Meta-analysis of gene-based genome-wide association studies of bone mineral density in Chinese and European subjects

Summary Gene-based association approach could be regarded as a complementary analysis to the single SNP association analysis. We meta-analyzed the findings from the gene-based association approach using the genome-wide association studies (GWAS) data from Chinese and European subjects, confirmed several well established bone mineral density (BMD) genes, and suggested several novel BMD genes. Introduction The introduction of GWAS has greatly increased the number of genes that are known to be associated with common diseases. Nonetheless, such a single SNP GWAS has a lower power to detect genes with multiple causal variants. We aimed to assess the association of each gene with BMD variation at the spine and hip using gene-based GWAS approach. Methods We studied 778 Hong Kong Southern Chinese (HKSC) women and 5,858 Northern Europeans (dCG); age, sex, and weight were adjusted in the model. The main outcome measure was BMD at the spine and hip. Results Nine genes showed suggestive p value in HKSC, while 4 and 17 genes showed significant and suggestive p values respectively in dCG. Meta-analysis using weighted Z-transformed test confirmed several known BMD genes and suggested some novel ones at 1q21.3, 9q22, 9q33.2, 20p13, and 20q12. Top BMD genes were significantly associated with connective tissue, skeletal, and muscular system development and function (p<0.05). Gene network inference revealed that a large number of these genes were significantly connected with each other to form a functional gene network, and several signaling pathways were strongly connected with these gene networks. Conclusion Our gene-based GWAS confirmed several BMD genes and suggested several novel BMD genes. Genetic contribution to BMD variation may operate through multiple genes identified in this study in functional gene networks. This finding may be useful in identifying and prioritizing candidate genes/loci for further study. © International Osteoporosis Foundation and National Osteoporosis Foundation 2011.published_or_final_versionSpringer Open Choice, 21 Feb 201

Transitioning to Multiple-use Polyculture Grassland-derived Bioenergy Feedstock Systems

We argue that research and development of grassland-derived bioenergy feedstock (GBF) has focused unduly on dedicated monospecific biomass systems to the detriment of more stable multiple-use multispecies grasslands. This has retarded GBF adoption as a viable, sustainable contribution to renewable energy production in North America. We hypothesize that focusing on multiple-use GBFs will foster greater feedstock availability for nascent renewable energy generation while minimizing financial risk to grassland husbandry during market transitions from current grazing systems to more flexible business models. Our hypothesis is that source and demand are more likely to develop simultaneously under less risky multiple-use grassland management. We review what little research exists detailing such multiple-use systems that include GBF as a major component. We propose that more federal and private sector research funding should focus on perennial forage legumes and bunchgrasses for multiple uses including forage, bioenergy, grassland restoration, wildlife, and ecosystems services such as hydrology, carbon capture and biodiversity. These data cover both native and introduced species in cultivated pastures as well as managed rangeland and native grassland. We conclude that more research effort should be focused on multiple-use GBF in order to identify individual species, mixtures and ecosystems that provide flexibility in the face of unpredictable grassland environments and volatile energy markets

Ethnic difference of clinical vertebral fracture risk

Vertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. This study observed that Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians, but the vertebral fracture rates were higher, resulting in a high vertebral-to-hip fracture ratio. As a result, estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate. Introduction: Vertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. The aim of this study was to report the incidence of clinical vertebral fractures among the Chinese and to compare the vertebral-to-hip fracture risk to other ethnic groups. Methods: Four thousand, three hundred eighty-six community-dwelling Southern Chinese subjects (2,302 women and 1,810 men) aged 50 or above were recruited in the Hong Kong Osteoporosis Study since 1995. Baseline demographic characteristics and medical history were obtained. Subjects were followed annually for fracture outcomes with a structured questionnaire and verified by the computerized patient information system of the Hospital Authority of the Hong Kong Government. Only non-traumatic incident hip fractures and clinical vertebral fractures that received medical attention were included in the analysis. The incidence rates of clinical vertebral fractures and hip fractures were determined and compared to the published data of Swedish Caucasian and Japanese populations. Results: The mean age at baseline was 62 ± 8.2 years for women and 68 ± 10.3 years for men. The average duration of follow-up was 4.0 ± 2.8 (range, 1 to 14) years for a total of 14,733 person-years for the whole cohort. The incidence rate for vertebral fracture was 194/100,000 person-years in men and 508/100,000 person-years in women, respectively. For subjects above the age of 65, the clinical vertebral fracture and hip fracture rates were 299/100,000 and 332/100,000 person-years, respectively, in men, and 594/100,000 and 379/100,000 person-years, respectively, in women. Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians. At the age of 65 or above, the hip fracture rates for Asian (Hong Kong Chinese and Japanese) men and women were less than half of that in Caucasians, but the vertebral fracture rate was higher in Asians, resulting in a high vertebral-to-hip fracture ratio. Conclusions: The incidences of vertebral and hip fractures, as well as the vertebral-to-hip fracture ratios vary in Asians and Caucasians. Estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Singular regional brightening events on Titan as seen by Cassini/VIMS

