Motor Competence in Early Childhood Is Positively Associated with Bone Strength in Late Adolescence

The onset of walking in early childhood results in exposure of the lower limb to substantial forces from weight bearing activity that ultimately contribute to adult bone strength. Relationships between gross motor score (GMS), at 18 months and bone outcomes measured at age 17 years were examined in 2327 participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Higher GMS indicated greater motor competence in weight‐bearing activities. Total hip bone mineral density (BMD) and hip cross‐sectional moment of inertia (CSMI) were assessed from dual‐energy X‐ray absorptiometry (DXA). Bone measures including cortical bone mineral content (BMC), periosteal circumference (PC), cortical thickness (CT), cortical bone area (CBA), cortical BMD (BMD(C)) and cross‐sectional moment of inertia (CSMI) were assessed by peripheral quantitative computed tomography (pQCT) at 50% distal‐proximal length. Before adjustment, GMS was associated with hip BMD, CSMI, and tibia BMC, PC, CT, CBA and CSMI (all p < 0.001) but not BMD(C) (p > 0.25). Strongest associations (standardized regression coefficients with 95% CI) were between GMS and hip BMD (0.086; 95% CI, 0.067 to 0.105) and tibia BMC (0.105; 95% CI, 0.089 to 0.121). With the exception of hip BMD, larger regression coefficients were observed in males (gender interactions all p < 0.05). Adjustment for lean mass resulted in substantial attenuation of regression coefficients, suggesting associations between impaired motor competence and subsequent bone development are partly mediated by alterations in body composition. In conclusion, impaired motor competence in childhood is associated with lower adolescent bone strength, and may represent a risk factor for subsequent osteoporosis. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR)

Changes in the expression of splicing factor transcripts and variations in alternative splicing are associated with lifespan in mice and humans

This is the final version of the article. Available from the publisher via the DOI in this record.Dysregulation of splicing factor expression and altered alternative splicing are associated with aging in humans and other species, and also with replicative senescence in cultured cells. Here, we assess whether expression changes of key splicing regulator genes and consequent effects on alternative splicing are also associated with strain longevity in old and young mice, across 6 different mouse strains with varying lifespan (A/J, NOD.B10Sn-H2(b) /J, PWD.Phj, 129S1/SvlmJ, C57BL/6J and WSB/EiJ). Splicing factor expression and changes to alternative splicing were associated with strain lifespan in spleen and to a lesser extent in muscle. These changes mainly involved hnRNP splicing inhibitor transcripts with most changes more marked in spleens of young animals from long-lived strains. Changes in spleen isoform expression were suggestive of reduced cellular senescence and retained cellular proliferative capacity in long-lived strains. Changes in muscle isoform expression were consistent with reduced pro-inflammatory signalling in longer-lived strains. Two splicing regulators, HNRNPA1 and HNRNPA2B1, were also associated with parental longevity in humans, in the InCHIANTI aging study. Splicing factors may represent a driver, mediator or early marker of lifespan in mouse, as expression differences were present in the young animals of long-lived strains. Changes to alternative splicing patterns of key senescence genes in spleen and key remodelling genes in muscle suggest that correct regulation of alternative splicing may enhance lifespan in mice. Expression of some splicing factors in humans was also associated with parental longevity, suggesting that splicing regulation may also influence lifespan in humans.The authors would like to acknowledge the Wellcome Trust (grant number WT097835MF LWH, DM), and NIH-NIA grant number AG038070 to The Jackson Laboratory for providing the funding for this study

Bone Erosion Measurement in Subjects with Rheumatoid Arthritis Using Magnetic Resonance Imaging

