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The influence of Li doping on the crystallization, surface morphology and luminescent properties of CaTiO3 : Pr3+ films has been investigated. The films were grown on Al2O3 (0 0 0 1) substrates using the pulsed laser deposition method under different oxygen pressures. The substrate temperature was fixed at 700 °C and the range of oxygen pressure was 100–400 mTorr. The crystallinity and surface morphology of the films were investigated using x-ray diffraction and atomic force microscopy, respectively. The emitted radiation at 322 nm excitation was dominated by a red emission peak at 613 nm radiated from the transition of 1D2 → 3H4 of Pr3+ ions. In particular, the incorporation of Li+ ions into the CaTiO3 lattice could induce the increase in the intensity of the photoluminescence. The enhanced luminescence may result not only from the improved crystallinity but also from the reduced internal reflections caused by rougher surfaces. The luminescent intensity and surface roughness exhibited similar behaviour as a function of the oxygen pressure.

Background: Noninvasive measurement of carotid artery intima media thickness (IMT) has been widely used as a surrogate marker of coronary atherosclerosis. However, evidence for the clinical implications of increased carotid IMT in diabetic patients is not well established. The aim of this study was to determine if coronary artery disease (CAD) can be predicted based on carotid IMT, intimal, and medial thickness. Methods: A total of 569 type 2 diabetic patients (male:female=311:258, mean age=63±9 years) who underwent coronary angiography were divided into two groups. Group 1 was composed of patients with no significant CAD (n=105, male%=37.1%, mean age=61±10 years) on angiography. Group 2 was composed of patients with significant CAD (n=464. male%=58.6%, mean age=64±9 years). Carotid intimal, medial thickness, and IMT were compared between the two groups. Sensitivity and specificity for detecting significant CAD by carotid ultrasound were evaluated. Results: There were significant differences in the right maximal IMT, mean IMT, and medial thickness for both carotid arteries. However, there were no significant differences in the left maximal IMT and intimal thickness (Table). A right IMT of 1.13mm and a left IMT of 1.19mm had 94% sensitivity and 80% specificity for CAD, respectively. A right medial thickness of 0.99mm and a left medial thickness of 1.03mm had 100% sensitivity and 86% specificity. Conclusion: Carotid medial thickness and IMT were useful as screening methods for detecting significant CAD in patients with diabetes.

Background : In vitro experimental studies have reported that transforming growth factor-β 1 (TGF-β 1) stimulates the production of α -smooth muscle actin (α -SMA) in porcine valves. However, the relation between TGF-β 1 and α -SMA in myxomatous valves has not been elucidated. Methods : We classified 27 subjects into two groups: 1) myxomatous group (M:F=11:12, mean age=55±15 years) and 2) rheumatic group (M:F=3:1, mean age=41±17 years) according to preoperative echocardiographic and postoperative histologic findings. Twenty-seven valve specimens from the patients who underwent valve replacement were obtained. Tissue samples were analyzed by immunohistochemistry for TGF-β 1 and α -SMA. The positively stained areas were measured using an image analysis program (Image Pro-Plus 4.5), and then the TGF-β 1 volume fraction (TGF-VF) and α -SMA volume fraction (α -SMA-VF) were calculated. Results : TGF-VF in myxomatous valves was higher than in rheumatic valves (2,759±2,294 vs 864±276, p=0.04). α -SMA-VF in myxomatous valves was higher than in rheumatic valves (4,122±2,275 vs 2,421±844, p=0.002). There was a significant correlation between TGF-β 1 and α -SMA in myxomatous valves (r=0.38, p=0.04). There was no significant correlation between TGF-β 1 and α -SMA in rheumatic valves (r=-0.50, p=0.67). Conclusions : TGF-β 1 and α -SMA may be related to the pathogenesis of myxomatous valves. The activation of TGF-β 1 might increase the expression of α -SMA in human myxomatous valves.

Background: Calcium scoring on MDCT and carotid intima-media thickness (IMT) have been widely used as indices of atherosclerosis. However, the clinical correlation between carotid IMT and the severity of coronary artery disease (CAD) is relatively poorly established. The aim of this study was to determine the relation between coronary restenosis after DES implantation and carotid IMT. Methods: Among a total of 3041 patients who underwent carotid ultrasonography, 956 patients (male:female=583:373, mean age=61±11 years) with DES implantation who had undergone follow-up coronary angiography were divided into two groups. Group 1 (n=861, male=61%, mean age 60±11 years) was the no ISR group. Group 2 (n=95, male=67.4%, mean age=65±9 years) was the ISR group. ISR was defined as a more than 50% reduction in luminal stent diameter on follow-up coronary angiography. Carotid IMT was measured using a 15MHz high frequency transducer on the far walls of both carotid arteries. Intimal thickness, defined as high echogenic thickening in the intimal area on carotid ultrasound, was also measured. The calcium score on MDCT was also compared between the two groups. Results: On comparison between the two groups (group 1 vs group 2), 1. The right mean IMT and media thickness were larger in Group 1 (p=0.023, p=0.048). 2. There was no significant difference in the right and left maximal IMT or left medial thickness (Table). 3. Calcium scores were significantly higher on MDCT in the ISR group (427±86 vs 1599±482, p

