Is it feasible to deliver a complex intervention to improve the outcome of falls in people with dementia? A protocol for the DIFRID feasibility study

Background: People with dementia (PWD) experience ten times as many incident falls as people without dementia. Little is known about how best to deliver services to people with dementia following a fall. We used an integrated, mixed-methods approach to develop a new intervention which combines theory generated via a realist synthesis and data on current provision and pathways, gathered through a prospective observational study as well as qualitative interviews, focus groups, and ethnographic observation. This intervention is to be tested in a feasibility study in the UK National Health Service. Methods: People living with dementia in one of three geographical areas will be eligible for the study if they experience a fall requiring healthcare attention and have an informal carer. Potential participants will be identified by community services (primary care, paramedics, telecare), secondary care (ED; facilitated discharge services; rehabilitation outreach teams) and research case registers. Participants will receive a complex multidisciplinary intervention focused on their goals and interests for up to 12 weeks. The intervention will be delivered by occupational therapists, physiotherapists and rehabilitation support workers. Feasibility outcomes will include recruitment and retention, suitability and acceptability of outcome measures and acceptability, feasibility and fidelity of intervention components. PWD outcome measures will include number of falls, Montreal Cognitive Assessment (MOCA), European Quality of Life Instrument (EQ-5D-5L), Quality of Life–Alzheimer’s Disease Scale (QOL-AD), Modified Falls Efficacy Scale (MFES) and Goal Attainment Scaling (GAS). PWD outcome measures completed by an informal carer will include Disability Assessment for Dementia (DAD), EQ-5D-5L Proxy, QoL-AD Proxy and a Health Utilisation Questionnaire (HUQ), The carer outcome measure will be the Zarit Burden Interview (ZBI). An embedded process evaluation will explore barriers and facilitators to recruitment and intervention delivery. Discussion: The study results will inform whether and how a larger multicentre RCT should be undertaken. A full RCT would have the potential to show how outcomes can be improved for people with dementia who have fallen. Ethics and dissemination: The National Research Ethics Service Committee Newcastle and North Tyneside 2 approved the feasibility study. Trial registration: International Standard Randomised Controlled Trial Registry Registration number: ISRCTN41760734 Date of registration: 16/11/201

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression

Age-associated decline in muscle function represents a significant public health burden. Vitamin D-deficiency is also prevalent in aging subjects, and has been linked to loss of muscle mass and strength (sarcopenia), but the precise role of specific vitamin D metabolites in determining muscle phenotype and function is still unclear. To address this we quantified serum concentrations of multiple vitamin D metabolites, and assessed the impact of these metabolites on body composition/muscle function parameters, and muscle biopsy gene expression in a retrospective study of a cohort of healthy volunteers. Active serum 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3), but not inactive 25-hydroxyvitamin D3 (25OHD3), correlated positively with measures of lower limb strength including power (rho = 0.42, p = 0.02), velocity (Vmax, rho = 0.40, p = 0.02) and jump height (rho = 0.36, p = 0.04). Lean mass correlated positively with 1α,25(OH)2D3 (rho = 0.47, p = 0.02), in women. Serum 25OHD3 and inactive 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) had an inverse relationship with body fat (rho = -0.30, p = 0.02 and rho = -0.33, p = 0.01, respectively). Serum 25OHD3 and 24,25(OH)2D3 were also correlated with urinary steroid metabolites, suggesting a link with glucocorticoid metabolism. PCR array analysis of 92 muscle genes identified vitamin D receptor (VDR) mRNA in all muscle biopsies, with this expression being negatively correlated with serum 25OHD3, and Vmax, and positively correlated with fat mass. Of the other 91 muscle genes analysed by PCR array, 24 were positively correlated with 25OHD3, but only 4 were correlated with active 1α,25(OH)2D3. These data show that although 25OHD3 has potent actions on muscle gene expression, the circulating concentrations of this metabolite are more closely linked to body fat mass, suggesting that 25OHD3 can influence muscle function via indirect effects on adipose tissue. By contrast, serum 1α,25(OH)2D3 has limited effects on muscle gene expression, but is associated with increased muscle strength and lean mass in women. These pleiotropic effects of the vitamin D ‘metabolome’ on muscle function indicate that future supplementation studies should not be restricted to conventional analysis of the major circulating form of vitamin D, 25OHD3

