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AIMS: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations. METHODS AND RESULTS: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS. CONCLUSION: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.

BACKGROUND: Extravasation injury remains a significant preventable cause of morbidity and mortality in neonates. Equipping nursing students with the requisite knowledge and skills is essential for appropriate prevention, early detection, and management of extravasation injury. OBJECTIVES: To develop a technology-enhanced, enquiry-based learning program for nursing students on the prevention and management of neonatal extravasation injury and examine its impact on their knowledge, approaches to studying and experience of learning. DESIGN: A pre-test/post-test study with qualitative evaluation. SETTINGS: Two university pre-registration nursing programs in Hong Kong. PARTICIPANTS: A total of 192 senior-year nursing students. METHODS: A novel learning program was developed comprising 25 scenario-based video vignettes supplemented with critical-thinking exercises, discussion guides, interactive games, reading materials and a 3-hour in-class interactive workshop. Students received unlimited online access to the program. Data were collected at baseline and one-month post-workshop. Outcomes were students' level of knowledge of prevention and management of extravasation injuries and related care, approaches to studying, and experience of learning. Paired t-tests were performed on pre- post-test outcome data and individual semi-structured interviews were conducted at one-month post-workshop, transcribed verbatim and analyzed thematically. RESULTS: There were statistically significant improvements in students' level of knowledge and use of a deep approach to learning at one month compared with baseline. Students were highly satisfied with the program, appreciating the video vignettes and interactive small group discussions with academics and clinicians. Suggestions for enhancing the program included more time for the workshop, interaction with clinicians, and details on the administration of neonatal medications and dosages. CONCLUSIONS: This study showed that a novel technolo

Quantitative MS of human plasma lipids is a promising technology for translation into clinical applications. Current MS-based lipidomic methods rely on either direct infusion (DI) or chromatographic lipid separation methods (including reversed phase and hydrophilic interaction LC). However, the use of lipid markers in laboratory medicine is limited by the lack of reference values, largely because of considerable differences in the concentrations measured by different laboratories worldwide. These inconsistencies can be explained by the use of different sample preparation protocols, method-specific calibration procedures, and other experimental and data-reporting parameters, even when using identical starting materials. Here, we systematically investigated the roles of some of these variables in multiple approaches to lipid analysis of plasma samples from healthy adults by considering: 1) different sample introduction methods (separation vs. DI methods); 2) different MS instruments; and 3) between-laboratory differences in comparable analytical platforms. Each of these experimental variables resulted in different quantitative results, even with the inclusion of isotope-labeled internal standards for individual lipid classes. We demonstrated that appropriate normalization to commonly available reference samples (i.e., "shared references") can largely correct for these systematic method-specific quantitative biases. Thus, to harmonize data in the field of lipidomics, in-house long-term references should be complemented by a commonly available shared reference sample, such as NIST SRM 1950, in the case of human plasma.

Recent genome-wide association studies (GWAS) have identified multiple loci associated with coronary artery disease (CAD) among predominantly Europeans. However, their relevance to multi-ethnic populations from Southeast Asia is largely unknown. We performed a meta-analysis of four GWAS comprising three Chinese studies and one Malay study (Total N = 2,169 CAD cases and 7,376 controls). Top hits (P < 5 × 10-8) were further evaluated in 291 CAD cases and 1,848 controls of Asian Indians. Using all datasets, we validated recently identified loci associated with CAD. The involvement of known canonical pathways in CAD was tested by Ingenuity Pathway Analysis. We identified a missense SNP (rs2075291, G > T, G185C) in APOA5 for CAD that reached robust genome-wide significance (Meta P = 7.09 × 10-10, OR = 1.636). Conditional probability analysis indicated that the association at rs2075291 was independent of previously reported index SNP rs964184 in APOA5. We further replicated 10 loci previously identified among predominantly Europeans (P: 1.33 × 10-7-0.047). Seven pathways (P: 1.10 × 10-5-0.019) were identified. We identified a missense SNP, rs2075291, in APOA5 associated with CAD at a genome-wide significance level and provided new insights into pathways contributing to the susceptibility to CAD in the multi-ethnic populations from Southeast Asia.