Background: The cold pressor test (CPT) has been used to detect vasospastic angina, but its sensitivity for predicting vasospasm is low. The aim of this study was to determine if the estimation of coronary flow reserve capacity in the left anterior descending coronary artery using transthoracic Doppler echocardiography (TTE) and CPT can predict coronary artery spasm. Methods: A provocation test of coronary artery spasm using acetylcholine (50 and 80 μg) was performed in 65 subjects (52±10 yrs, M:F=41:24) with chest pain and normal coronary angiograms. Before and during CPT, the peak (PDV) and mean diastolic flow velocity (MDV) of the distal left anterior descending coronary artery were estimated using high frequency TTE (Figure), and ECG, blood pressure, and symptoms were monitored every minute. CPT%PDV and CPT%MDV were defined as the % change of PDV and MDV during CPT, respectively. The subjects were divided into two groups??(Spasm+group, 31) and (Spasm-group, 34)]?? and compared. Results: 1. The CPT%PDV was 52.75±24% in the Spasm-group and 4.99±23.62% in the Spasm + group (p

We have designed and synthesized self-assembled one-dimensional nanowires (1D NWs) from the fused thiophene derivative 2,3-bis(5-(3,5-bis(trifluoromethyl)phenyl)thiophen-2-yl)acrylonitrile (SS-TFMBE). This new material is characterized by a strong self-assembling capability that leads to the formation of 1D NWs exhibiting a dramatic increase in fluorescence emission upon formation of NW aggregates. In addition, the semiconducting properties of the 1D NWs were evidenced by means of conducting-probe atomic force microscopy (CP-AFM) and space-charge-limited-current (SCLC) measurements, which show that SS-TFMBE NWs composed of ordered percolated crystals have an effective carrier mobility of up to 3.1 cm2V−1 s−1.

Isolated left ventricular noncompaction cardiomyopathy (IVNC) is a cardiomyopathy thought to be caused by arrest of normal embryogenesis of the endocardium and myocardium. This abnormality is often associated with other congenital cardiac defects. A 21-year-old man presented to the emergency department with worsening exertional dyspnea during the previous 2 months. Two-dimensional and Doppler echocardiography revealed an enlarged left atrium (LA) and a markedly dilated left ventricle (LV) with preserved LV systolic function, severe mitral valve regurgitation, and prolapse due to chordae rupture. The myocardium of the LV and right ventricle (RV) had excessively prominent trabeculations and deep intertrabecular recesses. He is the first patient in Korea who has undergone mitral valve replacement surgery because of severe mitral valve regurgitation and prolapse due to chordae rupture accompanied by IVNC.

Background and Objectives: Intensive lipid-lowering therapy with statins improves the clinical outcomes and patient survival and it reduces the progression of atherosclerosis. Intravascular ultrasound (IVUS) has been used for calculating the plaque volumes to evaluate the mechanisms that may be involved in the progression or regression of coronary artery disease. We used serial IVUS exams to assess the efficacy of rosuvastatin on plaque regression in angina patients who had a mild to moderate degree of vulnerable plaque burden. Subjects and Methods: This study was a prospective, randomized, comparative study for lipid lowering therapy with using rosuvastatin 20 mg or atorvastatin 40 mg. IVUS was performed during the baseline coronary angiography and it was repeated after 12 months of treatment. The efficacy parameters included the changes in the atheroma volume and the lipid pool size as determined by IVUS. A total of 45 lesions in 30 patients were analyzed (rosuvastatin: 24 lesions in 16 patients vs. atorvastatin: 21 lesions in 14 patients). Results: The low density lipoprotein (LDL)-cholesterol level was reduced from 121±45 mg/dL to 65±25 mg/dL in the rosuvastatin group (a 46% decrease, p

We demonstrate a simple vapor-phase fabrication of self-assembled perpendicular organic nanoneedles on various substrates to generate superhydrophobic surfaces on them.

