What factors enable mid-life carers to re-enter the labour market in New Zealand?

Objective.- To assess the characteristics of carers and the caregiving situation associated with return to paid employment among older unemployed carers in New Zealand. Methods.- A baseline sample of 280 unemployed carers was identified from responses by people aged 55-70 to the 2012-2016 biennial waves of the New Zealand Health, Work and Retirement longitudinal survey. Multiple logistic regression analysis was used to assess characteristics uniquely predicting employment status at two-year follow-up. Results.- Sixteen percent were employed at follow-up. Economic living standards, physical health and preference to be in paid employment were positively associated with being employed at follow-up. There were no statistical differences according to age, gender, ethnicity, marital status, education and care characteristics. Conclusion.- Individual preferences were the strongest predictor of return to paid employment. Despite New Zealand employment legislation allowing all employees to request flexible working arrangements, economic and health differences in workforce retention among carers persist

A Natural Plasmid Uniquely Encodes Two Biosynthetic Pathways Creating a Potent Anti-MRSA Antibiotic

Background Understanding how complex antibiotics are synthesised by their producer bacteria is essential for creation of new families of bioactive compounds. Thiomarinols, produced by marine bacteria belonging to the genus Pseudoalteromonas, are hybrids of two independently active species: the pseudomonic acid mixture, mupirocin, which is used clinically against MRSA, and the pyrrothine core of holomycin. Methodology/Principal Findings High throughput DNA sequencing of the complete genome of the producer bacterium revealed a novel 97 kb plasmid, pTML1, consisting almost entirely of two distinct gene clusters. Targeted gene knockouts confirmed the role of these clusters in biosynthesis of the two separate components, pseudomonic acid and the pyrrothine, and identified a putative amide synthetase that joins them together. Feeding mupirocin to a mutant unable to make the endogenous pseudomonic acid created a novel hybrid with the pyrrothine via “mutasynthesis” that allows inhibition of mupirocin-resistant isoleucyl-tRNA synthetase, the mupirocin target. A mutant defective in pyrrothine biosynthesis was also able to incorporate alternative amine substrates. Conclusions/Significance Plasmid pTML1 provides a paradigm for combining independent antibiotic biosynthetic pathways or using mutasynthesis to develop a new family of hybrid derivatives that may extend the effective use of mupirocin against MRSA

Feasibility of implementation of CARD™ for school-based immunizations in Calgary, Alberta: a cluster trial

Background: Negative experiences with school-based immunizations can contribute to vaccine hesitancy in youth and adulthood. We developed an evidence-based, multifaceted and customizable intervention to improve the immunization experience at school called the CARD™ (C-Comfort, A-Ask, R-Relax, D-Distract) system. We evaluated the feasibility of CARD™ implementation for school-based immunizations in Calgary, Canada. Methods: In a mixed methods study, two Community Health Centres providing immunization services, including 5 schools each with grade 9 students (aged approximately 14 years), were randomized to CARD™ or control (usual care). In the CARD™ group, public health staff and students were educated about coping strategies prior to immunization clinics. Clinics were organized to reduce fear and to support student’s choices for coping strategies. Public health staff in the CARD™ group participated in a focus group discussion afterwards. We sought a recruitment rate of 80% for eligible schools, an external stakeholder focus group (e.g., school staff) with 6 or more individuals, 85% of individual injection-related data acquisition (student and immunizer surveys), and 80% absolute agreement between raters for a subset of data that were double-coded. Across focus groups, we examined perceptions of acceptability, appropriateness, feasibility and fidelity of CARD™. Results: Nine (90%) of eligible schools participated. Of 219 students immunized, injection-related student and immunizer data forms were acquired for 195 (89.0%) and 196 (89.5%), respectively. Reliability of data collection was high. Fifteen public health and 5 school staff participated in separate focus groups. Overall, attitudes towards CARD™ were positive and compliance with individual components of CARD™ was high. Public health staff expressed skepticism regarding the value of student participation in the CARD™ system. Suggestions were made regarding processes to refine implementation. Conclusion: While most outcome criteria were satisfied and overall perceptions of implementation outcomes were positive, some important challenges and opportunities were identified. Feedback is being used to inform a large cluster trial that will evaluate the impact of CARD™ during school-based immunizations. Trial registration: The trial is registered at ClinicalTrials.gov (NCT03948633); Submitted April 24, 2019