Titan, the largest satellite of Saturn, is the only satellite in the solar system with a dense atmosphere. The close and continuous observations of Titan by the Cassini spacecraft, in orbit around Saturn since July 2004, bring us evidences that Titan tropo-sphere and low stratosphere experience an exotic, but complete meteorological cycle similar to the Earth hy-drological cycle, with hydrocarbons evaporation, con-densation in clouds, and rainfall. Cassini monitoring campaigns also demonstrate that Titan’s cloud cover-age and climate vary with latitude. Titan’s tropics, with globally weak meteorological activity and widespread dune fields, seem to be slightly more arid than the poles, where extensive and numerous liquid reservoirs and sustained cloud activity were discovered. Only a few tropospheric clouds have been observed at Titan’s tropics during the southern summer [2-4]. As equinox was approaching (in August 2009), they oc-curred more frequently and appeared to grow in strength and size [5-7]

Foreign policy beliefs and support for Stephen Harper and the Conservative Party

Similar to other recent Canadian elections, foreign policy did not feature prominently in the 2011 federal election campaign. In fact, many doubt Canadian public opinion on international affairs is linked to the actions taken by recent Governments. In this paper, we examine Canadian public opinion toward a range of foreign policy issues and argue that the survey questions measure two latent dimensions —militarism and internationalism. Our survey evidence indicates the existence of an “issue public” which is prepared to endorse military action and is skeptical of human rights and overseas aid programs, and this group is far more supportive of Prime Minister Harper and the Conservative Party than other Canadians. The absence of an elite discussion, either among politicians or between media elites, about the direction of Canadian foreign policy does not prevent the Canadian voter from thinking coherently about questions pertaining to this issue domain and employing these beliefs to support or oppose political parties and their leaders

Bone mineral density enhances use of clinical risk factors in predicting ten-year risk of osteoporotic fractures in Chinese men: the Hong Kong Osteoporosis Study

This prospective study aimed to determine the risk factors and the 10-year probability of osteoporotic fracture in Southern Chinese men. The findings show substantial population differences in fracture incidence and risk prediction compared to the FRAX TM model, and the addition of BMD information to clinical risk factor assessment improved fracture risk prediction in Chinese men. Introduction: Clinical risk factors with or without bone mineral density (BMD) measurements are increasingly recognized as reliable predictors of fracture risk. Prospective data on fracture incidence in Asian men remain sparse. This prospective study aimed to determine the risk factors and the 10-year absolute fracture risk in Southern Chinese men. Methods: This is a part of the Hong Kong Osteoporosis Study. One thousand eight hundred ten (1,810) community-dwelling, treatment-naive men aged 50 years or above were evaluated. Baseline demographic characteristics, clinical risk factors and BMD were recorded. Ten-year risk of osteoporotic fracture was calculated using Cox proportional hazards models. Results: The mean age of subjects was 68.0 ± 10.3 years. After a mean follow-up period of 3.5±2.9 years (range 1 to 14 years), 37 incident low-trauma fractures were recorded. The incidence for all osteoporotic fractures and hip fractures was 635/100,000 and 123/100,000 person-years, respectively. The most significant predictors of osteoporotic fracture were history of fall (RR 14.5), femoral neck BMD T-score < -2.5 (RR 13.8) and history of fracture (RR 4.4). Each SD reduction in BMD was associated with a 1.8 to 2.6-fold increase in fracture risk. Subjects with seven clinical risk factors and BMD T-score of -1 had an absolute 10-year risk of osteoporotic fracture of 8.9%, but this increased to 22.7% if they also had a femoral neck BMD T-score of -2.5. Conclusions: These findings show substantial population differences in fracture incidence and risk prediction. The addition of BMD information to clinical risk factor assessment improved fracture risk prediction in Chinese men. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Clinical risk factor assessment had better discriminative ability than bone mineral density in identifying subjects with vertebral fracture