Background and Objectives: Findings from randomized controlled trials have showed that there is no difference in the development of stent thrombosis (ST) in patients implanted with drug-eluting stents (DES) as compared to the use of bare metal stents. The aim of this study was to evaluate the incidence, clinical characteristics, and clinical outcome of ST after implantation of TAXUS stents in routine clinical practice. Subjects and Methods: This was a retrospective, single center cohort study. The study included 1,584 patients that underwent successful TAXUS stent implantation (2,513 lesions treated) between May 2004 and Dec 2006. Results: ST developed in 18 patients (1.14%) of the 1,584 patients. Acute ST occurred in one patient (0.06%), subacute ST occurred in nine patients (0.57%), and late ST developed in eight patients (0.51%). Sixteen patients that developed ST received medication with dual antiplatelet agents. The incidence of ST in patients with acute coronary syndrome (ACS) showed was higher than in patients with stable coronary disease. The mean follow-up duration for patients was 13.3 months. There were 13 myocardial infarctions and 3 deaths attributable to ST. Conclusion: The cumulative incidence of ST that was confirmed by angiography after successful TAXUS stent implantation in consecutive “real-world” patients was substantially higher than the rate reported in clinical trials. Patients with ACS should be treated more aggressively as the risk of stent thrombosis is higher than for patients with stable angina. A large prospective study for the identification of predictors of DES thrombosis should be conducted. (Korean Circ J 2007;37:641-646)

Background and Objectives:Systemic activation of the inflammatory system after aortic injury may play a role in the development of complications. The aim of this study was to determine the significance of the inflammatory markers for the mortality of patients suffering with medically treated type B acute aortic syndrome (AAS). Subjects and Methods:We analyzed a total of 81 patients who were admitted with AAS within 24 hours from the onset of the symptoms and who were medically treated between January 2000 and December 2004. The patients were divided into two groups: the moribund patients who died within 2 weeks (group I: n=8, mean age: 64.0± 11.0 years) and the patients who survived over 2 weeks (group II: n=73, mean age: 62.6±13.7 years). The serum high-sensitivity C-reactive protein (hsCRP) levels, the white blood cell (WBC) and monocyte counts, and the plasma D-dimer levels were measured on admission. Results:The baseline clinical characteristics were not different between the two groups. The major causes of in-hospital death in group I were extensions or rupture of type B dissection (6 cases) and acute renal failure (2 cases). The multivariate analysis demonstrated that a high monocyte count (>1,250/mm), and high levels of hsCRP (>11 mg/dL) and D-dimer (>1.2 mg/dL) were independent determinants of the short-term mortality (OR=6.39, 6.14 and 9.00; 95% CI=1.19 to 34.1, 1.14 to 32.9 and 1.20 to 67.4; p=0.02, 0.04 and 0.03, respectively). Conclusion:Systemic activation of the inflammatory system in type B AAS patients may be one of the important factors associated with the development of shortterm mortality. (Korean Circulation J 2006;36:387-392)

Purpose : To evaluate the effectiveness of a polylactic acid bioresorbable film in the prevention of tendon adhesion after tendon repair. Materials and Methods : Twenty-four adult rabbits (48 cases) were used in this study. In the first (control) group, the flexor tendons of the third toe were cut and a tenorrhaphy was performed. The 2nd group was injected with hyaluronic acid between the tendon and tendon sheath after suturing. The 3rd group underwent an enveloping of the tendon with polylactic acid film, followed by tenorrhaphy. The test animals were euthanized at 1, 2, 3, and 6 weeks after surgery, and the histology and biomechanics were evaluated. Results : Microscopic evaluations revealed fibrosis to be most apparent in group 1, while groups 2 and 3 showed no significant differences. The biomechanical tests, which were carried out using a Universal Testing Machine, revealed that an increase in adhesion strength with time. At 6 weeks after surgery, group 1 exhibited an adhesion strength that was 2.5-3 times greater than that exhibited by groups 2 and 3. Group 2 had a higher adhesion strength than group 3, but this difference was not statistically significant. Conclusion : Increases in granulation tissue and fibrosis during the healing of sutured tendons were observed, and the tested polylactide resorbable film was found to be effective in reducing the level of adhesion formation after tendon repair.

Purpose : This study evaluated the minimum ten-year result of primary total hip arthroplasty with a non-cemented Multilock femoral stem. Materials and Methods : Fifty five total hip replacements in forty-four patients using a noncemented Multilock femoral stem and Harris-Galante 2 acetabular component were performed between January 1992 and December 1994. Forty-four hips in thirty-six patients were available for follow up for an average of eleven years (range, ten to twelve years). The clinical results were evaluated based on the Harris hip scores. A detailed radiography analysis was performed by an evaluation of the radiolucent lines, femoral osteolysis, and fixation stability by Engh Method. Results : The average Harris hip score improved from 54.3 points preoperatively to 93.6 points postoperatively. Non-progressive radiolucencies ＜2 mm in width were observed in nine (20.5%), and femoral osteolysis was observed in thirteen cases (29.5%). For the fixation stability, osseous ingrowth was noted in thirty nine cases (88.6%) and fibrous ingrowth was observed in two (4.5%). There were three (6.8%) cases with unstable fixation. Two hips underwent revision. The survival rate of the femoral component was 93.2% (forty one cases) after a minimum ten-year follow up. Conclusion : The non-cemented Multilock femoral component provided excellent clinical and radiographic results. However, the rate of femoral osteolysis was relatively high (mostly restricted to zone 1 and 7).

