65 research outputs found

    Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

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    Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

    Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci

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    Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies

    Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

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    BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

    The Variation of Carbon Dioxide Concentrations Between Different Stands in GuanDauShi Forest

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    本試驗之目的在探討森林生態系中二氧化碳濃度的空間變化。以及不同林分組成對於林內二氧化碳濃度的影響。樣區設於惠蓀林場關刀溪長期生態研究區,選擇其中之天然闊葉林及人工杉木林進行採樣,兩個林分內各設有三個樣點,每個樣點以冠層為中心設置三個採樣高度進行採樣,同時在兩林分外的開闊地各設一對照樣點。採樣期間為2003年6月,共取得7個採樣週期之二氧化碳濃度資料。採樣時利用儀器持續監測,採樣週期為24小時。 試驗期間,兩林分夜間的二氧化碳濃度均較日間為高,天然闊葉林夜間的二氧化碳濃度(412.4±12.5 ppm)略高於人工杉木林(399.2±15.3 ppm),日間則是人工杉木林(395.6±15.3 ppm) 略高於天然闊葉林 (391.0±9.0 ppm)。兩林分的二氧化碳濃度在垂直高度上有不同的變化趨勢,天然闊葉林以冠層下方之二氧化碳濃度最高(406.9±14.3 ppm),人工杉木林則以冠層處的二氧化碳濃度最高(407.4±13.1 ppm)。 影響二氧化碳濃度最重要的因子為光度及二氧化碳本身之日變化,二氧化碳濃度與光度常呈負相關,亦即二氧化碳濃度會隨光度上升而下降。試驗期間,光度最大值通常出現在早上10點到正午間,二氧化碳濃度最小值出現的時間則稍晚,約在正午到下午3點間。CO2 concentrations within a China-fir plantation and a natural hardwood stand were measured to explore the distribution of CO2 and the effect of stand composition in forest ecosystem. The experiment site locates in Guandaushi Long Term Ecological Research site in Nantou. We chose three sampling plots in each stand, three sampling heights were set in each plot. Contrast plots were set at three sampling heights outside each stand. LI-COR 6252 was used to offer 24-hour continuous sampling, each sampling period sustained 24 hours at least. During the experiment period, nighttime CO2 concentrations were higher than daytime CO2 concentrations in each stand. Nighttime CO2 concentrations in natural stand(412.412.5 ppm) were higher than China-fir plantation(399.215.3 ppm). But daytime CO2 concentrations in China-fir plantation (395.615.3 ppm) were higher than natural stand(391.09.0 ppm). CO2 concentration showed different trends in different stands. The highest CO2 concentrations appeared below canopy in nature hardwood stand(406.914.3 ppm), but appeared within canopy in China-fir plantation(407.413.1 ppm). The most important factors that influence CO2 concentrations were diurnal CO2 concentration variance and light intensity. CO2 concentrations usually increase while light intensity decreases. During experiment period, the maximum light intensity values appeared between AM 10:00 and noon, but the minimum CO2 concentration values appeared between noon and PM 15:00.中文摘要 Ⅰ 英文摘要 Ⅱ 目錄 Ⅲ 表目次 Ⅴ 圖目次 Ⅵ 照片目次 Ⅶ 壹、前言 1 貳、前人研究 3 一、環境因子對植物生長的影響 3 二、影響二氧化碳濃度的因子 3 三、二氧化碳的空間分布及流動 5 參、材料與方法 7 一、樣區位置 7 二、環境因子 7 (一)溫溼度紀錄 7 (二)輻射量採樣 7 三、氣體採樣 8 (一)林外樣點設置 8 (二)林內樣點設置 8 (三)氣體流通 9 (四)採樣氣體偵測 9 (五)採樣間隔與採樣數據之關聯 10 (六)二氧化碳分析儀校正 10 肆、結果 17 一、環境因子之變化 17 (一)日照 17 (二)溫溼度 18 二、採樣間隔與採樣數據之關聯 19 三、二氧化碳分析儀校正 20 四、二氧化碳濃度之空間變化 21 (一)全天二氧化碳濃度比較 21 (二)日夜二氧化碳濃度比較 22 五、二氧化碳濃度之時間變化 24 (一)天然闊葉林二氧化碳濃度在不同時間之變化 24 (二)人工杉木林二氧化碳濃度在不同時間之變化 24 六、二氧化碳濃度在不同光度時之變化 26 (一)天然闊葉林二氧化碳濃度在不同光度時之變化 26 (二)人工杉木林二氧化碳濃度在不同光度時之變化 27 伍、討論 28 陸、結論 31 柒、引用文獻 32 捌、附錄 3

    The Hospice Information System and its association with the congruence between the preferred and actual place of death

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    Objective: A Hospice Information System (HIS) developed in eastern Taiwan in 2012 aimed to improve the quality of hospice care through an integrated system that provided telemetry-based vital sign records, online 24/7 consultations, online video interviews, and online health educations. The purpose of this study was to explore the congruence between the preferred and actual place of death (POD) among patients who received HIS services. Materials and Methods: A retrospective study was performed from January 2012 to August 2016. Data from patients enrolled in the HIS who died during this period were included. Data on basic characteristics and the actual and preferred POD were obtained from the HIS database. The primary outcome was the congruence between the preferred and actual POD. Secondary outcomes were comparisons between patients who did and did not achieve their preferred POD. Further comparisons between patients who did and did not achieve home death were also performed. Results: In total, we enrolled 481 patients who received HIS services and died. Of them, 444 (92.3%) died at their preferred POD. Patients who preferred an inpatient hospice as their POD had higher achievement rate than those who wanted a home death. High-intensity HIS utilization was associated with a higher likelihood of home death than low-intensity HIS utilization. Patients living in areas distant from the medical center had lower achievement of home death than those living in local areas. Conclusions: This study suggested that patients enrolled in the HIS had high congruence between the actual and preferred POD

    High Incidence of Mammalian Orthoreovirus Identified by Environmental Surveillance in Taiwan.

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    Wild poliovirus (WPV) persists in diverse locales worldwide, spreading outward from endemic areas. In response to the international threat of WPV transmission and changes in the national vaccination policy, we established an environmental surveillance system to monitor the circulation of wild and vaccine-related poliovirus in Taiwan. From July 2012 to December 2013, we collected sewage specimens every month from 10 sewage treatment plants located throughout Taiwan. The specimens were concentrated by the two-phase separation method and then inoculated into L20B, RD, and A549 cells for virus isolation. Viral isolates were identified and serotyped by immunofluorescence assay or molecular analysis. A total of 300 sewage samples were collected, and the results showed 163 samples (54.3%) were positive for virus, and 268 isolates were identified. Among these, 75 samples (25%) were positive for enterovirus (EV), but no poliovirus was found. In addition, 92 isolates were identified as enteroviruses and the most common serotypes were coxsackievirus B4, coxsackievirus B3, and coxsackievirus B2. Interestingly, 102 (34%) and 82 (27.3%) specimens were positive for mammalian orthoreovirus (MRV) and adenovirus, respectively. This study confirmed that sewage surveillance can be a useful additional modality for monitoring the possible presence of wild-type or vaccine-derived poliovirus in wastewater, and can indicate the current types of viruses circulating in the population. Furthermore, since MRV was found in children with acute necrotizing encephalopathy and meningitis, the high incidence of MRV detected by environmental surveillance warrants further investigation
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