Long-term in-vitro precision of direct digital X-ray radiogrammetry

Digital X-ray radiogrammetry (DXR) calculates peripheral bone mineral density (BMD) from hand radiographs. The short-term precision for direct DXR has been reported to be highly satisfactory. However, long-term precision for this method has not been examined. Thus, the aim of this study was to examine the long-term in-vitro precision for the new direct digital version of DXR. The in-vitro precision for direct DXR was tested with cadaver phantoms on four different X-ray systems at baseline, 3 months, 6 months, and in one machine also at 12 months. At each time point, 31 measurements were performed. The in-vitro longitudinal precision for the four radiographic systems ranged from 0.22 to 0.43% expressed as coefficient of variation (CV%). The smallest detectable difference (SDD) ranged from 0.0034 to 0.0054 g/cm(2). The in vitro long-term precision for direct DXR was comparable to the previous reported short-term in-vitro precision for all tested X-ray systems. These data show that DXR is a stable method for detecting small changes in bone density during 6-12 months of follow-up

ChIPseqR: analysis of ChIP-seq experiments

<p>Abstract</p> <p>Background</p> <p>The use of high-throughput sequencing in combination with chromatin immunoprecipitation (ChIP-seq) has enabled the study of genome-wide protein binding at high resolution. While the amount of data generated from such experiments is steadily increasing, the methods available for their analysis remain limited. Although several algorithms for the analysis of ChIP-seq data have been published they focus almost exclusively on transcription factor studies and are usually not well suited for the analysis of other types of experiments.</p> <p>Results</p> <p>Here we present ChIPseqR, an algorithm for the analysis of nucleosome positioning and histone modification ChIP-seq experiments. The performance of this novel method is studied on short read sequencing data of <it>Arabidopsis thaliana </it>mononucleosomes as well as on simulated data.</p> <p>Conclusions</p> <p>ChIPseqR is shown to improve sensitivity and spatial resolution over existing methods while maintaining high specificity. Further analysis of predicted nucleosomes reveals characteristic patterns in nucleosome sequences and placement.</p

The Coiled Coils of Cohesin Are Conserved in Animals, but Not In Yeast

The SMC proteins are involved in DNA repair, chromosome condensation, and sister chromatid cohesion throughout Eukaryota. Long, anti-parallel coiled coils are a prominent feature of SMC proteins, and are thought to serve as spacer rods to provide an elongated structure and to separate domains. We reported recently that the coiled coils of mammalian condensin (SMC2/4) showed moderate sequence divergence (approximately 10-15%) consistent with their functioning as spacer rods. The coiled coils of mammalian cohesins (SMC1/3), however, were very highly constrained, with amino acid sequence divergence typically <0.5%. These coiled coils are among the most highly conserved mammalian proteins, suggesting that they make extensive contacts over their entire surface.Here, we broaden our initial analysis of condensin and cohesin to include additional vertebrate and invertebrate organisms and multiple species of yeast. We found that the coiled coils of SMC1/3 are highly constrained in Drosophila and other insects, and more generally across all animal species. However, in yeast they are no more constrained than the coils of SMC2/4 and Ndc80/Nuf2p, suggesting that they are serving primarily as spacer rods.SMC1/3 functions for sister chromatid cohesion in all species. Since its coiled coils apparently serve only as spacer rods in yeast, it is likely that this is sufficient for sister chromatid cohesion in all species. This suggests an additional function in animals that constrains the sequence of the coiled coils. Several recent studies have demonstrated that cohesin has a role in gene expression in post-mitotic neurons of Drosophila, and other animal cells. Some variants of human Cornelia de Lange Syndrome involve mutations in human SMC1/3. We suggest that the role of cohesin in gene expression may involve intimate contact of the coiled coils of SMC1/3, and impose the constraint on sequence divergence

CCN2/Connective Tissue Growth Factor Is Essential for Pericyte Adhesion and Endothelial Basement Membrane Formation during Angiogenesis