Purpose : A retrograde analysis of the clinical results of 11 cases of Kienbock's disease (Lichtman stage III), who underwent surgery for scaphocapitate or hamatocapitate arthrodesis followed by a rolled palmaris tendon replacement after a collapsed lunate excision. Materials and Methods : This study followed-up 11 patients diagnosed with advanced Kienbock's disease for more than 5 years from January 1989 through May 2000. The patient’s age ranged from 25 to 65 years old. Among the 11 patients, 7 patients received hamatocapitate arthrodesis, and the remainder received scaphocapitate arthrodesis. The Evans’ scoring system was used for the clinical evaluation. Results : After surgery, all patients showed complete radiologic fusion and an increase in grip strength, and most patients showed an increase in the ROM of a wrist joint, particularly in the group who received hamatocapitate arthrodesis. Conclusion : In advanced Kienbock’s disease, a lunate excision followed by rolled tendon replacement with limited intercarpal arthrodesis showed relatively good results during the follow-up period, and had a particularly better ROM of the wrist joint in hamatocapitate arthrodesis, than the scaphocapitate arthrodesis because of the arthrodesis between the proximal and distal carpal row in the biomechanical aspect of the carpal bone.

목 적: 불안정성 대퇴골 전자간부 골절에서 활강 압박 고나사와 함께 전자부 안정화 금속판 (TSP)을 사용한 수술적 치료의 결과를 분석하고저 하였다. 대상 및 방법: 2002년 1월부터 2004년 12월까지 본원 정형외과에서 대퇴골 전자간 골절 진단하에 활강 압박 고나사와 함께 전자부 안정화 금 속판 (TSP)을 이용해서 수술적 치료를 받은 23례 중 60세 이상이며 1년 이상 추시가 가능하였고 AO분류상 A2, A3형의 불안정성 골절로 분 류된 17명의 환자를 대상으로 하였다. AO분류에 의한 골절 유형, 연령, 성별, 수상 원인 등을 분석하였고 수술 직후와 최종 추시 시의 전후면 방사선 사진 상 지연 나사의 활강 정도, 경간각의 변화, 대자부의 외측 전위 및 골유합 기간을 측정하였고 수술 후 지연 나사의 첨단부의 3 mm 이상의 전위 또는 골두 천공을 고정 실패로 정의하였다. 결 과: 골유합 기간은 평균 12주였고, 지연 나사의 활강 정도는 평균 8.22 mm, 경간각 변화는 평균 2.66도였으며, 대전자부의 외측 전위는 12례에서는 관찰되지 않았고 5례에서는 평균 0.8 mm의 전이를 나타냈다. 고정 실패가 발생한 예는 없었다. 결 론: 대퇴골 전자간부 불안정 골절에서 활강 압박 고나사와 함께 전자부 안정화 금속판 (TSP)을 이용한 치료는 지연 나사의 활강과 경간각 의 변화를 감소시키고 대전자부의 외측 전위를 일으키지 않으므로 고정 실패를 감소시킬 수 있을 것으로 사료된다.

목 적: 불안정성 대퇴골 전자간부 골절에서 수술적 치료 후 고정 실패에 영향을 미치는 인자들의 중요도를 규명하고자 하였다. 대상 및 방법: 1997년 1월부터 2002년 12월까지 대퇴골 전자간부 골절로 압박고 나사를 이용해서 수술한 환자 중 1년 이상 이상 추시가 가능하였고 AO분류상 A2, A3형의 불안정성 골절로 분류된 82명의 환자를 대상으로 하였다. 수술 후 지연나사의 첨단부의 3 mm 이상의 전위 또는 골두 천공을 고정 실패로 정의 하였으며 연령, 골조송증의 정도, 골절형태, 대퇴 경간각, 골절편 전위 정도, 감입 정도, 정복 형태, 지연나사의 위치 등의 방사선학 적 계측 결과를 분석하여 고정실패에 영향을 미치는 인자를 후향적으로 분석하였다. 결 과: 82명의 환자 중 9명 (10.9%)에서 고정실패가 발생하였다. 골절분류 A2.3와 A3에서 고정 실패율이 증가하였으며 수술 직후 원위 골절 편의 전위가 고정 실패가 발생하지 않은 예에서보다 증가된 결과를 보였으며 통계적으로 유의하였다. 그러나, 연령, 골조송증의 정도, 대퇴 경 간각, 감입 정도, 정복 형태, 지연나사의 위치와 고정실패와의 유의성은 보이지 않았다. 결 론: 대퇴골 전자간부 불안정 골절에서는 활강 압박고나사만을 이용한 고정은 실패가 발생할 가능성이 높으므로 다른 방법의 고정 또는 보 강하는 방법을 고려해야 할 것으로 사료된다.