Summary: This study evaluated the characteristics of patients with vertebral fractures and examined the discriminative ability of clinical risk factors. The findings provide further insights into possible development of a simple, cost-effective scheme for fracture risk assessment using clinical risk factors to identify high-risk patients for further evaluation. Introduction: Vertebral fractures are the most common complication of osteoporosis. The aim of this study was to evaluate the characteristics of patients with vertebral fractures and to determine the discriminative ability of bone mineral density (BMD) and other clinical risk factors. Methods: Postmenopausal Southern Chinese women (2,178) enrolled in the Hong Kong Osteoporosis Study since 1995 were prospectively followed up for fracture outcome. Subjects (1,372) with lateral spine radiographs were included in this study. Baseline demographic, BMD, and clinical risk factor information were obtained from a structured questionnaire. Results: Subjects (299; 22%) had prevalent vertebral fractures. The prevalence of vertebral fractures increased with increasing age, number of clinical risk factors, and decreasing BMD. The odds of having a prevalent vertebral fracture per SD reduction in BMD after adjustment for age in Hong Kong Southern Chinese postmenopausal women was 1.5 for the lumbar spine and femoral neck. Analysis of the receiver operating characteristic curve revealed that bone mineral apparent density did not enhance fracture risk prediction. Subjects with ≥4 clinical risk factors had 2.3-fold higher odds of having a prevalent vertebral fracture while subjects with ≥4 clinical risk factors plus a low BMD (i.e., femoral neck T-score <-2.5) had 2.6-fold. Addition of BMD to clinical risk factors did not enhance the discriminative ability to identify subjects with vertebral fracture. Conclusions: Based on these findings, we recommend that screening efforts should focus on older postmenopausal women with multiple risk factors to identify women who are likely to have a prevalent vertebral fracture. © 2010 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Multiscale Modeling of Red Blood Cell Mechanics and Blood Flow in Malaria

Red blood cells (RBCs) infected by a Plasmodium parasite in malaria may lose their membrane deformability with a relative membrane stiffening more than ten-fold in comparison with healthy RBCs leading to potential capillary occlusions. Moreover, infected RBCs are able to adhere to other healthy and parasitized cells and to the vascular endothelium resulting in a substantial disruption of normal blood circulation. In the present work, we simulate infected RBCs in malaria using a multiscale RBC model based on the dissipative particle dynamics method, coupling scales at the sub-cellular level with scales at the vessel size. Our objective is to conduct a full validation of the RBC model with a diverse set of experimental data, including temperature dependence, and to identify the limitations of this purely mechanistic model. The simulated elastic deformations of parasitized RBCs match those obtained in optical-tweezers experiments for different stages of intra-erythrocytic parasite development. The rheological properties of RBCs in malaria are compared with those obtained by optical magnetic twisting cytometry and by monitoring membrane fluctuations at room, physiological, and febrile temperatures. We also study the dynamics of infected RBCs in Poiseuille flow in comparison with healthy cells and present validated bulk viscosity predictions of malaria-infected blood for a wide range of parasitemia levels (percentage of infected RBCs with respect to the total number of cells in a unit volume).United States. National Institutes of Health (Grant R01HL094270)National Science Foundation (U.S.). (Grant CBET-0852948)Singapore-MIT Alliance for Research and Technology Cente

Association of CDX1 binding site of periostin gene with bone mineral density and vertebral fracture risk

Summary Periostin (POSTN) as a regulator of osteoblast differentiation and bone formation may affect susceptibility to osteoporosis. This study suggests POSTN as a candidate gene for bone mineral density (BMD) variation and vertebral fracture risk, which could better our understanding about the genetic pathogenesis of osteoporosis and will be useful in clinic in the future. Introduction The genetic determination of osteoporosis is complex and ill-defined. Periostin (POSTN), an extracellular matrix secreted by osteoblasts and a regulator of osteoblast differentiation and bone formation, may affect susceptibility to osteoporosis. Methods We adopted a tag-single nucleotide polymorphism (SNP) based association method followed by imputationbased verification and identification of a causal variant. The association was investigated in 1,572 subjects with extremeBMD and replicated in an independent population of 2,509 subjects. BMD was measured by dual X-ray absorptiometry. Vertebral fractures were identified by assessing vertebral height from X-rays of the thoracolumbar spine. Association analyses were performed with PLINK toolset and imputation analyses with MACH software. The top imputation finding was subsequently validated by genotyping. Interactions between POSTN and another BMD-related candidate gene sclerostin (SOST) were analyzed using MDR program and validated by logistical regression analyses. The putative transcription factor binding with target sequence was confirmed by electrophoretic mobility shift assay (EMSA). Results Several SNPs of POSTN were associated with BMD or vertebral fractures. The most significant polymorphism was rs9547970, located at the -2,327bpupstream(P06.8×10-4)of POSTN. Carriers of the minor allele G per copy of rs9547970 had1.33higherriskofvertebralfracture(P00. 007). An interactive effect between POSTN and SOST upon BMD variation was suggested (P<0.01). A specific binding of CDX1 to the sequence of POSTN with the major allele A of rs9547970 but not the variant G allele was confirmed by EMSA. Conclusions Our results suggest POSTN as a candidate gene for BMD variation and vertebral fracture risk. © 2012 International Osteoporosis Foundation and National Osteoporosis Foundation.published_or_final_versionSpringer Open Choice, 28 May 201