VHA s Family Caregiver Program is designed to provide support and services to family caregivers of post-9/11 veterans who have a serious injury incurred or aggravated in the line of duty. The program provides approved primary family caregivers with a monthly financial stipend as well as training and other support services, such as counseling and respite care., Report to Congressional Requesters

Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. OBJECTIVE: High body mass index (BMI) is associated with increased risk of osteoarthritis (OA) and reduced risk of fragility fracture. However, the relationship between fragility fracture and OA remained unclear. This study sought to investigate the effect of bone mineral density (BMD) in the OA-fracture relationship.METHODS: Data from 2412 women and 1452 men aged >45 years in the Dubbo Osteoporosis Epidemiology Study (DOES) were analyzed. Individuals have been followed for up to 22 years (median: 7.5 years; range: 0.1-22 years). Femoral neck BMD (FNBMD) and lumbar spine BMD (LSBMD) was measured by dual energy X-ray absorptiometry (DXA) (GE LUNAR, Madison, WI). The presence of OA was ascertained at baseline by self-reported diagnosis. The incidence of low-trauma fracture was ascertained from X-ray reports.RESULTS: Overall, 29% of women and 26% of men had reported a diagnosis of OA. Fracture risk was significantly higher in women with OA than those without OA (Hazard ratio (HR) = 1.50; 95% confidence interval (CI), 1.28-1.76). However, the association was mainly observed in women with osteopenic BMD (HR = 1.74; 95% CI, 1.38-2.17) and normal-BMD (HR = 1.50; 95% CI, 1.06-2.13) and not in those with osteoporosis. Further analysis revealed that osteopenic women with OA had significant increase in risk of vertebral (HR = 1.85; 95% CI, 1.24-2.75) and limb fracture (HR = 2.49; 95% CI, 1.77-3.48), but not in hip fracture. In men, no comparable relationship was found before and after adjustment for covariates.CONCLUSION: Women with OA have an increased risk of fragility fracture, and the risk was mainly observed in non-osteoporotic group.

© 2014 American Society for Bone and Mineral Research. The relationship between body mass index (BMI) and fracture risk is controversial. We sought to investigate the effect of collinearity between BMI and bone mineral density (BMD) on fracture risk, and to estimate the direct and indirect effect of BMI on fracture with BMD being the mediator. The study involved 2199 women and 1351 men aged 60 years or older. BMI was derived from baseline weight and height. Femoral neck BMD was measured by dual-energy X-ray absorptiometry (DXA; GE-LUNAR, Madison, WI, USA). The incidence of fragility fracture was ascertained by X-ray reports from 1991 through 2012. Causal mediation analysis was used to assess the mediated effect of BMD on the BMI-fracture relationship. Overall, 774 women (35% of total women) and 258 men (19%) had sustained a fracture. Approximately 21% of women and 20% of men were considered obese (BMI ≥ 30). In univariate analysis, greater BMI was associated with reduced fracture risk in women (hazard ratio [HR] 0.92; 95% confidence interval [CI], 0.85 to 0.99) and in men (HR 0.77; 95% CI, 0.67 to 0.88). After adjusting for femoral neck BMD, higher BMI was associated with greater risk of fracture in women (HR 1.21; 95% CI, 1.11 to 1.31) but not in men (HR 0.96; 95% CI, 0.83 to 1.11). Collinearity had minimal impact on the BMD-adjusted results (variance inflation factor [VIF]=1.2 for men and women). However, in mediation analysis, it was found that the majority of BMI effect on fracture risk was mediated by femoral neck BMD. The overall mediated effect estimates were -0.048 (95% CI, -0.059 to -0.036; p<0.001) in women and -0.030 (95% CI, -0.042 to -0.018; p<0.001) in men. These analyses suggest that there is no significant direct effect of BMI on fracture, and that the observed association between BMI and fracture risk is mediated by femoral neck BMD in both men and women.

