Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in mycobacterium tuberculosis–infected individuals

Copyright © 2009 by the American Thoracic Society.Rationale: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care. Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. Methods: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. Patients were assessed clinically and had blood samples drawn for immunological analysis over a 52-week period after vaccination with MVA85A. Thoracic computed tomography scans were performed at baseline and at 10 weeks after vaccination. Safety of MVA85A was assessed by clinical, radiological, and inflammatory markers. The immunogenicity of MVA85A was assessed by IFNγ and IL-2 ELISpot assays and FACS. Measurements and Main Results: MVA85A was safe in subjects with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic computed tomography scans after vaccination. MVA85A induced a strong antigen-specific IFN-γ and IL-2 response that was durable for 52 weeks. The magnitude of IFN-γ response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin–vaccinated individuals. Antigen 85A–specific polyfunctional CD4+ T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination. Conclusions: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas.Oxford Biomedical Research Centre, Wellcome Trust, and AFTBVAC

Cryogenic and room temperature strength of sapphire jointed by hydroxide-catalysis bonding

Hydroxide-catalysis bonding is a precision technique used for jointing components in opto-mechanical systems and has been implemented in the construction of quasi-monolithic silica suspensions in gravitational wave detectors. Future detectors are likely to operate at cryogenic temperatures which will lead to a change in test mass and suspension material. One candidate material is mono-crystalline sapphire. Here results are presented showing the influence of various bonding solutions on the strength of the hydroxide-catalysis bonds formed between sapphire samples, measured both at room temperature and at 77 K, and it is demonstrated that sodium silicate solution is the most promising in terms of strength, producing bonds with a mean strength of 63 MPa. In addition the results show that the strengths of bonds were undiminished when tested at cryogenic temperatures

Exploratory analysis of resource demand and the environmental footprint of future aquaculture development using Life Cycle Assessment

Increases in fish demand in the coming decades are projected to be largely met by growth of aquaculture. However, increased aquaculture production is linked to higher demand for natural resources and energy as well as emissions to the environment. This paper explores the use of Life Cycle Assessment to improve knowledge of potential environmental impacts of future aquaculture growth. Different scenarios of future aquaculture development are taken into account in calculating the life cycle environmental impacts. The environmental impact assessments were built on Food and Agriculture Organization statistics in terms of production volume of different species, whereas the inputs and outputs associated with aquaculture production systems were sourced from the literature. The matrix of input-output databases was established through the Blue Frontiers study

Translating concerns into action: a detailed qualitative evaluation of an interdisciplinary intervention on medical wards

Objectives To understand how frontline reports of day-to-day care failings might be better translated into improvement. Design Qualitative evaluation of an interdisciplinary team intervention to capitalise on the frontline experience of care delivery. Prospective clinical team surveillance (PCTS) involved structured interdisciplinary briefings to capture challenges in care delivery, facilitated organisational escalation of the issues they identified, and feedback. Eighteen months of ethnography and two focus groups were conducted with staff taking part in a trial of PCTS. Results PCTS fostered psychological safety – a confidence that the team would not embarrass or punish those who speak up. This was complemented by a hard edge of accountability, whereby team members would regulate their own behaviour in anticipation of future briefings. Frontline concerns were triaged to managers, or resolved autonomously by ward teams, reversing what had been well-established normalisations of deviance. Junior clinicians found a degree of catharsis in airing their concerns, and their teams became more proactive in addressing improvement opportunities. PCTS generated tangible organisational changes, and enabled managers to make a convincing case for investment. However, briefings were constrained by the need to preserve professional credibility, and the relative comfort afforded by the avoidance of accountability. At higher organisational levels, frontline concerns were subject to competition with other priorities, and their resolution was limited by the scale of the challenges they described. Conclusions Prospective safety strategies relying on staff-volunteered data do approximate the realities of frontline care, but still produce acceptable, negotiated accounts, subject to the many interdisciplinary tensions that characterise ward work. Nonetheless, they give managers access to these accounts, and support frontline staff to make incremental changes in their daily work. These are goals for learning healthcare organisations

