Exercise: The ultimate treatment to all ailments?

Extensive clinical research has provided robust evidence that exercise is a cost-effective measure to substantially alleviate the burden of a large number of diseases, many of which belong to the cardiovascular (CV) spectrum. In terms of cardiac benefit, the positive effects of exercise are attributed to improvements in standard risk factors for atherosclerosis, as well as to its positive impact on several pathophysiological mechanisms for CV diseases. For secondary prevention, exercise, optimally in the context of a cardiac rehabilitation program, has been shown to improve functional capacity and survival. Clinicians should encourage physical activity and provide exercise recommendations for all patients, taking into consideration any underlying pathology. In the present review, the benefits of exercise for the prevention and treatment of major CV risk factors and heart conditions are analyzed

Impact of the ‘Contributing Factors in Construction Accidents’ (ConCA) model

In 2005 the ‘Contributing factors in Construction Accidents’ framework (ConCA) introduced a sociotechnical systems approach to risk management in construction. ConCA demonstrated the value of exploring distal factors and identifying underlying or latent causes: It promoted an understanding of construction accidents as systemic accidents and challenged an industry-wide culture of blaming frontline workers. A decade later the original article has been cited by research from 37 countries, shaping inquiries and initiatives to improve safety in both the UK and Australia. But to what extent has systems thinking infiltrated practitioners and policy-makers’ views? Despite broader views of contributing factors, many practitioners still view workers in a negative light, holding them responsible for accidents because of complacency, cynicism about safety, or a high-tolerance for risk. This paper evaluates the impact of the ConCA framework, updates it, and develops our understanding of the relationships between immediate circumstances and distal factors, as seen by an expert panel of participants (n = 32). A more in-depth ‘ConCA+’ framework is proposed. It challenges the negative perceptions of workers, and supports shifting the emphasis of risk management away from worker behaviors and towards resolving wider systemic issues. New directions are proposed which show how knowledge management, job design, technological innovation, empowerment and collaboration should be the focus of future work

On the bistable zone of milling processes

A modal-based model of milling machine tools subjected to time-periodic nonlinear cutting forces is introduced. The model describes the phenomenon of bistability for certain cutting parameters. In engineering, these parameter domains are referred to as unsafe zones, where steady-state milling may switch to chatter for certain perturbations. In mathematical terms, these are the parameter domains where the periodic solution of the corresponding nonlinear, time-periodic delay differential equation is linearly stable, but its domain of attraction is limited due to the existence of an unstable quasi-periodic solution emerging from a secondary Hopf bifurcation. A semi-numerical method is presented to identify the borders of these bistable zones by tracking the motion of the milling tool edges as they might leave the surface of the workpiece during the cutting operation. This requires the tracking of unstable quasi-periodic solutions and the checking of their grazing to a time-periodic switching surface in the infinite-dimensional phase space. As the parameters of the linear structural behaviour of the tool/machine tool system can be obtained by means of standard modal testing, the developed numerical algorithm provides efficient support for the design of milling processes with quick estimates of those parameter domains where chatter can still appear in spite of setting the parameters into linearly stable domains

The S4–S5 Linker Acts as a Signal Integrator for hERG K+ Channel Activation and Deactivation Gating

Human ether-à-go-go-related gene (hERG) K+ channels have unusual gating kinetics. Characterised by slow activation/deactivation but rapid inactivation/recovery from inactivation, the unique gating kinetics underlie the central role hERG channels play in cardiac repolarisation. The slow activation and deactivation kinetics are regulated in part by the S4–S5 linker, which couples movement of the voltage sensor domain to opening of the activation gate at the distal end of the inner helix of the pore domain. It has also been suggested that cytosolic domains may interact with the S4–S5 linker to regulate activation and deactivation kinetics. Here, we show that the solution structure of a peptide corresponding to the S4–S5 linker of hERG contains an amphipathic helix. The effects of mutations at the majority of residues in the S4–S5 linker of hERG were consistent with the previously identified role in coupling voltage sensor movement to the activation gate. However, mutations to Ser543, Tyr545, Gly546 and Ala548 had more complex phenotypes indicating that these residues are involved in additional interactions. We propose a model in which the S4–S5 linker, in addition to coupling VSD movement to the activation gate, also contributes to interactions that stabilise the closed state and a separate set of interactions that stabilise the open state. The S4–S5 linker therefore acts as a signal integrator and plays a crucial role in the slow deactivation kinetics of the channel

Protoplasmic Astrocytes Enhance the Ability of Neural Stem Cells to Differentiate into Neurons In Vitro

Protoplasmic astrocytes have been reported to exhibit neuroprotective effects on neurons, but there has been no direct evidence for a functional relationship between protoplasmic astrocytes and neural stem cells (NSCs). In this study, we examined neuronal differentiation of NSCs induced by protoplasmic astrocytes in a co-culture model. Protoplasmic astrocytes were isolated from new-born and NSCs from the E13-15 cortex of rats respectively. The differentiated cells labeled with neuron-specific marker β-tubulin III, were dramatically increased at 7 days in the co-culture condition. Blocking the effects of brain-derived neurotrophic factor (BDNF) with an anti-BDNF antibody reduced the number of neurons differentiated from NSCs when co-cultured with protoplasmic astrocytes. In fact, the content of BDNF in the supernatant obtained from protoplasmic astrocytes and NSCs co-culture media was significantly greater than that from control media conditions. These results indicate that protoplasmic astrocytes promote neuronal differentiation of NSCs, which is driven, at least in part, by BDNF