© 2014 American Society for Bone and Mineral Research. The relationship between body mass index (BMI) and fracture risk is controversial. We sought to investigate the effect of collinearity between BMI and bone mineral density (BMD) on fracture risk, and to estimate the direct and indirect effect of BMI on fracture with BMD being the mediator. The study involved 2199 women and 1351 men aged 60 years or older. BMI was derived from baseline weight and height. Femoral neck BMD was measured by dual-energy X-ray absorptiometry (DXA; GE-LUNAR, Madison, WI, USA). The incidence of fragility fracture was ascertained by X-ray reports from 1991 through 2012. Causal mediation analysis was used to assess the mediated effect of BMD on the BMI-fracture relationship. Overall, 774 women (35% of total women) and 258 men (19%) had sustained a fracture. Approximately 21% of women and 20% of men were considered obese (BMI ≥ 30). In univariate analysis, greater BMI was associated with reduced fracture risk in women (hazard ratio [HR] 0.92; 95% confidence interval [CI], 0.85 to 0.99) and in men (HR 0.77; 95% CI, 0.67 to 0.88). After adjusting for femoral neck BMD, higher BMI was associated with greater risk of fracture in women (HR 1.21; 95% CI, 1.11 to 1.31) but not in men (HR 0.96; 95% CI, 0.83 to 1.11). Collinearity had minimal impact on the BMD-adjusted results (variance inflation factor [VIF]=1.2 for men and women). However, in mediation analysis, it was found that the majority of BMI effect on fracture risk was mediated by femoral neck BMD. The overall mediated effect estimates were -0.048 (95% CI, -0.059 to -0.036; p<0.001) in women and -0.030 (95% CI, -0.042 to -0.018; p<0.001) in men. These analyses suggest that there is no significant direct effect of BMI on fracture, and that the observed association between BMI and fracture risk is mediated by femoral neck BMD in both men and women.

Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. OBJECTIVE: High body mass index (BMI) is associated with increased risk of osteoarthritis (OA) and reduced risk of fragility fracture. However, the relationship between fragility fracture and OA remained unclear. This study sought to investigate the effect of bone mineral density (BMD) in the OA-fracture relationship.METHODS: Data from 2412 women and 1452 men aged >45 years in the Dubbo Osteoporosis Epidemiology Study (DOES) were analyzed. Individuals have been followed for up to 22 years (median: 7.5 years; range: 0.1-22 years). Femoral neck BMD (FNBMD) and lumbar spine BMD (LSBMD) was measured by dual energy X-ray absorptiometry (DXA) (GE LUNAR, Madison, WI). The presence of OA was ascertained at baseline by self-reported diagnosis. The incidence of low-trauma fracture was ascertained from X-ray reports.RESULTS: Overall, 29% of women and 26% of men had reported a diagnosis of OA. Fracture risk was significantly higher in women with OA than those without OA (Hazard ratio (HR) = 1.50; 95% confidence interval (CI), 1.28-1.76). However, the association was mainly observed in women with osteopenic BMD (HR = 1.74; 95% CI, 1.38-2.17) and normal-BMD (HR = 1.50; 95% CI, 1.06-2.13) and not in those with osteoporosis. Further analysis revealed that osteopenic women with OA had significant increase in risk of vertebral (HR = 1.85; 95% CI, 1.24-2.75) and limb fracture (HR = 2.49; 95% CI, 1.77-3.48), but not in hip fracture. In men, no comparable relationship was found before and after adjustment for covariates.CONCLUSION: Women with OA have an increased risk of fragility fracture, and the risk was mainly observed in non-osteoporotic group.