Rheumatoid arthritis (RA) is a systemic disease that can affect the nervous system, lungs, heart, skin, reticuloendothelium and joints. Currently, the gold-standard measurement for tracking the progression of the disease involves a semi-quantitative assessment of bone erosion, bone marrow edema and synovitis, as seen in magnetic resonance (MR) images, by a musculoskeletal radiologist. The work presented in this thesis identifies how computer automation can be used to quantify bone erosion volumes in MR images without a radiologists' expert and time consuming intervention. A new semi-automated hybrid segmentation algorithm that combines two established techniques: region growing and level-set segmentation, is described and evaluated for use in a clinical setting. A total of 40 participants with RA were scanned using a 1-Tesla peripheral MR scanner. Eight of the participant scans were used to train the algorithm with the remaining used to determine the accuracy, precision, and speed of the technique. The reproducibility of the hybrid algorithm and that of manual segmentation were defined in terms of intra-class correlation coefficients (ICCs). Both techniques were equally precise with ICC values greater than 0.9. According to a least squares fit between erosion volumes obtained by the hybrid algorithm with those obtained from manual tracings drawn by a radiologist, the former was found to be highly accurate ( m=1.030, b=1.385: r-squared=0.923). The hybrid algorithm was significantly faster than manual segmentation, which took two to four times longer to complete. In conclusion, computer automation shows promise as a means to quantitatively assess bone erosion volumes. The new hybrid segmentation algorithm described in this thesis could be used in a clinical setting to track the progression of RA and to evaluate the effectiveness of treatment.Doctor of Philosophy (PhD

Are We There Yet? : Reflections on the Success of the Environment Law Movement in Ontario

In this short article, the author explores the history of the environmental law movement in Canada and explains how this history has affected many of the environmental laws and trends today. With a focus on Ontario, the author reports back from a round table discussion held in Toronto in early 2008. Some of Canada\u27s leading environmental lawyers, as well as many of the pioneers of the environmental law movement, reflected at the round table on the extent to which their aspirations for strong, effective environmental laws have been met and how much more remains to be done. While we are not there yet, much has been accomplished. More importantly, a new generation of environmental lawyers has taken up the challenge of those early pioneers, and promises to advocate for environmental laws and policies that will ensure a safe and healthy environment for future generations

Are We There Yet? : Reflections on the Success of the Environment Law Movement in Ontario

In this short article, the author explores the history of the environmental law movement in Canada and explains how this history has affected many of the environmental laws and trends today. With a focus on Ontario, the author reports back from a round table discussion held in Toronto in early 2008. Some of Canada\u27s leading environmental lawyers, as well as many of the pioneers of the environmental law movement, reflected at the round table on the extent to which their aspirations for strong, effective environmental laws have been met and how much more remains to be done. While we are not there yet, much has been accomplished. More importantly, a new generation of environmental lawyers has taken up the challenge of those early pioneers, and promises to advocate for environmental laws and policies that will ensure a safe and healthy environment for future generations

The Greening of Environmental Law

Environmental law in Canada has moved through three distinct stages. The first, beginning with the passage of the early environmental protection statutes, is described as symbolic regulation. Regulation, because these laws did purport to regulate activities that had deleterious effects on the natural environment, and symbolic because the level and degree of regulation was largely symbolic. By the mid \u2770s and early \u2780s these laws had given way to two complementary developments. The first involved the introduction of environmental assessment (or audit) statutes and procedures; the second involved a strengthening and expanding of the traditional regulatory tools. The clear thrust of this period was preventive or how to anticipate and avoid potential environmental problems before they arose. Neither symbolic regulation nor preventive regulation have been particularly successful in avoiding or remedying pollution problems, however. The approaches either proceed from a wrong premise about the nature of the problem (market or technological failure) or assume that the solution lies in a process that is highly adversarial and hence time-consuming, expensive and unlikely to generate creative solutions to difficult problems. Growing recognition of these deficiencies has led to a third, greener stage of environmental regulation: co-operative problem-solving. The premise behind this approach is that all of society shares the problem of environmental degradation and hence all of society must work together to solve the problem. This new and emerging stage of regulation is not without its problems, but it clearly offers the promise of harnessing the creative energies of all sectors of society to build co-operative solutions to environmental problems