

Item does not contain fulltex

To what extent does the securitisation of asylum seekers contribute to Australia’s failure to meet its relevant international human rights obligations?

BACKGROUND: Although it is well established that late-life depression is associated with both systemic low-graded inflammation and cognitive impairment, the relation between inflammation and cognition in depressed older persons is still equivocal. The objective of this study is to examine the association between plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentrations and cognitive functioning in late-life depression, including the potentially moderating role of sex. METHODS: A total of 369 depressed older persons (>/=60 years) from The Netherlands study of Depression in Older persons (NESDO) were included. Four cognitive domains, i.e. verbal memory, processing speed, interference control and attention were assessed with three cognitive tests (Stroop test, Wais Digit span test, and Rey's verbal learning test). Multiple linear regression analyses were applied with the four cognitive domains as dependent variables adjusted for confounders. RESULTS: The association between NGAL levels and specific cognitive domains were sex-specific. In women, higher NGAL levels were associated with impaired verbal memory and lower processing speed. In men, higher NGAL levels were associated with worse interference control. Higher NGAL levels were not associated with attention. No sex-specific associations of either high sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6) with cognitive functioning were found. CONCLUSION: This study shows sex-specific association of NGAL with cognitive functioning in late-life depression

Cerebrospinal fluid biomarkers for Alzheimer's disease in Down syndrome

Down syndrome (DS), present in nearly six million people, is associated with an extremely high risk to develop Alzheimer's disease (AD). Amyloid-β and tau pathology are omnipresent from age 40 years onward, but clinical symptoms do not appear in all DS individuals. Dementia diagnostics is complex in this population, illustrating the great need for predictive biomarkers. Although blood biomarkers have not yet proven useful, cerebrospinal fluid (CSF) biomarkers (low amyloid-β42, high t-tau, and high p-tau) effectively contribute to AD diagnoses in the general population and are increasingly used in clinical practice. Surprisingly, CSF biomarkers have been barely evaluated in DS. Breaking the taboo on CSF analyses would finally allow for the elucidation of its utility in (differential) diagnoses and staging of disease severity. A sensitive and specific biomarker profile for AD in DS would be of paramount importance to daily care, adaptive caregiving, and specific therapeutic interventions

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Marks of the church in South Africa today - in dialogue with Jurgen Moltmann on his 80th birthday

In this celebration of Moltmann's 80th birthday, an ecclesiological reading of his well known trilogy, Theology of hope, The crucified God, and The church in the power of the Spirit is attempted. It is asserted that Moltmann's discussion of the marks of the church is a high point and summary of his early theological development. These insights are then applied to the situation of the church in South Africa today. The article closes with four contextual questions which are then "answered" in terms of the marks of the church.http://explore.up.ac.za/record=b152516

Waist circumference and Neutrophil Gelatinase-Associated Lipocalin in late-life depression

Item does not contain fulltextBoth visceral obesity and depression are associated with impaired health and excess mortality, possibly through overlapping pathophysiological mechanisms like adipose tissue derived inflammatory markers. These results, however, are primarily based on population-based surveys, often restricted to a young population and depression severity scales instead of patients with established diagnosis of depressive disorder. We examined the relation between waist circumference and late-life depression using the baseline data of the Netherlands Study of Depression in Older people (NESDO). Psychopathology has been assessed with Composite International Diagnostic Interview version 2.1. Adjusted for age, sex, education, lifestyle (smoking, alcohol, physical activity), drug use, cognition and chronic diseases as well as adjusted for body mass index (BMI), analysis of covariance showed that depressed older patients (n=376) had a significantly lower waist circumference (WC) compared to their non-depressed comparisons (n=130): estimated marginal mean (SE)=93.9 (0.5) versus 97.8 (0.8) cm (F=15.9; df=1467; p<.001). Multiple linear regression analyses within the depressed group showed that both, depression severity (Inventory of Depressive Symptoms) as well as duration-related depression characteristics (age of onset, duration of illness, life-time comorbid dysthymia), were associated with the WC. Only the severity of depressive symptoms remained significant after further adjusted for the BMI. Interestingly, a recently discovered adipokine, Neutrophil Gelatinase-Associated Lipocalin (NGAL), was associated with late-life depression, but only in the subgroup of patients with a pathologically increased WC. Population-based findings on the positive association between obesity and depressive symptoms can thus not be generalised to a clinical sample of depressed older patients. The impact of the WC on course and treatment outcome of late-life depression should be examined in clinical samples, taken into account the relative impact of the WC in proportion to the general level of obesity as indexed by the BMI and the role of adipokines