Publisher's version (útgefin grein), Objective: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n=20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. Results: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p[BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p[BI]= 4.4 × 10-10; p [SSBI] = 1.2 × 10 -4), diabetes (p[BI] = 1.7 × 10 -8; p [SSBI] = 2.8 × 10 -3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10 -24), and MRI-defined white matter hyperintensity burden (p [BI]=1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. Conclusion: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI., CHAP: R01-AG-11101, R01-AG-030146, NIRP-14-302587. SMART: This study was supported by a grant from the Netherlands Organization for Scientific Research–Medical Sciences (project no. 904-65–095). LBC: The authors thank the LBC1936 participants and the members of the LBC1936 research team who collected and collated the phenotypic and genotypic data. The LBC1936 is supported by Age UK (Disconnected Mind Programme grant). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1). The brain imaging was performed in the Brain Research Imaging Centre (https://www.ed.ac.uk/clinical-sciences/edinburgh-imaging), a center in the SINAPSE Collaboration (sinapse.ac.uk) supported by the Scottish Funding Council and Chief Scientist Office. Funding from the UK Biotechnology and Biological Sciences Research Council (BBSRC) and the UK Medical Research Council is acknowledged. Genotyping was supported by a grant from the BBSRC (ref. BB/F019394/1). PROSPER: The PROSPER study was supported by an investigator-initiated grant obtained from Bristol-Myers Squibb. Prof. Dr. J.W. Jukema is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Support for genotyping was provided by the seventh framework program of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810). SCES and SiMES: National Medical Research Council Singapore Centre Grant NMRC/CG/013/2013. C.-Y.C. is supported by the National Medical Research Council, Singapore (CSA/033/2012), Singapore Translational Research Award (STaR) 2013. Dr. Kamran Ikram received additional funding from the Singapore Ministry of Health's National Medical Research Council (NMRC/CSA/038/2013). SHIP: SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, as well as the Social Ministry of the Federal State of Mecklenburg–West Pomerania, and the network “Greifswald Approach to Individualized Medicine (GANI_MED)” funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthineers, Erlangen, Germany, and the Federal State of Mecklenburg–West Pomerania. Whole-body MRI was supported by a joint grant from Siemens Healthineers, Erlangen, Germany, and the Federal State of Mecklenburg–West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH. OATS (Older Australian Twins Study): OATS was supported by an Australian National Health and Medical Research Council (NHRMC)/Australian Research Council (ARC) Strategic Award (ID401162) and by a NHMRC grant (ID1045325). OATS was facilitated via access to the Australian Twin Registry, which is supported by the NHMRC Enabling Grant 310667. The OATS genotyping was partly supported by a Commonwealth Scientific and Industrial Research Organisation Flagship Collaboration Fund Grant. NOMAS: The Northern Manhattan Study is funded by the NIH grant “Stroke Incidence and Risk Factors in a Tri-Ethnic Region” (NINDS R01NS 29993). TASCOG: NHMRC and Heart Foundation. AGES: The study was funded by the National Institute on Aging (NIA) (N01-AG-12100), Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament), with contributions from the Intramural Research Programs at the NIA, the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Neurological Disorders and Stroke (NINDS) (Z01 HL004607-08 CE). ERF: The ERF study as a part of European Special Populations Research Network (EUROSPAN) was supported by European Commission FP6 STRP grant no. 018947 (LSHG-CT-2006-01947) and also received funding from the European Community's Seventh Framework Programme (FP7/2007–2013)/grant agreement HEALTH-F4-2007-201413 by the European Commission under the programme “Quality of Life and Management of the Living Resources” of 5th Framework Programme (no. QLG2-CT-2002-01254). High-throughput analysis of the ERF data was supported by a joint grant from Netherlands Organization for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). Exome sequencing analysis in ERF was supported by the ZonMw grant (project 91111025). Najaf Amin is supported by the Netherlands Brain Foundation (project no. F2013[1]-28). ARIC: The Atherosclerosis Risk in Communities study was performed as a collaborative study supported by NHLBI contracts (HHSN268201100005C, HSN268201100006C, HSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL70825, R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and NIH contract HHSN268200625226C. Infrastructure was partly supported by grant no. UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. This project was also supported by NIH R01 grant NS087541 to M.F. FHS: This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (contracts no. N01-HC-25195 and no. HHSN268201500001I), and its contract with Affymetrix, Inc. for genotyping services (contract no. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. This study was also supported by grants from the NIA (R01s AG033040, AG033193, AG054076, AG049607, AG008122, and U01-AG049505) and the NINDS (R01-NS017950, UH2 NS100605). Dr. DeCarli is supported by the Alzheimer's Disease Center (P30 AG 010129). ASPS: The research reported in this article was funded by the Austrian Science Fund (FWF) grant nos. P20545-P05, P13180, and P20545-B05, by the Austrian National Bank Anniversary Fund, P15435, and the Austrian Ministry of Science under the aegis of the EU Joint Programme–Neurodegenerative Disease Research (JPND) (jpnd.eu). LLS: The Leiden Longevity Study has received funding from the European Union's Seventh Framework Programme (FP7/2007–2011) under grant agreement no. 259679. This study was supported by a grant from the Innovation-Oriented Research Program on Genomics (SenterNovem IGE05007), the Centre for Medical Systems Biology, and the Netherlands Consortium for Healthy Ageing (grant 050-060-810), all in the framework of the Netherlands Genomics Initiative, Netherlands Organization for Scientific Research (NWO), UnileverColworth, and by BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO 184.021.007). CHS: This CHS research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC15103, and HHSN268200960009C and grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, R01HL085251, and R01HL130114 from the NHLBI with additional contribution from NINDS. Additional support was provided through R01AG023629 from the NIA. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Rotterdam Study: The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research (NWO) Investments (no. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/NWO project no. 050-060-810. The Rotterdam Study is funded by Erasmus MC Medical Center and Erasmus MC University, Rotterdam, Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. M.A.I. is supported by an NWO Veni grant (916.13.054). The 3-City Study: The 3-City Study is conducted under a partnership agreement among the Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Bordeaux, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Mutuelle Générale de l’Education Nationale (MGEN), Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Programme “Cohortes et collections de données biologiques.” C.T. and S.D. have received investigator-initiated research funding from the French National Research Agency (ANR) and from the Fondation Leducq. S.D. is supported by a starting grant from the European Research Council (SEGWAY), a grant from the Joint Programme of Neurodegenerative Disease research (BRIDGET), from the European Union's Horizon 2020 research and innovation programme under grant agreements No 643417 & No 640643, and by the Initiative of Excellence of Bordeaux University. Part of the computations were performed at the Bordeaux Bioinformatics Center (CBiB), University of Bordeaux. This work was supported by the National Foundation for Alzheimer's Disease and Related Disorders, the Institut Pasteur de Lille, the Labex DISTALZ, and the Centre National de Génotypage. ADGC: The Alzheimer Disease Genetics Consortium is supported by NIH. NIH-NIA supported this work through the following grants: ADGC, U01 AG032984, RC2 AG036528; NACC, U01 AG016976; NCRAD, U24 AG021886; NIA LOAD, U24 AG026395, U24 AG026390; Banner Sun Health Research Institute, P30 AG019610; Boston University, P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, R01AG33193; Columbia University, P50 AG008702, R37 AG015473; Duke University, P30 AG028377, AG05128; Emory University, AG025688; Group Health Research Institute, UO1 AG06781, UO1 HG004610; Indiana University, P30 AG10133; Johns Hopkins University, P50 AG005146, R01 AG020688; Massachusetts General Hospital, P50 AG005134; Mayo Clinic, P50 AG016574; Mount Sinai School of Medicine, P50 AG005138, P01 AG002219; New York University, P30 AG08051, MO1RR00096, UL1 RR029893, 5R01AG012101, 5R01AG022374, 5R01AG013616, 1RC2AG036502, 1R01AG035137; Northwestern University, P30 AG013854; Oregon Health & Science University, P30 AG008017, R01 AG026916; Rush University, P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146; TGen, R01 NS059873; University of Alabama at Birmingham, P50 AG016582, UL1RR02777; University of Arizona, R01 AG031581; University of California, Davis, P30 AG010129; University of California, Irvine, P50 AG016573, P50, P50 AG016575, P50 AG016576, P50 AG016577; University of California, Los Angeles, P50 AG016570; University of California, San Diego, P50 AG005131; University of California, San Francisco, P50 AG023501, P01 AG019724; University of Kentucky, P30 AG028383, AG05144; University of Michigan, P50 AG008671; University of Pennsylvania, P30 AG010124; University of Pittsburgh, P50 AG005133, AG030653; University of Southern California, P50 AG005142; University of Texas Southwestern, P30 AG012300; University