A special issue of Essays in Biochemistry on structural mass spectrometry

Mass spectrometry (MS) is now established as an analytical tool to interrogate the structure and dynamics of proteins and their assemblies. An array of MS-based technologies has been developed, with each providing unique information pertaining to protein structure, and forming the heart of integrative structural biology studies. This special issue includes a collection of review articles that discuss both established and emerging structural MS methodologies, along with examples of how these technologies are being deployed to interrogate protein structure and function. Combined, this collection highlights the immense potential of the structural MS toolkit in the study of molecular mechanisms underpinning cellular homeostasis and disease

Health-services utilisation amongst older persons during the last year of life: A population-based study

© 2018 The Author(s). Background: Accurate population-based data regarding hospital-based care utilisation by older persons during their last year of life are important in health services planning. We investigated patterns of acute hospital-based service use at the end of life, amongst older decedents in New South Wales (NSW), Australia. Methods: Data from all persons aged ≥70 years who died in the state of NSW Australia in 2007 were included. Several measures of hospital-based service utilisation during the last year of life were assessed from retrospectively linked data comprising data for all registered deaths, cause of death, hospital care during the last year of life (NSW Admitted Patient Data Collection [APDC] and Emergency Department [ED] Data Collection [EDDC]), and the NSW Cancer Registry. Results: Amongst 34,556 decedents aged ≥70 years, 82% (n = 28,366) had ≥1 hospitalisation during the last year of life (median 2), and 21% > 3 hospitalisations. Twenty-five percent (n = 5485) of decedents attended ED during the last week of life. Overall, 21% had a hospitalisation > 30 days in the last year of life, and 7% spent > 3 months in hospital; 79% had ≥1 ED attendance, 17% > 3. Nine percent (n = 3239) spent time in an intensive care unit. Fifty-three percent (n = 18,437) died in an inpatient setting. Hospital records had referenced palliative care for a fifth (7169) of decedents. Adjusting for age group, sex, place of residence, area-level socioeconomic status, and cause of death, having > 3 hospitalisations during the last year of life was more likely for persons dying from cancer (35% versus 16% non-cancer deaths, adjusted odds ratio [aOR] 2.33), 'younger' old decedents (29% for age 70-79 and 20% for age 80-89 versus 11% for 90+, aOR 2.42 and 1.77 respectively) and males (25% versus 17% females, aOR 1.38). Patterns observed for other hospital-based service use were similar. Conclusions: This population-based study reveals high use of hospital care among older persons during their last year of life, although this decreased with increasing older age, providing important data to inform health services planning for this population, and highlighting aspects requiring further study

Beveridge on idleness

Beveridge's wartime proposals to eliminate idleness relied on the precepts of Keynesian economics and substantial extensions in the powers of central government to regulate industry and labour. Using convention theory, this paper demonstrates how these stipulations proved politically untenable. With the disappearance of full employment in the 1980s, the labour market problems Beveridge encountered in his youth have re-emerged accompanied by old problems of working poverty. Established forms of labour market analysis are obsolescent and employment rights disappear. The paper suggests a more decentralized and variable analysis of relations between work and idleness may offer a way forward

Feline parvovirus seroprevalence is high in domestic cats from disease outbreak and non-outbreak regions in Australia

Multiple, epizootic outbreaks of feline panleukopenia (FPL) caused by feline parvovirus (FPV) occurred in eastern Australia between 2014 and 2018. Most affected cats were unvaccinated. We hypothesised that low population immunity was a major driver of re-emergent FPL. The aim of this study was to (i) determine the prevalence and predictors of seroprotective titres to FPV among shelter-housed and owned cats, and (ii) compare the prevalence of seroprotection between a region affected and unaffected by FPL outbreaks. FPV antibodies were detected by haemagglutination inhibition assay on sera from 523 cats and titres ≥1:40 were considered protective. Socioeconomic indices based on postcode and census data were included in the risk factor analysis. The prevalence of protective FPV antibody titres was high overall (94.3%), even though only 42% of cats were known to be vaccinated, and was not significantly different between outbreak and non-outbreak regions. On multivariable logistic regression analysis vaccinated cats were 29.94 times more likely to have protective FPV titres than cats not known to be vaccinated. Cats from postcodes of relatively less socioeconomic disadvantage were 5.93 times more likely to have protective FPV titres. The predictors identified for FPV seroprotective titres indicate targeted vaccination strategies in regions of socioeconomic disadvantage would be beneficial to increase population immunity. The critical level of vaccine coverage required to halt FPV transmission and prevent FPL outbreaks should be determined