Do our leaders believe in a fair go? Prime Minister Malcolm Turnbull has stated that he and his wife Lucy have been lucky and observed that 'there are taxi drivers that work harder than I ever have ...and they don't have much money'.
Do our leaders believe in a fair go? Prime Minister Malcolm Turnbull has stated that he and his wife Lucy have been lucky and observed that 'there are taxi drivers that work harder than I ever have ...and they don't have much money'.
•We present the first WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.•Globally in 2016, 488 million people were exposed to long working hours (≥55 hours/week).•This exposure ...had 745,194 attributable deaths and 23.3 million DALYs from ischemic heart disease and stroke.•These are 4.9% of all deaths and 6.9% of all DALYs from these causes.•The Western Pacific, South-East Asia, men, and older people carried higher burdens.
World Health Organization (WHO) and International Labour Organization (ILO) systematic reviews reported sufficient evidence for higher risks of ischemic heart disease and stroke amongst people working long hours (≥55 hours/week), compared with people working standard hours (35–40 hours/week). This article presents WHO/ILO Joint Estimates of global, regional, and national exposure to long working hours, for 194 countries, and the attributable burdens of ischemic heart disease and stroke, for 183 countries, by sex and age, for 2000, 2010, and 2016.
We calculated population-attributable fractions from estimates of the population exposed to long working hours and relative risks of exposure on the diseases from the systematic reviews. The exposed population was modelled using data from 2324 cross-sectional surveys and 1742 quarterly survey datasets. Attributable disease burdens were estimated by applying the population-attributable fractions to WHO’s Global Health Estimates of total disease burdens.
In 2016, 488 million people (95% uncertainty range: 472–503 million), or 8.9% (8.6–9.1) of the global population, were exposed to working long hours (≥55 hours/week). An estimated 745,194 deaths (705,786–784,601) and 23.3 million disability-adjusted life years (22.2–24.4) from ischemic heart disease and stroke combined were attributable to this exposure. The population-attributable fractions for deaths were 3.7% (3.4–4.0) for ischemic heart disease and 6.9% for stroke (6.4–7.5); for disability-adjusted life years they were 5.3% (4.9–5.6) for ischemic heart disease and 9.3% (8.7–9.9) for stroke.
WHO and ILO estimate exposure to long working hours (≥55 hours/week) is common and causes large attributable burdens of ischemic heart disease and stroke. Protecting and promoting occupational and workers’ safety and health requires interventions to reduce hazardous long working hours.
The ability to reproducibly load bioactive molecules into polymeric microspheres is a challenge. Traditional microsphere fabrication methods typically provide inhomogeneous release profiles and ...suffer from lack of batch to batch reproducibility, hindering their potential to up-scale and their translation to the clinic. This deficit in homogeneity is in part attributed to broad size distributions and variability in the morphology of particles. It is thus desirable to control morphology and size of non-loaded particles in the first instance, in preparation for obtaining desired release profiles of loaded particles in the later stage. This is achieved by identifying the key parameters involved in particle production and understanding how adapting these parameters affects the final characteristics of particles. In this study, electrospraying was presented as a promising technique for generating reproducible particles made of polycaprolactone, a biodegradable, FDA-approved polymer. Narrow size distributions were obtained by the control of electrospraying flow rate and polymer concentration, with average particle sizes ranging from 10 to 20 µm. Particles were shown to be spherical with a homogeneous embossed texture, determined by the polymer entanglement regime taking place during electrospraying. No toxic residue was detected by this process based on preliminary cell work using DNA quantification assays, validating this method as suitable for further loading of bioactive components.
Radiomics, the high-throughput mining of quantitative image features from standard-of-care medical imaging that enables data to be extracted and applied within clinical-decision support systems to ...improve diagnostic, prognostic, and predictive accuracy, is gaining importance in cancer research. Radiomic analysis exploits sophisticated image analysis tools and the rapid development and validation of medical imaging data that uses image-based signatures for precision diagnosis and treatment, providing a powerful tool in modern medicine. Herein, we describe the process of radiomics, its pitfalls, challenges, opportunities, and its capacity to improve clinical decision making, emphasizing the utility for patients with cancer. Currently, the field of radiomics lacks standardized evaluation of both the scientific integrity and the clinical relevance of the numerous published radiomics investigations resulting from the rapid growth of this area. Rigorous evaluation criteria and reporting guidelines need to be established in order for radiomics to mature as a discipline. Herein, we provide guidance for investigations to meet this urgent need in the field of radiomics.