Gaining user insights into the research-to-operational elements of Impact-based Forecasting (IbF) from within the SHEAR programme : summary of findings

Impact based Forecasting (IbF) is an expanding and evolving area of research within National Meteorological and Hydrological Services (NMHSs) and the humanitarian sector, with a broad aim to enhance communication and timely action to reduce losses associated with natural hazards. Although the principles of IbF may seem new to some disciplines, they leverage knowledge built over several years within the risk and emergency management communities (Smith, 2013) and therefore although its application may be newer to some disciplines, many of the principles and practices are based on existing risk theory concepts. However, a key advance of IbF is the pull-through of these concepts into implementable prototypes, tools and services and in order to do this, a growth in interdisciplinary working. The World Meteorological Organisation (WMO), as well as global Non-Governmental Organisations (e.g. Red Cross Red Crescent) strongly advocate for a shift towards IbF and have developed supporting guidelines (WMO, 2015a; Red Cross Climate Centre, 2020; WMO, 2021) to enhance implementation of such techniques across the globe. In doing this the WMO have distinguished two main types of IbF, subjective and objective. A subjective IbF relies on expert interpretation to provide the impact-based elements to a forecast or warning, whilst an objective IbF utilises vulnerability and exposure datasets, together with hazard information to calculate the risk and/or impacts. It is noted however, that risk assessments almost always utilise a combination of both subjective and objective methods. There are a wide range of dependencies on how an IbF system might evolve, and it is these dependencies which have introduced variety into the approaches and methods used to generate impact-based forecasts and warnings. This variability is also driven by different interpretations of what IbF should provide. Some stakeholders desire to have information on the number of assets or people that might be affected; however, most IbF warnings systems currently provide categorical risk forecasts (i.e. very low, low, medium and high) with supporting generalised impact information. Although the difference between these styles of output may appear subtle it can have significant implications for the development of forecasting and warning applications and the upstream modelling requirements. IbF has rapidly become an umbrella term under which a plethora of methods are being tried and different disciplines engaged. This broad scope is beneficial for research as it enables blue-sky thinking, transdisciplinary research opportunities and ideally, sustained cooperation and collaboration between a wide range of groups (e.g. stakeholders, researchers, technologists, practitioners, decision-makers). However, these same benefits can pose challenges when moving towards operational implementation, particularly for NMHSs with reduced institutional capacities. It should also be noted that the term IbF is linked to a range of other activities and terminologies, including forecast-based action and forecast-based financing (FbF). The lens through which IbF is viewed therefore influences its role and the value it might provide in meeting the objective ‘to enhance usability by making forecasts and warnings more actionable’. Given the growing scope of IbF and the potential challenges this may have for implementation, this research aims to answer the following questions: (1) Is there a shared understanding of what IbF is across individuals involved in its development? (2) Is there a shared perception of the challenges, barriers and opportunities associated with implementing IbF operationally? To accomplish this aim, practitioners, forecasters and researchers, working within the NERC Science for Humanitarian Emergencies and Resilience (SHEAR) Programme, were invited to provide their perspectives on a range of IbF related topics through a set of semi-structured interviews. This report provides a synthesis of the interviewee transcripts from key informant interviews. In section 2 the methodology is described, while section 3 provides a review of the key findings from the complete set of interviews. The final section (section 4) provides recommendations and concluding remarks

Daytime fatigue as a predictor for subsequent retirement among older New Zealand workers

Objectives: There is limited information on the role of fatigue on retirement, either independently or in association with poor sleep. The aim of this study was to examine the prospective association between daytime fatigue, measured as feeling tired or feeling worn out, independently and in relation to dissatisfaction with sleep, and subsequent retirement among 960 older workers in New Zealand. Methods: Data from 2 consecutive surveys (2008 and 2010) of the New Zealand Health, Work, and Retirement Longitudinal Study were used. Poisson regression was used to investigate whether feeling tired and feeling worn out in 2008, along with dissatisfaction with sleep, were associated with self-reported retirement either due to health reasons or other reasons by 2010. Results: The risk for retirement due to health reasons during a 2-year follow-up was 1.80-fold (95% confidence interval [CI] 1.16-2.45) among those who felt tired and 1.99-fold (95% CI 1.34-2.64) among those who felt worn out when compared to those not tired or not feeling worn out after adjusting for several sociodemographic, work characteristics and self-rated health. The risk for retirement due to health reasons was even higher when participant experienced both tiredness and feeling worn out. Dissatisfaction with sleep did not predict retirement due to health or other reasons. Conclusions: Our results highlight that workers at risk of subsequent retirement due to health reasons may be identified with rather simple questions on tiredness and feeling worn out even among generally healthy older workers. </p