This study sought to determine the association between calcaneal quantitative ultrasound (QUS) and fracture risk in individuals without osteoporosis according to the World Health Organization criteria (i.e., BMD T-score > -2.5). We found that calcaneal QUS is an independent predictor of fracture risk in women with non-osteoporotic bone mineral density (BMD). Introduction: More than 50 % of women and 70 % of men who sustain a fragility fracture have BMD above the osteoporotic threshold (T-score > -2.5). Calcaneal QUS is associated with fracture risk. This study aimed to test the hypothesis that low calcaneal QUS is associated with increased fracture risk in individuals with non-osteoporotic BMD. Methods: We included 312 women and 390 men aged 62-90 years with BMD T-score > -2.5 at femoral neck. QUS was measured in broadband ultrasound attenuation (BUA) at the calcaneus using a CUBA sonometer. BMD was measured at the femoral neck (FNBMD) by dual energy X-ray absorptiometry using GE Lunar DPX-L densitometer. The incidences of any fragility fracture were ascertained by X-ray reports during the follow-up period from 1994 to 2011. Results: Of the 702 participants, 26 % of women (n = 80/312) and 14 % of men (n = 53/390) experienced at least one fragility fracture during the follow-up period. In women, after adjusting for covariates, increased risk of any fracture was significantly associated with decreased BUA (HR = 1.50; 95 % CI, 1.13-1.99). Compared with that of FNBMD, the models with BUA, in women, had greater AUC (0.71, 0.85, 0.71 for any, hip and vertebral fracture, respectively), and yielded a net reclassification improvement of 16.4 % (P = 0.009) when combined with FNBMD. In men, BUA was not significantly associated with fracture risk before and after adjustment. Conclusion: These results suggest that calcaneal BUA is an independent predictor of fracture risk in women with non-osteoporotic BMD. © 2012 International Osteoporosis Foundation and National Osteoporosis F

Quantitative ultrasound measurement (QUS) and bone mineral density (BMD) have each been shown to predict fracture risk in women. The present study examined whether a combination of QUS and BMD could improve the predictive accuracy of fracture risk. This is a population-based prospective study which involved 454 women and 445 men aged 62-89 years. Femoral neck BMD (FNBMD) was measured by DXA and calcaneal QUS was measured as broadband ultrasound attenuation (BUA) by a CUBA sonometer. Fragility fracture was ascertained by X-ray reports during the follow-up period, which took place between mid-1989 and 2009. During the follow-up period (median 13 years, range 11-15), 75 men and 154 women sustained a fragility fracture. In women, the model with FNBMD and BUA had a higher AUC compared to that without BUA (0.73 vs. 0.71 for any fracture, 0.81 vs. 0.77 for hip fracture, and 0.72 vs. 0.70 for vertebral fracture). Reclassification analysis yielded a total net reclassification improvement of 7.3%, 11.1%, and 5.2% for any, hip, and vertebral fractures, respectively. For men, the addition of BUA to FNBMD did not improve the predictive power for any, hip, or vertebral fracture. These results suggest that calcaneal QUS is an independent predictor of fracture risk and that a combination of QUS and BMD measurement could improve the predictive accuracy of fracture risk in elderly women. © 2011 Springer Science+Business Media, LLC.

Quantitative ultrasound measurement (QUS) and bone mineral density (BMD) have each been shown to predict fracture risk in women. The present study examined whether a combination of QUS and BMD could improve the predictive accuracy of fracture risk. This is a population-based prospective study which involved 454 women and 445 men aged 62-89 years. Femoral neck BMD (FNBMD) was measured by DXA and calcaneal QUS was measured as broadband ultrasound attenuation (BUA) by a CUBA sonometer. Fragility fracture was ascertained by X-ray reports during the follow-up period, which took place between mid-1989 and 2009. During the follow-up period (median 13 years, range 11-15), 75 men and 154 women sustained a fragility fracture. In women, the model with FNBMD and BUA had a higher AUC compared to that without BUA (0.73 vs. 0.71 for any fracture, 0.81 vs. 0.77 for hip fracture, and 0.72 vs. 0.70 for vertebral fracture). Reclassification analysis yielded a total net reclassification improvement of 7.3%, 11.1%, and 5.2% for any, hip, and vertebral fractures, respectively. For men, the addition of BUA to FNBMD did not improve the predictive power for any, hip, or vertebral fracture. These results suggest that calcaneal QUS is an independent predictor of fracture risk and that a combination of QUS and BMD measurement could improve the predictive accuracy of fracture risk in elderly women. © 2011 Springer Science+Business Media, LLC.

