Efficiency of a wide-area survey in achieving short- and long-term warning for small impactors

We consider a network of telescopes capable of scanning all the observable sky each night and targeting Near-Earth objects (NEOs) in the size range of the Tunguska-like asteroids, from 160 m down to 10 m. We measure the performance of this telescope network in terms of the time needed to discover at least 50% of the impactors in the considered population with a warning time large enough to undertake proper mitigation actions. The warning times are described by a trimodal distribution and the telescope network has a 50% probability of discovering an impactor of the Tunguska class with at least one week of advance already in the first 10 yr of operations of the survey. These results suggest that the studied survey would be a significant addition to the current NEO discovery efforts

The National ReferAll Database: An Open Dataset of Exercise Referral Schemes Across the UK

In 2014, The National Institute for Health and Care Excellence (NICE) called for the development of a system to collate local data on exercise referral schemes (ERS). This database would be used to facilitate continued evaluation of ERS. The use of health databases can spur scientific investigation and the generation of evidence regarding healthcare practice. NICE’s recommendation has not yet been met by public health bodies. Through collaboration between ukactive, ReferAll, a specialist in software solutions for exercise referral, and the National Centre for Sport and Exercise Medicine, which has its research hub at the Advanced Wellbeing Research Centre, in Sheffield, data has been collated from multiple UK-based ERS to generate one of the largest databases of its kind. This database moves the research community towards meeting NICEs recommendation. This paper describes the formation and open sharing of The National ReferAll Database, data-cleaning processes, and its structure, including outcome measures. Collating data from 123 ERSs on 39,283 individuals, a database has been created containing both scheme and referral level characteristics in addition to outcome measures over time. The National ReferAll Database is openly available for researchers to interrogate. The National ReferAll Database represents a potentially valuable resource for the wider research community, as well as policy makers and practitioners in this area, which will facilitate a better understanding of ERS and other physical-activity-related social prescribing pathways to help inform public health policy and practice

Functional and Genetic Analysis of Coronavirus Replicase-Transcriptase Proteins

The coronavirus replicase-transcriptase complex is an assembly of viral and cellular proteins that mediate the synthesis of genome and subgenome-sized mRNAs in the virus-infected cell. Here, we report a genetic and functional analysis of 19 temperature-sensitive (ts) mutants of Murine hepatitis virus MHV-A59 that are unable to synthesize viral RNA when the infection is initiated and maintained at the non-permissive temperature. Both classical and biochemical complementation analysis leads us to predict that the majority of MHV-A59 ORF1a replicase gene products (non-structural proteins nsp1–nsp11) form a single complementation group (cistron1) while the replicase gene products encoded in ORF1b (non-structural proteins nsp12–nsp16) are able to function in trans and comprise at least three, and possibly five, further complementation groups (cistrons II–VI). Also, we have identified mutations in the non-structural proteins nsp 4, nsp5, nsp10, nsp12, nsp14, and nsp16 that are responsible for the ts phenotype of eight MHV-A59 mutants, which allows us to conclude that these proteins are essential for the assembly of a functional replicase-transcriptase complex. Finally, our analysis of viral RNA synthesis in ts mutant virus-infected cells allows us to discriminate three phenotypes with regard to the inability of specific mutants to synthesize viral RNA at the non-permissive temperature. Mutant LA ts6 appeared to be defective in continuing negative-strand synthesis, mutant Alb ts16 appeared to form negative strands but these were not utilized for positive-strand RNA synthesis, and mutant Alb ts22 was defective in the elongation of both positive- and negative-strand RNA. On the basis of these results, we propose a model that describes a pathway for viral RNA synthesis in MHV-A59-infected cells. Further biochemical analysis of these mutants should allow us to identify intermediates in this pathway and elucidate the precise function(s) of the viral replicase proteins involved

Eliciting and prioritising determinants of improved care in multimorbidity: A modified online Delphi study.

BACKGROUND: Multimorbidity is a major challenge to health and social care systems around the world. There is limited research exploring the wider contextual determinants that are important to improving care for this cohort. In this study, we aimed to elicit and prioritise determinants of improved care in people with multiple conditions. METHODS: A three-round online Delphi study was conducted in England with health and social care professionals, data scientists, researchers, people living with multimorbidity and their carers. RESULTS: Our findings suggest a care system which is still predominantly single condition focused. 'Person-centred and holistic care' and 'coordinated and joined up care', were highly rated determinants in relation to improved care for multimorbidity. We further identified a range of non-medical determinants that are important to providing holistic care for this cohort. CONCLUSIONS: Further progress towards a holistic and patient-centred model is needed to ensure that care more effectively addresses the complex range of medical and non-medical needs of people living with multimorbidity. This requires a move from a single condition focused biomedical model to a person-based biopsychosocial approach, which has yet to be achieved