Immobilisation induces sizeable and sustained reductions in forearm glucose uptake in just 24h but does not change lipid uptake in healthy men

© 2021 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society Key points: The trajectory, magnitude and localisation of metabolic perturbations caused by immobilisation (IMM) are unresolved. Forearm glucose uptake (FGU) in response to glucose feeding was determined in healthy men before and during 72h of forearm IMM, and the same measurements were made in the non-IMM contralateral limb at baseline and 72h. In a similar study design, FGU and forearm lipid uptake were determined after a high fat mixed-meal (HFMM) in IMM and non-IMM limbs. FGU was reduced by 38%, 57% and 46% following 24, 48 and 72h IMM, respectively, but was unchanged in the non-IMM limb. A similar FGU response to IMM was observed after a HFMM, and forearm lipid uptake was unchanged. A sizeable reduction in FGU occurs in just 24h of IMM, which is sustained thereafter and specific to the IMM limb, making unloading per se the likely rapid driver of dysregulation. Abstract: The trajectory and magnitude of metabolic perturbations caused by muscle disuse are unknown yet central to understanding the mechanistic basis of immobilisation-associated metabolic dysregulation. To address this gap, forearm glucose uptake (FGU) was determined in 10healthy men (age 24.9±0.6years, weight 71.9±2.6 kg, BMI 22.6±0.6kg/m2) during a 180min oral glucose challenge before (0) and after 24, 48 and 72h of arm immobilisation, and before and after 72h in the contralateral non-immobilised arm (Study A). FGU was decreased from baseline at 24h (38%, P=0.04), 48h (57%, P=0.01) and 72h (46%, P=0.06) of immobilisation, and was also 63% less than the non-immobilised limb at 72h (P=0.002). In a second study, FGU and forearm lipid uptake were determined in ninehealthy men (age 22.4±1.3years, weight 71.4±2.8kg, BMI 22.6±0.8kg/m2) during a 420min mixed-meal challenge before (0) and after 24 and 48h of arm immobilisation and before and after 72h in the contralateral non-immobilised arm (Study B). FGU responses were similar to Study A, and forearm lipid uptake was unchanged from pre-immobilisation in both arms over the study. A sizeable decrement in FGU in response to glucose feeding occurred within 24h of immobilisation that was sustained and specific to the immobilised limb. Increasing lipid availability had no additional impact on the rate or magnitude of these responses or on lipid uptake. These findings highlight a lack of muscle contraction per se as a fast-acting physiological insult to FGU

Intramyocellular lipid content and lipogenic gene expression responses following a single bout of resistance type exercise differ between young and older men

The aim of this study was to examine the temporal relationship between intramyocellular lipid (IMCL) content and the expression of genes associated with IMCL turnover, fat metabolism, and inflammation during recovery from an acute bout of resistance type exercise in old versus young men. Seven healthy young (23 ± 2 years, 77.2±2.9 kg) and seven healthy older (72±1 years, 79.3±4.9 kg) males performed a single bout of resistance exercise involving 6 sets of 10 repetitions of leg press and 6 sets of 10 repetitions of leg extension at 75% one-repetition maximum (1-RM).Muscle biopsy samples were obtained before and 12, 24 and 48 h after the completion of exercise and analysed for IMCL content and the expression of 48 genes. The subjects refrained from further heavy physical exercise and consumed a standardized diet for the entire experimental period. The IMCL content was ~2-fold higher at baseline and 12 h post-exercise in old compared with young individuals. However, no differences between groups were apparent after 48 h of recovery. There was higher expression of genes involved in fatty acid synthesis (FASN and PPARγ) during the first 24 h of recovery. Differential responses to exercise were observed between groups for a number of genes indicating increased inflammatory response (IL6, IkBalpha, CREB1) and impaired fat metabolism and TCA cycle (LPL, ACAT1, SUCLG1) in older compared with younger individuals. A singe bout of resistance type exercise leads to molecular changes in skeletal muscle favouring reduced lipid oxidation, increased lipogenesis, and exaggerated inflammation during post-exercise recovery in the older compared with younger individuals, which may be indicative of a blunted response of IMCL turnover with ageing