Le rôle des loisirs sportifs dans l'attractivité touristique de la Réunion

OBJECTIVES: To determine whether physical frailty is associated with low-grade inflammation in older adults with depression, because late-life depression is associated with physical frailty and low-grade inflammation. DESIGN: Baseline data of a cohort study. SETTING: Primary care and specialized mental health care. PARTICIPANTS: Individuals aged 60 and older with depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria (N = 366). MEASUREMENTS: The physical frailty phenotype, defined as three out of five criteria (weight loss, weakness, exhaustion, slowness, low physical activity level), and three inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), and neutrophil gelatinase-associated lipocalin (NGAL)) were assessed. RESULTS: The physical frailty phenotype was not associated with inflammatory markers in linear regression models adjusted for sociodemographic characteristics, lifestyle characteristics, and somatic morbidity. Of the individual criteria, handgrip strength was associated with CRP (beta = -0.21, P = .002) and IL-6 (beta = -0.25, P < .001), and gait speed was associated with NGAL (beta = 0.15, P = .02). Principal component analysis identified two dimensions within the physical frailty phenotype: performance-based physical frailty (encompassing gait speed, handgrip strength, and low physical activity) and vitality-based physical frailty (encompassing weight loss and exhaustion). Only performance-based physical frailty was associated with higher levels of inflammatory markers (CRP: beta = 0.14, P = .03; IL-6: beta = 0.13, P = .06; NGAL: beta = 0.14, P = .03). CONCLUSION: The physical frailty phenotype is not a unidimensional construct in individuals with depression. Only performance-based physical frailty is associated with low-grade inflammation in late-life depression, which might point to a specific depressive subtype

Serum NGAL is Associated with Distinct Plasma Amyloid-beta Peptides According to the Clinical Diagnosis of Dementia in Down Syndrome

Item does not contain fulltextBACKGROUND: The majority of people with Down syndrome (DS) develop dementia due to Alzheimer's disease (AD). Neuropathological features are characterized by an accumulation of amyloid-beta (Abeta) deposits and the presence of an activated immune response. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a newly identified (neuro)inflammatory constituent in AD. OBJECTIVE: This study examines NGAL as an inflammatory marker in DS and its associations with plasma Abeta peptides according to the follow-up clinical diagnosis of dementia. METHODS: Baseline serum NGAL and plasma Abeta40, Abeta42, Abetan40, and Abetan42 were quantified in 204 people with DS. The diagnosis of dementia in DS was established by follow-up clinical assessments. The following study groups were characterized: DS with AD at baseline (n = 67), DS without AD (n = 53), and non-demented DS individuals that converted to AD (n = 84). Serum NGAL was analyzed in 55 elderly non-DS, non-demented people. Results : Serum NGAL levels were significantly increased in DS subjects compared to non-DS people. Serum NGAL levels were not associated with clinical dementia symptoms in DS. However, NGAL was positively associated with Abeta42 and Abetan42 in demented DS individuals and with Abeta40 and Abetan40 in the non-demented DS group. NGAL was negatively associated with Abeta42/Abeta40 and Abetan42/Abetan40 ratios in converted DS subjects. These associations persisted for Abetan40, Abeta42/Abeta40, and Abetan42/Abetan40 after adjusting for demographics measures, apolipoprotein E epsilon4 allele, platelets, and anti-inflammatory medication. CONCLUSION: Serum NGAL levels are increased in DS and associated with distinct species of Abeta depending on the progression of dementia as diagnosed by baseline and follow-up clinical assessments