A Novel Exercise Initiative for Seniors to Improve Balance and Physical Function.

OBJECTIVE: To investigate the feasibility, effectiveness, and short-term effects of an exercise intervention using a novel exercise park in improving seniors' balance, physical function, and quality of life. METHOD: Randomized controlled trial with pre- and post-intervention design (baseline and 18-week intervention) was used. Outcome measures included measures of balance, strength, and function, as well as quality of life and fear of falling. MANCOVA was used to assess differences between groups (control and exercise intervention) over time. RESULTS: Intervention group showed significant improvement on single leg stance (p = .02, 95% confidence interval [CI] = [-8.35, -0.549]), knee strength (p < .01, 95% CI = [-29.14, -5.86]), 2-min walk (p = 0.02, 95% CI = [-19.13, -0.859]), and timed sit to stand (p = .03, 95% CI = [-2.26, -0.143]) tests. DISCUSSION: The exercise park program improved physical function and had high adherence and participation rate. Such intervention has been shown to be safe and therefore might enhance participation in exercise programs for older adults

One Health, One National Park: A Contribution to New Perspectives and Economics for Modern Times

One Health is a concept that sees human, animal, and environmental health as parts of a single interdependent system. The Covid-19 pandemic, its implications reaching far beyond the direct effects of a coronavirus on people’s health, underlines the importance of this increasingly influential perspective. In practice, One Health has its roots in early affiliations of human and animal health science. Over time, each sphere of inquiry evolved to address its own agenda. Recently, veterinary scientists have led the reintegration, extension, and promotion of One Health sciences to address modern-day problems in which health and people’s general wellbeing are viewed as inseparable. A prerequisite is to set out a framework of concepts and principles enabling clear definition of problems, interrelationships needing to be understood, and the level of aggregation appropriate for quantitative analysis. This paper extends the framework by considering economic trade-offs that inevitably must be made in the human, animal, and environmental sub-systems, and the consequences when policy interventions are superimposed on them. The New Forest National Park in southern England is a case where this perspective is essential. Following the Stone Mountain definition of One Health, first a conventional approach linking human and animal health is taken. Lyme disease, Alabama rot, bovine tuberculosis and strangles are examples of diseases known to be of significant concern. The focus is finding scope for socially efficient risk reduction in response to mitigation resource use. Superimposed on the grazing livestock subsystems are support payments for commoner farmers. The financial incentives provided by what effectively are headage payments have caused animal inventories to grow so much that the wider environment may well be subject to adverse spillover effects that merit investigation

Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Increased peri-ductal collagen micro-organization may contribute to raised mammographic density

BACKGROUND: High mammographic density is a therapeutically modifiable risk factor for breast cancer. Although mammographic density is correlated with the relative abundance of collagen-rich fibroglandular tissue, the causative mechanisms, associated structural remodelling and mechanical consequences remain poorly defined. In this study we have developed a new collaborative bedside-to-bench workflow to determine the relationship between mammographic density, collagen abundance and alignment, tissue stiffness and the expression of extracellular matrix organising proteins. METHODS: Mammographic density was assessed in 22 post-menopausal women (aged 54–66 y). A radiologist and a pathologist identified and excised regions of elevated non-cancerous X-ray density prior to laboratory characterization. Collagen abundance was determined by both Masson’s trichrome and Picrosirius red staining (which enhances collagen birefringence when viewed under polarised light). The structural specificity of these collagen visualisation methods was determined by comparing the relative birefringence and ultrastructure (visualised by atomic force microscopy) of unaligned collagen I fibrils in reconstituted gels with the highly aligned collagen fibrils in rat tail tendon. Localised collagen fibril organisation and stiffness was also evaluated in tissue sections by atomic force microscopy/spectroscopy and the abundance of key extracellular proteins was assessed using mass spectrometry. RESULTS: Mammographic density was positively correlated with the abundance of aligned periductal fibrils rather than with the abundance of amorphous collagen. Compared with matched tissue resected from the breasts of low mammographic density patients, the highly birefringent tissue in mammographically dense breasts was both significantly stiffer and characterised by large (>80 μm long) fibrillar collagen bundles. Subsequent proteomic analyses not only confirmed the absence of collagen fibrosis in high mammographic density tissue, but additionally identified the up-regulation of periostin and collagen XVI (regulators of collagen fibril structure and architecture) as potential mediators of localised mechanical stiffness. CONCLUSIONS: These preliminary data suggest that remodelling, and hence stiffening, of the existing stromal collagen microarchitecture promotes high mammographic density within the breast. In turn, this aberrant mechanical environment may trigger neoplasia-associated mechanotransduction pathways within the epithelial cell population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0664-2) contains supplementary material, which is available to authorized users

Subsequent Event Risk in Individuals with Established Coronary Heart Disease:Design and Rationale of the GENIUS-CHD Consortium

BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators

Conceptualising the technical relationship of animal disease surveillance to intervention and mitigation as a basis for economic analysis