Integrative network analysis identified key genes and pathways in the progression of hepatitis C virus induced hepatocellular carcinoma

Background: Incidence of hepatitis C virus (HCV) induced hepatocellular carcinoma (HCC) has been increasing in the United States and Europe during recent years. Although HCV-associated HCC shares many pathological characteristics with other types of HCC, its molecular mechanisms of progression remain elusive. Methods: To investigate the underlying pathology, we developed a systematic approach to identify deregulated biological networks in HCC by integrating gene expression profiles with high-throughput protein-protein interaction data. We examined five stages including normal (control) liver, cirrhotic liver, dysplasia, early HCC and advanced HCC. Results: Among the five consecutive pathological stages, we identified four networks including precancerous networks (Normal-Cirrhosis and Cirrhosis-Dysplasia) and cancerous networks (Dysplasia-Early HCC, Early-Advanced HCC). We found little overlap between precancerous and cancerous networks, opposite to a substantial overlap within precancerous or cancerous networks. We further found that the hub proteins interacted with HCV proteins, suggesting direct interventions of these networks by the virus. The functional annotation of each network demonstrates a high degree of consistency with current knowledge in HCC. By assembling these functions into a module map, we could depict the stepwise biological functions that are deregulated in HCV-induced hepatocarcinogenesis. Additionally, these networks enable us to identify important genes and pathways by developmental stage, such as LCK signalling pathways in cirrhosis, MMP genes and TIMP genes in dysplastic liver, and CDC2-mediated cell cycle signalling in early and advanced HCC. CDC2 (alternative symbol CDK1), a cell cycle regulatory gene, is particularly interesting due to its topological position in temporally deregulated networks. Conclusions: Our study uncovers a temporal spectrum of functional deregulation and prioritizes key genes and pathways in the progression of HCV induced HCC. These findings present a wealth of information for further investigation

Proteoglycans and osteolysis.

Osteolysis is a complex mechanism resulting from an exacerbated activity of osteoclasts associated or not with a dysregulation of osteoblast metabolism leading to bone loss. This bone defect is not compensated by bone apposition or by apposition of bone matrix with poor mechanical quality. Osteolytic process is regulated by mechanical constraints, by polypeptides including cytokines and hormones, and by extracellular matrix components such as proteoglycans (PGs) and glycosaminoglycans (GAGs). Several studies revealed that GAGs may influence osteoclastogenesis, but data are very controversial: some studies showed a repressive effect of GAGs on osteoclastic differentiation, whereas others described a stimulatory effect. The controversy also affects osteoblasts which appear sometimes inhibited by polysaccharides and sometimes stimulated by these compounds. Furthermore, long-term treatment with heparin leads to the development of osteoporosis fueling the controversy. After a brief description of the principal osteoclastogenesis assays, the present chapter summarizes the main data published on the effect of PGs/GAGs on bone cells and their functional incidence on osteolysis

Dancing in time: feasibility and acceptability of a contemporary dance programme to modify risk factors for falling in community dwelling older adults

Background: Falls are a common cause of injury in older adults, with the prevention of falls being a priority for public health departments around the world. This study investigated the feasibility, and impact of an 8 week contemporary dance programme on modifiable physical (physical activity status, mobility, sedentary behaviour patterns) and psychosocial (depressive state, fear of falling) risk factors for falls. Methods: An uncontrolled ‘pre-post’ intervention design was used. Three groups of older (60 yrs.+) adults were recruited from local community groups to participate in a 3 separate, 8 week dance programmes. Each programme comprised two, 90 min dance classes per week. Quantitative measures of physical activity, sedentary behaviour, depression, mobility and fear of falling were measured at baseline (T1) and after 8 weeks of dance (T2). Weekly attendance was noted, and post-study qualitative work was conducted with participants in 3 separate focus groups. A combined thematic analysis of these data was conducted. Results: Of the 38 (Mean Age = 77.3 ± 8.4 yrs., 37 females) who attended the dance sessions, 22 (21 females; 1 male; mean age = 74.8, ±8.44) consented to be part of the study. Mean attendance was 14.6 (±2.6) sessions, and mean adherence was 84.3% (±17). Significant increases in moderate and vigorous physical activity were noted, with a significant decrease in sitting time over the weekdays (p < 0.05). Statistically significant decreases in the mean Geriatric Depression Scale (p < 0.05) and fear of falling (p < 0.005) score were noted, and the time taken to complete the TUG test decreased significantly from 10.1 s to 7.7 s over the 8 weeks (p < 0.005). Themes from the focus groups included the dance programme as a means of being active, health Benefits, and dance-related barriers and facilitators. Conclusions: The recruitment of older adults, good adherence and favourability across all three sites indicate that a dance programme is feasible as an intervention, but this may be limited to females only. Contemporary dance has the potential to positively affect the physical activity, sitting behaviour, falls related efficacy, mobility and incidence of depression in older females which could reduce their incidence of falls. An adequately powered study with control groups are required to test this intervention further