of Miami, R01 AG027944, AG010491, AG027944, AG021547, AG019757; University of Washington, P50 AG005136; Vanderbilt University, R01 AG019085; and Washington University, P50 AG005681, P01 AG03991. The Kathleen Price Bryan Brain Bank at Duke University Medical Center is funded by NINDS grant NS39764, NIMH MH60451, and by GlaxoSmithKline. Genotyping of the TGEN2 cohort was supported by Kronos Science. The TGen series was also funded by NIA grant AG041232, the Banner Alzheimer's Foundation, The Johnnie B. Byrd Sr. Alzheimer's Institute, the Medical Research Council, and the state of Arizona and also includes samples from the following sites: Newcastle Brain Tissue Resource (funding via the Medical Research Council [MRC], local NHS trusts, and Newcastle University), MRC London Brain Bank for Neurodegenerative Diseases (funding via the Medical Research Council), South West Dementia Brain Bank (funding via numerous sources including the Higher Education Funding Council for England [HEFCE], Alzheimer's Research Trust [ART], BRACE, as well as North Bristol NHS Trust Research and Innovation Department and DeNDRoN), The Netherlands Brain Bank (funding via numerous sources including Stichting MS Research, Brain Net Europe, Hersenstichting Nederland Breinbrekend Werk, International Parkinson Fonds, Internationale Stiching Alzheimer Onderzoek), Institut de Neuropatologia, Servei Anatomia Patologica, and Universitat de Barcelona). ADNI: Funding for ADNI is through the Northern California Institute for Research and Education by grants from Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., Alzheimer's Association, Alzheimer's Drug Discovery Foundation, the Dana Foundation, and the National Institute of Biomedical Imaging and Bioengineering and NIA grants U01 AG024904, RC2 AG036535, and K01 AG030514. Support was also provided by the Alzheimer's Association (LAF, IIRG-08-89720; MAP-V, IIRG-05-14147) and the US Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program. SiGN: Stroke Genetic Network (SiGN) was supported in part by award nos. U01NS069208 and R01NS100178 from NINDS. Genetics of Early-Onset Stroke (GEOS) Study was supported by the NIH Genes, Environment and Health Initiative (GEI) grant U01 HG004436, as part of the GENEVA consortium under GEI, with additional support provided by the Mid-Atlantic Nutrition and Obesity Research Center (P30 DK072488); and the Office of Research and Development, Medical Research Service, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs. Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the NIH to Johns Hopkins University (contract no. HHSN268200782096C). Assistance with data cleaning was provided by the GENEVA Coordinating Center (U01 HG 004446; PI Bruce S. Weir). Study recruitment and assembly of datasets were supported by a Cooperative Agreement with the Division of Adult and Community Health, Centers for Disease Control and Prevention, and by grants from NINDS and the NIH Office of Research on Women's Health (R01 NS45012, U01 NS069208-01). METASTROKE: ASGC: Australian population control data were derived from the Hunter Community Study. This research was funded by grants from the Australian National and Medical Health Research Council (NHMRC Project Grant ID: 569257), the Australian National Heart Foundation (NHF Project Grant ID: G 04S 1623), the University of Newcastle, the Gladys M Brawn Fellowship scheme, and the Vincent Fairfax Family Foundation in Australia. E.G.H. was supported by a Fellowship from the NHF and National Stroke Foundation of Australia (ID: 100071). J.M. was supported by an Australian Postgraduate Award. BRAINS: Bio-Repository of DNA in Stroke (BRAINS) is partly funded by a Senior Fellowship from the Department of Health (UK) to P.S., the Henry Smith Charity, and the UK-India Education Research Institutive (UKIERI) from the British Council. GEOS: Genetics of Early Onset Stroke (GEOS) Study, Baltimore, was supported by GEI Grant U01 HG004436, as part of the GENEVA consortium under GEI, with additional support provided by the Mid-Atlantic Nutrition and Obesity Research Center (P30 DK072488), and the Office of Research and Development, Medical Research Service, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs. Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the NIH to the Johns Hopkins University (contract no. HHSN268200782096C). Assistance with data cleaning was provided by the GENEVA Coordinating Center (U01 HG 004446; PI Bruce S. Weir). Study recruitment and assembly of datasets were supported by a Cooperative Agreement with the Division of Adult and Community Health, Centers for Disease Control and Prevention, and by grants from NINDS and the NIH Office of Research on Women's Health (R01 NS45012, U01 NS069208-01). HPS: Heart Protection Study (HPS) (ISRCTN48489393) was supported by the UK MRC, British Heart Foundation, Merck and Co. (manufacturers of simvastatin), and Roche Vitamins Ltd. (manufacturers of vitamins). Genotyping was supported by a grant to Oxford University and CNG from Merck and Co. J.C.H. acknowledges support from