A novel technique is proposed to reduce the computational complexity of discrete cosine transform (DCT)-based video encoders. The proposed method merges the DCT and quantization into a single procedure, which is referred to as the novel quantized DCT (NQDCT), such that the DCT output does not need to be explicitly quantized. Thus, a lot of computations related to quantization can be saved. The video encoder's performance using NQDCT is evaluated by comparing it with those using the traditional separate DCT and quantization method and the quantized DCT (QDCT) method. Simulation results demonstrate that the proposed NQDCT outperforms the other two methods in improving the real-time performance for video encoding.

This paper gives optimal algorithms for the construction of the Nearest Neighbor Embracing Graph (NNE-graph) of a given point set V of size n in the k-dimensional space (k-D) for k = 2,3. The NNE-graph provides another way of connecting points in a communication network, which has lower expected degree at each point and shorter total length of connections with respect to those using Delaunay triangulation. In fact, the NNE-graph can also be used as a tool to test whether a point set is randomly generated or has some particular properties. We show that in 2-D the NNE-graph can be constructed in optimal Theta(n(2)) time in the worst case. We also present an O(n log n + nd) time algorithm, where d is the Omega(log n)-th largest degree in the utput NNE-graph. The algorithm is optimal when d=O(log n). The algorithm is also sensitive to the structure of the NNE-graph, for instance when d=g.(log n), the number of edges in NNE-graph is bounded by O(gn log n) for any value g with 1 <= g <= n/log n. We finally propose an O(n log n + nd log d{*}) time algorithm for the problem in 3-D, where d and d{*} are the Omega(log n/log log n)-th largest vertex degree and the largest vertex degree in the NNE-graph, respectively. The algorithm is optimal when the largest vertex degree of the NNE-graph d{*} is O(log n/log log n).

A novel technique is proposed to reduce the computational complexity of discrete cosine transform (DCT)-based video encoders. The proposed method merges the DCT and quantization into a single procedure, which is referred to as the novel quantized DCT (NQDCT), such that the DCT output does not need to be explicitly quantized. Thus, a lot of computations related to quantization can be saved. The video encoder's performance using NQDCT is evaluated by comparing it with those using the traditional separate DCT and quantization method and the quantized DCT (QDCT) method. Simulation results demonstrate that the proposed NQDCT outperforms the other two methods in improving the real-time performance for video encoding.

This paper gives optimal algorithms for the construction of the Nearest Neighbor Embracing Graph (NNE-graph) of a given point set V of size n in the k-dimensional space (k-D) for k = 2,3. The NNE-graph provides another way of connecting points in a communication network, which has lower expected degree at each point and shorter total length of connections with respect to those using Delaunay triangulation. In fact, the NNE-graph can also be used as a tool to test whether a point set is randomly generated or has some particular properties. We show that in 2-D the NNE-graph can be constructed in optimal Theta(n(2)) time in the worst case. We also present an O(n log n + nd) time algorithm, where d is the Omega(log n)-th largest degree in the utput NNE-graph. The algorithm is optimal when d=O(log n). The algorithm is also sensitive to the structure of the NNE-graph, for instance when d=g.(log n), the number of edges in NNE-graph is bounded by O(gn log n) for any value g with 1 <= g <= n/log n. We finally propose an O(n log n + nd log d{*}) time algorithm for the problem in 3-D, where d and d{*} are the Omega(log n/log log n)-th largest vertex degree and the largest vertex degree in the NNE-graph, respectively. The algorithm is optimal when the largest vertex degree of the NNE-graph d{*} is O(log n/log log n).