Population-Based Resequencing of Experimentally Evolved Populations Reveals the Genetic Basis of Body Size Variation in Drosophila melanogaster

Body size is a classic quantitative trait with evolutionarily significant variation within many species. Locating the alleles responsible for this variation would help understand the maintenance of variation in body size in particular, as well as quantitative traits in general. However, successful genome-wide association of genotype and phenotype may require very large sample sizes if alleles have low population frequencies or modest effects. As a complementary approach, we propose that population-based resequencing of experimentally evolved populations allows for considerable power to map functional variation. Here, we use this technique to investigate the genetic basis of natural variation in body size in Drosophila melanogaster. Significant differentiation of hundreds of loci in replicate selection populations supports the hypothesis that the genetic basis of body size variation is very polygenic in D. melanogaster. Significantly differentiated variants are limited to single genes at some loci, allowing precise hypotheses to be formed regarding causal polymorphisms, while other significant regions are large and contain many genes. By using significantly associated polymorphisms as a priori candidates in follow-up studies, these data are expected to provide considerable power to determine the genetic basis of natural variation in body size

A perspective on radical transformations to sustainability: resistances, movements and alternatives

A transformation to sustainability calls for radical and systemic societal shifts. Yet what this entails in practice and who the agents of this radical transformation are require further elaboration. This article recenters the role of environmental justice movements in transformations, arguing that the systemic, multi-dimensional and intersectional approach inherent in EJ activism is uniquely placed to contribute to the realization of equitable sustainable futures. Based on a perspective of conflict as productive, and a “conflict transformation” approach that can address the root issues of ecological conflicts and promote the emergence of alternatives, we lay out a conceptual framework for understanding transformations through a power analysis that aims to confront and subvert hegemonic power relations; that is, multi-dimensional and intersectional; balancing ecological concerns with social, economic, cultural and democratic spheres; and is multi-scalar, and mindful of impacts across place and space. Such a framework can help analyze and recognize the contribution of grassroots EJ movements to societal transformations to sustainability and support and aid radical transformation processes. While transitions literature tends to focus on artifacts and technologies, we suggest that a resistance-centred perspective focuses on the creation of new subjectivities, power relations, values and institutions. This recenters the agency of those who are engaged in the creation and recuperation of ecological and new ways of being in the world in the needed transformation

Impact of Selection Bias on Estimation of Subsequent Event Risk

BACKGROUND: Studies of recurrent or subsequent disease events may be susceptible to bias caused by selection of subjects who both experience and survive the primary indexing event. Currently, the magnitude of any selection bias, particularly for subsequent time-to-event analysis in genetic association studies, is unknown. METHODS AND RESULTS: We used empirically inspired simulation studies to explore the impact of selection bias on the marginal hazard ratio for risk of subsequent events among those with established coronary heart disease. The extent of selection bias was determined by the magnitudes of genetic and nongenetic effects on the indexing (first) coronary heart disease event. Unless the genetic hazard ratio was unrealistically large (>1.6 per allele) and assuming the sum of all nongenetic hazard ratios was <10, bias was usually <10% (downward toward the null). Despite the low bias, the probability that a confidence interval included the true effect decreased (undercoverage) with increasing sample size because of increasing precision. Importantly, false-positive rates were not affected by selection bias. CONCLUSIONS: In most empirical settings, selection bias is expected to have a limited impact on genetic effect estimates of subsequent event risk. Nevertheless, because of undercoverage increasing with sample size, most confidence intervals will be over precise (not wide enough). When there is no effect modification by history of coronary heart disease, the false-positive rates of association tests will be close to nominal

Effects of a single intraperitoneal administration of cadmium on femoral bone structure in male rats

<p>Abstract</p> <p>Background</p> <p>Exposure to cadmium (Cd) is considered a risk factor for various bone diseases in humans and experimental animals. This study investigated the acute effects of Cd on femoral bone structure of adult male rats after a single intraperitoneal administration.</p> <p>Methods</p> <p>Ten 4-month-old male Wistar rats were injected intraperitoneally with a single dose of 2 mg CdCl₂/kg body weight and killed 36 h after the Cd had been injected. Ten 4-month-old males served as a control group. Differences in body weight, femoral weight, femoral length and histological structure of the femur were evaluated between the two groups of rats. The unpaired Student's t-test was used for establishment of statistical significance.</p> <p>Results</p> <p>A single intraperitoneal administration of Cd had no significant effect on the body weight, femoral weight or femoral length. On the other hand, histological changes were significant. Rats exposed to Cd had significantly higher values of area, perimeter, maximum and minimum diameters of the primary osteons' vascular canals and Haversian canals. In contrast, a significant decrease in all variables of the secondary osteons was observed in these rats.</p> <p>Conclusions</p> <p>The results indicate that, as expected, a single intraperitoneal administration of 2 mg CdCl₂/kg body weight had no impact on macroscopic structure of rat's femora; however, it affected the size of vascular canals of primary osteons, Haversian canals, and secondary osteons.</p