Risk factors for incident falls in older men and women:The English longitudinal study of ageing

Background: falls are a major cause of disability and death in older people, particularly women. Cross-sectional surveys suggest that some risk factors associated with a history of falls may be sex-specific, but whether risk factors for incident falls differ between the sexes is unclear. We investigated whether risk factors for incident falls differ between men and women.Methods: participants were 3298 people aged ≥60 who took part in the Waves 4-6 surveys of the English Longitudinal Study of Ageing. At Wave 4, they provided information about sociodemographic, lifestyle, behavioural and medical factors and had their physical and cognitive function assessed. Data on incident falls during the four-year follow-up period was collected from them at Waves 5 and 6. Poisson regression with robust variance estimation was used to derive relative risks (RR) for the association between baseline characteristics and incident falls.Results: in multivariable-adjusted models that also controlled for history of falls, older age was the only factor associated with increased risk of incident falls in both sexes. Some factors were only predictive of falls in one sex, namely more depressive symptoms (RR (95% CI) 1.03 (1.01,1.06)), incontinence (1.12 (1.00,1.24)) and never having married in women (1.26 (1.03,1.53)), and greater comorbidity (1.04 (1.00,1.08)), higher levels of pain (1.10 (1.04,1.17) and poorer balance, as indicated by inability to attempt a full-tandem stand, (1.23 (1.04,1.47)) in men. Of these, only the relationships between pain, balance and comorbidity and falls risk differed significantly by sex.Conclusions: there were some differences between the sexes in risk factors for incident falls. Our observation that associations between pain, balance and comorbidity and incident falls risk varied by sex needs further investigation in other cohorts. <br/

Effectiveness of interventions aimed at improving physical and psychological outcomes of fall-related injuries in people with dementia: a narrative systematic review

Background: The annual prevalence of falls in people with dementia ranges from 47 to 90%. Falls are a common reason for hospital admission in people with dementia, and there is limited research evidence regarding the care pathways experienced by this population. In addition to immediate management of an injury, prevention of further falls is likely to be an important part of any successful intervention. This review aims to assess the effectiveness of interventions for improving the physical and psychological wellbeing of people with dementia who have sustained a fall-related injury. Methods: Systematic review methodologies were employed utilising searches across multiple databases (MEDLINE, CENTRAL, Health Management Information Consortium, EMBASE, CINAHL, Web of Science, Allied and Complementary Medicine Database, and Physiotherapy Evidence Database (PEDro)) and citation chaining. Studies including people with a known diagnosis of dementia living in the community and who present at health services with a fall, with or without injury, were included. Outcomes of interest included mobility, recurrent falls, activities of daily living, length of hospital stay, and post-discharge residence. Results were independently reviewed and quality assessed by two researchers, and data extracted using a customised form. A narrative synthesis was performed due to heterogeneity of the included studies. Results: Seven studies were included. Interventions clustered into three broad categories: multidisciplinary in-hospital post-surgical geriatric assessment; pharmaceuticals; and multifactorial assessment. Multidisciplinary care and early mobilisation showed short-term improvements for some outcomes. Only an annual administration of zoledronic acid showed long-term reduction in recurrent falls. Conclusions: Due to high heterogeneity across the studies, definitive conclusions could not be reached. Most post-fall interventions were not aimed at patients with dementia and have shown little efficacy regardless of cognitive status. Minor improvements to some quality of life indicators were shown, but these were generally not statistically significant. Conclusions were also limited due to most studies addressing hip fracture; the interventions provided for this type of injury may not be suitable for other types of fractures or soft tissue injuries, or for use in primary care