<p>Abstract</p> <p>Background</p> <p>Surveillance and intervention are resource-using activities of strategies to mitigate the unwanted effects of disease. Resources are scarce, and allocating them to disease mitigation instead of other uses necessarily involves the loss of alternative sources of benefit to people. For society to obtain the maximum benefits from using resources, the gains from disease mitigation must be compared to the resource costs, guiding decisions made with the objective of achieving the optimal net outcome.</p> <p>Discussion</p> <p>Economics provides criteria to guide decisions aimed at optimising the net benefits from the use of scarce resources. Assessing the benefits of disease mitigation is no exception. However, the technical complexity of mitigation means that economic evaluation is not straightforward because of the technical relationship of surveillance to intervention. We argue that analysis of the magnitudes and distribution of benefits and costs for any given strategy, and hence the outcome in net terms, requires that mitigation is considered in three conceptually distinct stages. In Stage I, 'sustainment', the mitigation objective is to sustain a free or acceptable status by preventing an increase of a pathogen or eliminating it when it occurs. The role of surveillance is to document that the pathogen remains below a defined threshold, giving early warning of an increase in incidence or other significant changes in risk, and enabling early response. If a pathogen is not contained, the situation needs to be assessed as Stage II, 'investigation'. Here, surveillance obtains critical epidemiological information to decide on the appropriate intervention strategy to reduce or eradicate a disease in Stage III, 'implementation'. Stage III surveillance informs the choice, timing, and scale of interventions and documents the progress of interventions directed at prevalence reduction in the population.</p> <p>Summary</p> <p>This article originates from a research project to develop a conceptual framework and practical tool for the economic evaluation of surveillance. Exploring the technical relationship between mitigation as a source of economic value and surveillance and intervention as sources of economic cost is crucial. A framework linking the key technical relationships is proposed. Three conceptually distinct stages of mitigation are identified. Avian influenza, salmonella, and foot and mouth disease are presented to illustrate the framework.</p

Home based exercise to improve turning and mobility performance among community dwelling older adults: protocol for a randomized controlled trial

Background: Turning is a common activity for older people, and is one of the activities commonly associated with falls during walking. Falls that occur while walking and turning have also been associated with an increased risk of hip fracture in older people. Despite the importance of stability during turning, there has been little focus on identifying this impairment in at risk older people, or in evaluating interventions aiming to improve this outcome. This study will evaluate the effectiveness of a 16 week tailored home based exercise program in older adults aged (50 years and above) who were identified as having unsteadiness during turning.Methods/Design: A single blind randomized controlled trial will be conducted, with assessors blind to group allocation. Study participants will be aged 50 years and above, living in the community and have been identified as having impaired turning ability [outside of age and gender normal limits on the Step Quick Turn (180 degree turn) task on the Neurocom® Balance Master with long plate]. After a comprehensive baseline assessment, those classified as having balance impairment while turning will be randomized to intervention or control group. The intervention group will receive a 16 week individualized balance and strength home exercise program, based on the Otago Exercise Program with additional exercises focused on improving turning ability. Intervention group will attend four visit to the assessment centre over 16 weeks period, for provision, monitoring, modification of the exercise and encourage ongoing participation. Participants in the control group will continue with their usual activities. All participants will be re-assessed on completion of the 16 week program. Primary outcome measures will be the Step Quick Turn Test and Timed-Up and Go test. Secondary outcomes will include other clinical measures of balance, psychological aspects of falls, incidence of falls and falls risk factors. Discussion: Results of this study will provide useful information for clinicians on the types of exercises to improve turning ability in older people with increased falls risk and the effectiveness of these exercises in improving outcomes

Latitudinal patterns in stabilizing density dependence of forest communities

Numerous studies have shown reduced performance in plants that are surrounded by neighbours of the same species1, 2, a phenomenon known as conspecific negative density dependence (CNDD)3. A long-held ecological hypothesis posits that CNDD is more pronounced in tropical than in temperate forests4, 5, which increases community stabilization, species coexistence and the diversity of local tree species6, 7. Previous analyses supporting such a latitudinal gradient in CNDD8, 9 have suffered from methodological limitations related to the use of static data10–12. Here we present a comprehensive assessment of latitudinal CNDD patterns using dynamic mortality data to estimate species-site-specific CNDD across 23 sites. Averaged across species, we found that stabilizing CNDD was present at all except one site, but that average stabilizing CNDD was not stronger toward the tropics. However, in tropical tree communities, rare and intermediate abundant species experienced stronger stabilizing CNDD than did common species. This pattern was absent in temperate forests, which suggests that CNDD influences species abundances more strongly in tropical forests than it does in temperate ones13. We also found that interspecific variation in CNDD, which might attenuate its stabilizing effect on species diversity14, 15, was high but not significantly different across latitudes. Although the consequences of these patterns for latitudinal diversity gradients are difficult to evaluate, we speculate that a more effective regulation of population abundances could translate into greater stabilization of tropical tree communities and thus contribute to the high local diversity of tropical forests

Major axes of variation in tree demography across global forests

The future trajectory of global forests is closely intertwined with tree demography, and a major fundamental goal in ecology is to understand the key mechanisms governing spatio‐temporal patterns in tree population dynamics. While previous research has made substantial progress in identifying the mechanisms individually, their relative importance among forests remains unclear mainly due to practical limitations. One approach to overcome these limitations is to group mechanisms according to their shared effects on the variability of tree vital rates and quantify patterns therein. We developed a conceptual and statistical framework (variance partitioning of Bayesian multilevel models) that attributes the variability in tree growth, mortality, and recruitment to variation in species, space, and time, and their interactions – categories we refer to as organising principles (OPs). We applied the framework to data from 21 forest plots covering more than 2.9 million trees of approximately 6500 species. We found that differences among species, the species OP, proved a major source of variability in tree vital rates, explaining 28–33% of demographic variance alone, and 14–17% in interaction with space, totalling 40–43%. Our results support the hypothesis that the range of vital rates is similar across global forests. However, the average variability among species declined with species richness, indicating that diverse forests featured smaller interspecific differences in vital rates. Moreover, decomposing the variance in vital rates into the proposed OPs showed the importance of unexplained variability, which includes individual variation, in tree demography. A focus on how demographic variance is organized in forests can facilitate the construction of more targeted models with clearer expectations of which covariates might drive a vital rate. This study therefore highlights the most promising avenues for future research, both in terms of understanding the relative contributions of groups of mechanisms to forest demography and diversity, and for improving projections of forest ecosystems