Evaluating pharmacological THRomboprophylaxis in Individuals undergoing superficial endoVEnous treatment across NHS and private clinics in the UK:a multi-centre, assessor-blind, randomised controlled trial-THRIVE trial

INTRODUCTION: Endovenous therapy is the first choice management for symptomatic varicose veins in NICE guidelines, with 56-70 000 procedures performed annually in the UK. Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a known complication of endovenous therapy, occurring at a rate of up to 3.4%. Despite 73% of UK practitioners administering pharmacological thromboprophylaxis to reduce VTE, no high-quality evidence supporting this practice exists. Pharmacological thromboprophylaxis may have clinical and cost benefit in preventing VTE; however, further evidence is needed. This study aims to establish whether when endovenous therapy is undertaken: a single dose or course of pharmacological thromboprophylaxis alters the risk of VTE; pharmacological thromboprophylaxis is associated with an increased rate of bleeding events; pharmacological prophylaxis is cost effective.METHODS AND ANALYSIS: A multi-centre, assessor-blind, randomised controlled trial (RCT) will recruit 6660 participants from 40 NHS and private sites across the UK. Participants will be randomised to intervention (single dose or extended course of pharmacological thromboprophylaxis plus compression) or control (compression alone). Participants will undergo a lower limb venous duplex ultrasound scan at 21-28 days post-procedure to identify asymptomatic DVT. The duplex scan will be conducted locally by blinded assessors. Participants will be contacted remotely for follow-up at 7 days and 90 days post-procedure. The primary outcome is imaging-confirmed lower limb DVT with or without symptoms or PE with symptoms within 90 days of treatment. The main analysis will be according to the intention-to-treat principle and will compare the rates of VTE at 90 days, using a repeated measures analysis of variance, adjusting for any pre-specified strongly prognostic baseline covariates using a mixed effects logistic regression.ETHICS AND DISSEMINATION: Ethical approval was granted by Brent Research Ethics Committee (22/LO/0261). Results will be disseminated in a peer-reviewed journal and presented at national and international conferences.TRIAL REGISTRATION NUMBER: ISRCTN18501431.</p

Acute effects of prior dietary fat ingestion on postprandial metabolic responses to protein and carbohydrate co-ingestion in overweight and obese men: A randomised crossover trial

Background: Obesity and insulin resistance are associated with an impaired sensitivity to anabolic stimuli such as dietary protein (anabolic resistance). Omega-3 polyunsaturated fatty acids (n-3 PUFA) may be protective against the deleterious effects of saturated fatty acids (SFA) on insulin resistance. However, the contribution of excess fat consumption to anabolic and insulin resistance and the interaction between SFA and n-3 PUFA is not well studied. Aim: The primary aim of this study was to investigate the effects of an oral fat pre-load, with or without the partial substitution of SFA with fish oil (FO)-derived n-3 PUFA, on indices of insulin and anabolic sensitivity in response to subsequent dietary protein and carbohydrate (dextrose) co-ingestion. Methods: Eight middle-aged males with overweight or obesity (52.8 ± 2.0 yr, BMI 31.8 ± 1.4 kg·m−2) ingested either an SFA, or isoenergetic SFA and FO emulsion (FO), or water/control (Con), 4 h prior to a bolus of milk protein and dextrose. Results: Lipid ingestion (in particular FO) impaired the early postprandial uptake of branched chain amino acids (BCAA) into the skeletal muscle in response to protein and dextrose, and attenuated the peak glycaemic response, but was not accompanied by differences in whole body (Matsuda Index: Con: 4.66 ± 0.89, SFA: 5.10 ± 0.94 and FO: 4.07 ± 0.59) or peripheral (forearm glucose netAUC: Con: 521.7 ± 101.7; SFA: 470.2 ± 125.5 and FO: 495.3 ± 101.6 μmol·min−1·100 g lean mass·min [t = 240–420 min]) insulin sensitivity between visits. Postprandial whole body fat oxidation was affected by visit (P = 0.024) with elevated rates in SFA and FO, relative to Con (1.85 ± 0.55; 2.19 ± 0.21 and 0.65 ± 0.35 kJ·h−1·kg−1 lean body mass, respectively), however muscle uptake of free fatty acids (FFA) was unaffected. Conclusion: Oral lipid preloads, consisting of SFA and FO, impair the early postprandial BCAA uptake into skeletal muscle, which occurs independent of changes in insulin sensitivity. Clinical trial registry number: ClinicalTrials.gov Identifier NCT03146286