A novel technique is proposed to reduce the computational complexity of discrete cosine transform (DCT)-based video encoders. The proposed method merges the DCT and quantization into a single procedure, which is referred to as the novel quantized DCT (NQDCT), such that the DCT output does not need to be explicitly quantized. Thus, a lot of computations related to quantization can be saved. The video encoder's performance using NQDCT is evaluated by comparing it with those using the traditional separate DCT and quantization method and the quantized DCT (QDCT) method. Simulation results demonstrate that the proposed NQDCT outperforms the other two methods in improving the real-time performance for video encoding.

This paper gives optimal algorithms for the construction of the Nearest Neighbor Embracing Graph (NNE-graph) of a given point set V of size n in the k-dimensional space (k-D) for k = 2,3. The NNE-graph provides another way of connecting points in a communication network, which has lower expected degree at each point and shorter total length of connections with respect to those using Delaunay triangulation. In fact, the NNE-graph can also be used as a tool to test whether a point set is randomly generated or has some particular properties. We show that in 2-D the NNE-graph can be constructed in optimal Theta(n(2)) time in the worst case. We also present an O(n log n + nd) time algorithm, where d is the Omega(log n)-th largest degree in the utput NNE-graph. The algorithm is optimal when d=O(log n). The algorithm is also sensitive to the structure of the NNE-graph, for instance when d=g.(log n), the number of edges in NNE-graph is bounded by O(gn log n) for any value g with 1 <= g <= n/log n. We finally propose an O(n log n + nd log d{*}) time algorithm for the problem in 3-D, where d and d{*} are the Omega(log n/log log n)-th largest vertex degree and the largest vertex degree in the NNE-graph, respectively. The algorithm is optimal when the largest vertex degree of the NNE-graph d{*} is O(log n/log log n).

A self-planarizing Au metallization process by selective electrolytic plating was developed for metal interconnections in the submicron range. This process is superior to the conventional gold metallization process and economically viable due to its simplicity and no use of ion-milling. The reaction mechanism of the selective plating between metal and semiconductor electrodes was studied. Voltammetry showed that a much higher deposition potential is required for an oxidized TiW electrode than that for an Au electrode. In this paper, we use the existing TiW barrier layer as part of the electrode during Au plating. Through an O-2 plasma treatment, which is an exiting step for photoresist ashing, we turn the TiW electrode from metallic into semiconducting. Under optimized electrolytic plating conditions, we can selectively plate Au wires into dielectric trenches while leaving the oxidized TiW field free of Au.

A self-planarizing Au metallization process by selective electrolytic plating was developed for metal interconnections in the submicron range. This process is superior to the conventional gold metallization process and economically viable due to its simplicity and no use of ion-milling. The reaction mechanism of the selective plating between metal and semiconductor electrodes was studied. Voltammetry showed that a much higher deposition potential is required for an oxidized TiW electrode than that for an Au electrode. In this paper, we use the existing TiW barrier layer as part of the electrode during Au plating. Through an O-2 plasma treatment, which is an exiting step for photoresist ashing, we turn the TiW electrode from metallic into semiconducting. Under optimized electrolytic plating conditions, we can selectively plate Au wires into dielectric trenches while leaving the oxidized TiW field free of Au.

A self-planarizing Au metallization process by selective electrolytic plating was developed for metal interconnections in the submicron range. This process is superior to the conventional gold metallization process and economically viable due to its simplicity and no use of ion-milling. The reaction mechanism of the selective plating between metal and semiconductor electrodes was studied. Voltammetry showed that a much higher deposition potential is required for an oxidized TiW electrode than that for an Au electrode. In this paper, we use the existing TiW barrier layer as part of the electrode during Au plating. Through an O-2 plasma treatment, which is an exiting step for photoresist ashing, we turn the TiW electrode from metallic into semiconducting. Under optimized electrolytic plating conditions, we can selectively plate Au wires into dielectric trenches while leaving the oxidized TiW field free of Au.