Recent advances in understanding resistance exercise training-induced skeletal muscle hypertrophy in humans

Skeletal muscle plays a pivotal role in the maintenance of physical and metabolic health and, critically, mobility. Accordingly, strategies focused on increasing the quality and quantity of skeletal muscle are relevant, and resistance exercise is foundational to the process of functional hypertrophy. Much of our current understanding of skeletal muscle hypertrophy can be attributed to the development and utilization of stable isotopically labeled tracers. We know that resistance exercise and sufficient protein intake act synergistically and provide the most effective stimuli to enhance skeletal muscle mass; however, the molecular intricacies that underpin the tremendous response variability to resistance exercise-induced hypertrophy are complex. The purpose of this review is to discuss recent studies with the aim of shedding light on key regulatory mechanisms that dictate hypertrophic gains in skeletal muscle mass. We also aim to provide a brief up-to-date summary of the recent advances in our understanding of skeletal muscle hypertrophy in response to resistance training in humans

Eliciting and prioritising determinants of improved care in multimorbidity: A modified online Delphi study

BACKGROUND: Multimorbidity is a major challenge to health and social care systems around the world. There is limited research exploring the wider contextual determinants that are important to improving care for this cohort. In this study, we aimed to elicit and prioritise determinants of improved care in people with multiple conditions. METHODS: A three-round online Delphi study was conducted in England with health and social care professionals, data scientists, researchers, people living with multimorbidity and their carers. RESULTS: Our findings suggest a care system which is still predominantly single condition focused. 'Person-centred and holistic care' and 'coordinated and joined up care', were highly rated determinants in relation to improved care for multimorbidity. We further identified a range of non-medical determinants that are important to providing holistic care for this cohort. CONCLUSIONS: Further progress towards a holistic and patient-centred model is needed to ensure that care more effectively addresses the complex range of medical and non-medical needs of people living with multimorbidity. This requires a move from a single condition focused biomedical model to a person-based biopsychosocial approach, which has yet to be achieved

Understanding the effects of nutrition and post-exercise nutrition on skeletal muscle protein turnover: insights from stable isotope studies

Skeletal muscle is the largest organ of the human body and plays a pivotal role in whole-body homeostasis through the maintenance of physical and metabolic health. Establishing strategies aimed at increasing the amount, and minimising loss, of muscle mass are of upmost importance. Muscle mass is primarily dictated by the meal-to-meal fluctuations in muscle protein synthesis (MPS) and muscle protein breakdown (MPB), each of which can be quantified through the use of stable isotopically labelled tracers. Importantly, both MPS and MPB can be influenced by external factors such as nutritional manipulation, specifically protein ingestion, and changes in loading via exercise. To date, research involving stable isotopic tracers has focused on determining the optimal dose, timing surrounding bouts of exercise, distribution and composition of protein to maximally stimulate MPS and inhibit MPB, both at rest and following exercise. In this review we focus on the use of these stable isotopically-labeled tracers to unravel the intricacies of skeletal muscle protein turnover in response to specific nutritional interventions

The direct medical costs of epilepsy in children and young people: a population-based study of health resource utilisation

We described the health resource utilisation (HRU) and associated direct medical costs of managing epilepsy in children and young people (CYP) using population-level data from the United Kingdom. The study cohort were CYP born between 1988 and 2004 who were newly diagnosed with epilepsy and identified using a nationally representative primary care database from the United Kingdom. Reference unit costs were applied to each element of HRU to calculate annual direct medical costs per child. We assessed whether HRU and costs differed by time from diagnosis, age, sex and socioeconomic deprivation. Of 798 CYP newly diagnosed with epilepsy, 56% were male and the mean age at diagnosis was 5.6 years. The highest burden of HRU was in the first year following diagnosis with a mean annual cost of £930 (95% confidence interval (CI) £839–1022) per child in this first year. This decreased to £461 (95%CI 368–551) in the second year which remained fairly constant each subsequent year (£413 (95% CI 282–540) in the 8th year). The highest contribution to the annual medical costs was from inpatient hospital admissions followed by the costs of AEDs. Mean annual medical costs were significantly higher in children under 6 years of age compared with older children (p < 0.01), but were similar across socioeconomic groups (p = 0.62). The direct medical costs of HRU in CYP with epilepsy are higher in the first year after diagnosis compared to subsequent years, reflecting HRU related to the diagnostic process in the first year. Medical costs did not vary substantially by sex or socioeconomic deprivation indicating a similar level of consultation and care across these groups