NemaFlex: a microfluidics-based technology for standardized measurement of muscular strength of C. elegans

Muscle strength is a functional measure of quality of life in humans. Declines in muscle strength are manifested in diseases as well as during inactivity, aging, and space travel. With conserved muscle biology, the simple genetic model C. elegans is a high throughput platform in which to identify molecular mechanisms causing muscle strength loss and to develop interventions based on diet, exercise, and drugs. In the clinic, standardized strength measures are essential to quantitate changes in patients; however, analogous standards have not been recapitulated in the C. elegans model since force generation fluctuates based on animal behavior and locomotion. Here, we report a microfluidics-based system for strength measurement that we call ‘NemaFlex’, based on pillar deflection as the nematode crawls through a forest of pillars. We have optimized the micropillar forest design and identified robust measurement conditions that yield a measure of strength that is independent of behavior and gait. Validation studies using a muscle contracting agent and mutants confirm that NemaFlex can reliably score muscular strength in C. elegans. Additionally, we report a scaling factor to account for animal size that is consistent with a biomechanics model and enables comparative strength studies of mutants. Taken together, our findings anchor NemaFlex for applications in genetic and drug screens, for defining molecular and cellular circuits of neuromuscular function, and for dissection of degenerative processes in disuse, aging, and disease

New horizons in the role of digital data in the healthcare of older people

There are national and global moves to improve effective digital data design and application in healthcare. This New Horizons commentary describes the role of digital data in healthcare of the ageing population. We outline how health and social care professionals can engage in the proactive design of digital systems that appropriately serve people as they age, carers and the workforce that supports them.// Key Points: //Healthcare improvements have resulted in increased population longevity and hence multimorbidity.// //Shared care records to improve communication and information continuity across care settings hold potential for older people.// Data structure and coding are key considerations.// A workforce with expertise in caring for older people with relevant knowledge and skills in digital healthcare is important./

Fire as a fundamental ecological process: Research advances and frontiers

© 2020 The Authors. Journal of Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society Fire is a powerful ecological and evolutionary force that regulates organismal traits, population sizes, species interactions, community composition, carbon and nutrient cycling and ecosystem function. It also presents a rapidly growing societal challenge, due to both increasingly destructive wildfires and fire exclusion in fire-dependent ecosystems. As an ecological process, fire integrates complex feedbacks among biological, social and geophysical processes, requiring coordination across several fields and scales of study. Here, we describe the diversity of ways in which fire operates as a fundamental ecological and evolutionary process on Earth. We explore research priorities in six categories of fire ecology: (a) characteristics of fire regimes, (b) changing fire regimes, (c) fire effects on above-ground ecology, (d) fire effects on below-ground ecology, (e) fire behaviour and (f) fire ecology modelling. We identify three emergent themes: the need to study fire across temporal scales, to assess the mechanisms underlying a variety of ecological feedbacks involving fire and to improve representation of fire in a range of modelling contexts. Synthesis: As fire regimes and our relationships with fire continue to change, prioritizing these research areas will facilitate understanding of the ecological causes and consequences of future fires and rethinking fire management alternatives

Relationships between mammographic density, tissue microvessel density, and breast biopsy diagnosis

Association between microvessel density (MVD) and tumor characteristics among breast cancer cases (n = 44). (DOC 54 kb

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Determinants of Physical Health Self-Management Behaviours in Adults With Serious Mental Illness:A Systematic Review

Behavioural interventions can support the adoption of healthier lifestyles and improve physical health outcomes, but it is unclear what factors might drive success of such interventions in people with serious mental illness (SMI). We systematically identified and reviewed evidence of the association between determinants of physical health self-management behaviours in adults with SMI. Data about American Association of Diabetes Educator’s Self-Care Behaviours (AADE-7) were mapped against the novel Mechanisms of Action (MoA) framework. Twenty-eight studies were included in the review, reporting evidence on 104 determinant-behaviour links. Beliefs about capabilities and beliefs about consequences were the most important determinants of behaviour, especially for being physically active and healthy eating. There was some evidence that emotion and environmental context and resources played a role in determining reducing risks, being active, and taking medications. We found very limited evidence associated with problem solving, and no study assessed links between MoAs and healthy coping. Although the review predominantly identified evidence about associations from cross-sectional studies that lacked validated and objective measures of self-management behaviours, these findings can facilitate the identification of behaviour change techniques with hypothesised links to determinants to support self-management in people with SMI

Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma

Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model

The impact of an employee wellness programme in clothing/textile manufacturing companies: a randomised controlled trial

BACKGROUND: The prevalence of health risk behaviours is growing amongst South African employees. Health risk behaviours have been identified as a major contributor to reduced health related quality of life (HRQoL) and the increased prevalence of non-communicable diseases. Worksite wellness programmes promise to promote behaviour changes amongst employees and to improve their HRQoL. The aim of this study was to evaluate the short-term effects of an employee wellness programme on HRQoL, health behaviour change, body mass index (BMI) and absenteeism amongst clothing and textile manufacturing employees. METHODS: The study used a randomised control trial design. The sample consisted of 80 subjects from three clothing manufacturing companies in Cape Town, South Africa. The experimental group was subjected to a wellness programme based on the principles of cognitive behaviour therapy (CBT) as well as weekly supervised exercise classes over six weeks. The control group received a once-off health promotion talk and various educational pamphlets, with no further intervention. Measurements were recorded at baseline and at six weeks post-intervention. Outcome measures included the EQ-5D, Stanford Exercise Behaviours Scale, body mass index and absenteeism.Data was analysed with the Statistica-8 software program. Non-parametric tests were used to evaluate the differences in the medians between the two groups and to determine the level of significance. The Sign test was used to determine the within group changes. The Mann-Whitney U test was used to determine the difference between the two groups. RESULTS: At six weeks post intervention the experimental group (39 subjects) demonstrated improvement in almost every parameter. In contrast, apart from an overall decrease in time off work and a reduction in BMI for all study participants, there was no significant change noted in the behaviour of the control group (41 subjects). Seventy percent of the experimental group had improved HRQoL EQ-5D VAS scores post intervention, indicating improved perceived HRQoL. In comparison, only 58% of the control group had improved HRQoL EQ-5D VAS scores post intervention. There was no significant difference between the two groups at baseline or at six weeks post intervention. CONCLUSION: An employee wellness programme based on the principles of CBT combined with weekly aerobic exercise class was beneficial in improving the perceived HRQoL and changing health-related behaviours of clothing manufacturing employees. However, it cannot be concluded that the EWP was more effective than the once off health promotion talk as no significant changes were noted between the two groups at 6-weeks post intervention.This trial has been registered with ClinicalTrials.gov (trial registration number NCT01625039)

The Atlantic meridional overturning circulation in high resolution models

The Atlantic meridional overturning circulation (AMOC) represents the zonally integrated stream function of meridional volume transport in the Atlantic Basin. The AMOC plays an important role in transporting heat meridionally in the climate system. Observations suggest a heat transport by the AMOC of 1.3 PW at 26°N ‐ a latitude which is close to where the Atlantic northward heat transport is thought to reach its maximum. This shapes the climate of the North Atlantic region as we know it today. In recent years there has been significant progress both in our ability to observe the AMOC in nature and to simulate it in numerical models. Most previous modeling investigations of the AMOC and its impact on climate have relied on models with horizontal resolution that does not resolve ocean mesoscale eddies and the dynamics of the Gulf Stream/North Atlantic Current system. As a result of recent increases in computing power, models are now being run that are able to represent mesoscale ocean dynamics and the circulation features that rely on them. The aim of this review is to describe new insights into the AMOC provided by high‐resolution models. Furthermore, we will describe how high‐resolution model simulations can help resolve outstanding challenges in our understanding of the AMOC