In 2002, the joint International Programme on Chemical Safety (IPCS) of the World Health Organization (WHO), the United Nations Environment Programme (UNEP), and the International Labour Organisation ...(ILO) published a report titled Global Assessment of the State-of-the-Science of Endocrine Disruptors (http://www.who.int/ipcs/publications/new_issues/endocrine_disruptors/en/). Since 2002, intense scientific work has improved our understanding of the impacts of endocrine-disrupting chemicals (EDCs) on human and wildlife health, such that in 2012, the UNEP and WHO, in collaboration with international experts, have produced an updated document on EDCs, State of the Science of Endocrine Disrupting Chemicals - 2012 (http://www.who.int/ceh/publications/endocrine/en/index.html) that includes scientific information on human and wildlife impacts and lists key concerns for decision makers and others concerned about the future of human and wildlife health.
Chandelier (axoaxonic) cells (ChCs) are a distinct group of GABAergic interneurons that innervate the axon initial segments of pyramidal cells. However, their circuit role and the function of their ...clearly defined anatomical specificity remain unclear. Recent work has demonstrated that chandelier cells can produce depolarizing GABAergic PSPs, occasionally driving postsynaptic targets to spike. On the other hand, other work suggests that ChCs are hyperpolarizing and may have an inhibitory role. These disparate functional effects may reflect heterogeneity among ChCs. Here, using brain slices from transgenic mouse strains, we first demonstrate that, across different neocortical areas and genetic backgrounds, upper Layer 2/3 ChCs belong to a single electrophysiologically and morphologically defined population, extensively sampling Layer 1 inputs with asymmetric dendrites. Consistent with being a single cell type, we find electrical coupling between ChCs. We then investigate the effect of chandelier cell activation on pyramidal neuron spiking in several conditions, ranging from the resting membrane potential to stimuli designed to approximate in vivo membrane potential dynamics. We find that under quiescent conditions, chandelier cells are capable of both promoting and inhibiting spike generation, depending on the postsynaptic membrane potential. However, during in vivo-like membrane potential fluctuations, the dominant postsynaptic effect was a strong inhibition. Thus, neocortical chandelier cells, even from within a homogeneous population, appear to play a dual role in the circuit, helping to activate quiescent pyramidal neurons, while at the same time inhibiting active ones.
•Non-aqueous dispersion is used for protein loading in electrosprayed microparticles.•Polyethylene glycol (PEG) is used as a micronizing and solubilizing agent.•Electrospraying parameters control ...particle size distributions and morphologies.•Micron-size protein particles are evenly loaded in polycaprolactone particles.•PEG molecular weight tailors release profiles via microparticle size distributions.
The fabrication of tailored microparticles for delivery of therapeutics is a challenge relying upon a complex interplay between processing parameters and materials properties. The emerging use of electrospraying allows better tailoring of particle morphologies and sizes than current techniques, critical to reproducible release profiles. While dry encapsulation of proteins is essential for the release of active therapeutics from microparticles, it is currently uncharacterized in electrospraying. To this end, poly(ethylene glycol) (PEG) was assessed as a micronizing and solubilizing agent for dry protein encapsulation and release from electrosprayed particles made from polycaprolactone (PCL). The physical effect of PEG in protein-loaded poly(lactic-co-glycolic acid) (PLGA) particles was also studied, for comparison. The addition of 5–15wt% PEG 6kDa or 35kDa resulted in reduced PCL particle sizes and broadened distributions, which could be improved by tailoring the electrospraying processing parameters, namely by reducing polymer concentration and increasing flow rate. Upon micronization, protein particle size was reduced to the micrometer domain, resulting in homogenous encapsulation in electrosprayed PCL microparticles. Microparticle size distributions were shown to be the most determinant factor for protein release by diffusion and allowed specific control of release patterns.
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