CCN2/Connective Tissue Growth Factor (CTGF) is a matricellular protein that regulates cell adhesion, migration, and survival. CCN2 is best known for its ability to promote fibrosis by mediating the ability of transforming growth factor β (TGFβ) to induce excess extracellular matrix production. In addition to its role in pathological processes, CCN2 is required for chondrogenesis. CCN2 is also highly expressed during development in endothelial cells, suggesting a role in angiogenesis. The potential role of CCN2 in angiogenesis is unclear, however, as both pro- and anti-angiogenic effects have been reported. Here, through analysis of Ccn2-deficient mice, we show that CCN2 is required for stable association and retention of pericytes by endothelial cells. PDGF signaling and the establishment of the endothelial basement membrane are required for pericytes recruitment and retention. CCN2 induced PDGF-B expression in endothelial cells, and potentiated PDGF-B-mediated Akt signaling in mural (vascular smooth muscle/pericyte) cells. In addition, CCN2 induced the production of endothelial basement membrane components in vitro, and was required for their expression in vivo. Overall, these results highlight CCN2 as an essential mediator of vascular remodeling by regulating endothelial-pericyte interactions. Although most studies of CCN2 function have focused on effects of CCN2 overexpression on the interstitial extracellular matrix, the results presented here show that CCN2 is required for the normal production of vascular basement membranes

The theory of expanded, extended, and enhanced opportunities for youth physical activity promotion

Background Physical activity interventions targeting children and adolescents (≤18 years) often focus on complex intra- and inter-personal behavioral constructs, social-ecological frameworks, or some combination of both. Recently published meta-analytical reviews and large-scale randomized controlled trials have demonstrated that these intervention approaches have largely produced minimal or no improvements in young people\u27s physical activity levels. Discussion In this paper, we propose that the main reason for previous studies\u27 limited effects is that fundamental mechanisms that lead to change in youth physical activity have often been overlooked or misunderstood. Evidence from observational and experimental studies is presented to support the development of a new theory positing that the primary mechanisms of change in many youth physical activity interventions are approaches that fall into one of the following three categories: (a) the expansion of opportunities for youth to be active by the inclusion of a new occasion to be active, (b) the extension of an existing physical activity opportunity by increasing the amount of time allocated for that opportunity, and/or (c) the enhancement of existing physical activity opportunities through strategies designed to increase physical activity above routine practice. Their application and considerations for intervention design and interpretation are presented. Summary The utility of these mechanisms, referred to as the Theory of Expanded, Extended, and Enhanced Opportunities (TEO), is demonstrated in their parsimony, logical appeal, support with empirical evidence, and the direct and immediate application to numerous settings and contexts. The TEO offers a new way to understand youth physical activity behaviors and provides a common taxonomy by which interventionists can identify appropriate targets for interventions across different settings and contexts. We believe the formalization of the TEO concepts will propel them to the forefront in the design of future intervention studies and through their use, lead to a greater impact on youth activity behaviors than what has been demonstrated in previous studies

A mixed methods process evaluation of a person-centred falls prevention program

Background RESPOND is a telephone-based falls prevention program for older people who present to a hospital emergency department (ED) with a fall. A randomised controlled trial (RCT) found RESPOND to be effective at reducing the rate of falls and fractures, compared with usual care, but not fall injuries or hospitalisations. This process evaluation aimed to determine whether RESPOND was implemented as planned, and identify implementation barriers and facilitators. Methods A mixed-methods evaluation was conducted alongside the RCT. Evaluation participants were the RESPOND intervention group (n=263) and the clinicians delivering RESPOND (n=7). Evaluation data were collected from participant recruitment and intervention records, hospital administrative records, audio-recordings of intervention sessions, and participant questionnaires. The Rochester Participatory Decision-Making scale (RPAD) was used to evaluate person-centredness (score range 0 (worst) - 9 (best)). Process factors were compared with pre-specified criteria to determine implementation fidelity. Six focus groups were held with participants (n=41), and interviews were conducted with RESPOND clinicians (n=6). Quantitative data were analysed descriptively and qualitative data thematically. Barriers and facilitators to implementation were mapped to the ‘Capability, Opportunity, Motivation – Behaviour’ (COM-B) behaviour change framework. Results RESPOND was implemented at a lower dose than the planned 10 hours over six months, with a median (IQR) of 2.9 hours (2.1, 4). The majority (76%) of participants received their first intervention session within one month of hospital discharge. Clinicians delivered the program in a person-centred manner with a median (IQR) RPAD score of 7 (6.5, 7.5) and 87% of questionnaire respondents were satisfied with the program. The reports from participants and clinicians suggested that implementation was facilitated by the use of positive and personally relevant health messages. Complex health and social issues were the main barriers to implementation. Conclusions RESPOND was person-centred and reduced falls and fractures at a substantially lower dose, using fewer resources, than anticipated. However, the low dose delivered may account for the lack of effect on falls injuries and hospitalisations. The results from this evaluation provide detailed information to guide future implementation of RESPOND of similar programs. Trial registration: This study was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614000336684 (27 March 2014)