the British Heart Foundation (FS/14/55/30806). ISGS: Ischemic Stroke Genetics Study (ISGS)/Siblings With Ischemic Stroke Study (SWISS) was supported in part by the Intramural Research Program of the NIA, NIH project Z01 AG-000954-06. ISGS/SWISS used samples and clinical data from the NIH-NINDS Human Genetics Resource Center DNA and Cell Line Repository (ccr.coriell.org/ninds), human subjects protocol nos. 2003-081 and 2004-147. ISGS/SWISS used stroke-free participants from the Baltimore Longitudinal Study of Aging (BLSA) as controls. The inclusion of BLSA samples was supported in part by the Intramural Research Program of the NIA, NIH project Z01 AG-000015-50, human subjects protocol no. 2003-078. The ISGS study was funded by NIH-NINDS Grant R01 NS-42733 (J.F.M.). The SWISS study was funded by NIH-NINDS Grant R01 NS-39987 (J.F.M.). This study used the high-performance computational capabilities of the Biowulf Linux cluster at the NIH (biowulf.nih.gov). MGH-GASROS: MGH Genes Affecting Stroke Risk and Outcome Study (MGH-GASROS) was supported by NINDS (U01 NS069208), the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research 0775010N, the NIH and NHLBI's STAMPEED genomics research program (R01 HL087676), and a grant from the National Center for Research Resources. The Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research resources. Milan: Milano–Besta Stroke Register Collection and genotyping of the Milan cases within CEDIR were supported by the Italian Ministry of Health (grant nos.: RC 2007/LR6, RC 2008/LR6; RC 2009/LR8; RC 2010/LR8; GR-2011-02347041), FP6 LSHM-CT-2007-037273 for the PROCARDIS control samples. WTCCC2: Wellcome Trust Case-Control Consortium 2 (WTCCC2) was principally funded by the Wellcome Trust, as part of the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z and WT084724MA). The Stroke Association provided additional support for collection of some of the St George's, London cases. The Oxford cases were collected as part of the Oxford Vascular Study, which is funded by the MRC, Stroke Association, Dunhill Medical Trust, National Institute of Health Research (NIHR), and the NIHR Biomedical Research Centre, Oxford. The Edinburgh Stroke Study was supported by the Wellcome Trust (clinician scientist award to C.L.M.S.) and the Binks Trust. Sample processing occurred in the Genetics Core Laboratory of the Wellcome Trust Clinical Research Facility, Western General Hospital, Edinburgh. Much of the neuroimaging occurred in the Scottish Funding Council Brain Imaging Research Centre (https://www.ed.ac.uk/clinical-sciences/edinburgh-imaging), Division of Clinical Neurosciences, University of Edinburgh, a core area of the Wellcome Trust Clinical Research Facility, and part of the SINAPSE (Scottish Imaging Network: A Platform for Scientific Excellence) collaboration (sinapse.ac.uk), funded by the Scottish Funding Council and the Chief Scientist Office. Collection of the Munich cases and data analysis was supported by the Vascular Dementia Research Foundation. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreements no. 666881, SVDs@target (to M.D.) and no. 667375, CoSTREAM (to M.D.); the DFG as part of the Munich Cluster for Systems Neurology (EXC 1010 SyNergy) and the CRC 1123 (B3) (to M.D.); the Corona Foundation (to M.D.); the Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain) (to M.D.); the e:Med program (e:AtheroSysMed) (to M.D.) and the FP7/2007-2103 European Union project CVgenes@target (grant agreement no. Health-F2-2013-601456) (to M.D.). M.F. and A.H. acknowledge support from the BHF Centre of Research Excellence in Oxford and the Wellcome Trust core award (090532/Z/09/Z). VISP: The GWAS component of the Vitamin Intervention for Stroke Prevention (VISP) study was supported by the US National Human Genome Research Institute (NHGRI), grant U01 HG005160 (PI Michèle Sale and Bradford Worrall), as part of the Genomics and Randomized Trials Network (GARNET). Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the NIH to Johns Hopkins University. Assistance with data cleaning was provided by the GARNET Coordinating Center (U01 HG005157; PI Bruce S. Weir). Study recruitment and collection of datasets for the VISP clinical trial were supported by an investigator-initiated research grant (R01 NS34447; PI James Toole) from the US Public Health Service, NINDS, Bethesda, MD. Control data obtained through the database of genotypes and phenotypes (dbGAP) maintained and supported by the United States National Center for Biotechnology Information, US National Library of Medicine. WHI: Funding support for WHI-GARNET was provided through the NHGRI GARNET (grant no. U01 HG005152). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GARNET Coordinating Center (U01 HG005157). Funding support for genotyping, which was performed at the Broad Institute of MIT and Harvard, was provided by the GEI (U01 HG004424). R.L. is a senior clinical investigator of FWO Flanders. F.W.A. is supported by a Dekker scholarship-Junior Staff Member 2014T001–Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre.