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Object Investigators conducting the International Study of Unruptured Intracranial Aneurysms, sponsored by the National Institutes of Health, sought to evaluate predictors of future hemorrhage in patients who had unruptured mirror aneurysms. These paired aneurysms in bilateral arterial positions mirror each other; their natural history is unknown. Methods Centers in the US, Canada, and Europe enrolled patients for prospective assessment of unruptured intracranial aneurysms. Central radiological review confirmed the presence or absence of mirror aneurysms in patients without a history of prior subarachnoid hemorrhage (SAH) (Group 1). Outcome at 1 and 5 years and aneurysm characteristics are compared. Results Of 3120 patients with aneurysms treated in 61 centers, 376 (12%) had mirror aneurysms, which are more common in women than men (82% [n = 308] vs 73% [n = 1992], respectively; p Compared with patients with nonmirror saccular aneurysms, a greater percentage of patients with mirror aneurysms had larger (>10 mm) aneurysms (mean maximum diameter 11.7 vs 10.4 mm, respectively; p Conclusions Overall, patients with mirror aneurysms were more likely to be women, to report a family history of aneurysmal SAH, and to have larger aneurysms. The presence of a mirror aneurysm was not an independent predictor of future SAHs.

Urban forests provide essential functions in support of human communities; however, studies indicate adjacent residential land uses degrade urban forests following development. The resulting impacts are known as encroachment. Local Ontario governments rely primarily on passive management, such as boundary structures (e.g. fences) to limit this degradation but do not know whether they are effective for limiting the area of the forest floor covered by these impacts. Transect and quadrat sampling of 40 forest edges adjacent to 186 residential properties were sampled in six Southern Ontario municipalities to determine impact frequency and area cover of encroachment. The results indicated some structures are effective in reducing the frequency and area cover of some encroachment behaviours. Other behaviours were not significantly reduced by any structural treatment. Furthermore, some behaviours were increased by structures. Substantial areas of encroachment continued to occur under even the most effec...

Pancreatic adenocarcinoma is mostly fatal and generally resistant to conventional treatments, such that effective therapies with tolerable side effects are desperately needed. Ion channels including the transient receptor potential (TRP) channels have been implicated in human malignancies, but their roles in pancreatic cancer were mostly unknown. Recent identification of the melastatin-subfamily members of the TRP family of ion channels, and their functions in pancreatic epithelia and adenocarcinoma, is expected to provide a new perspective to understanding the mechanism underlying pancreatic tumorigenesis. In this report, we present the clinical and pathological features of a mini-series of patients with pancreatic adenocarcinoma, which aberrantly exhibits immunoreactivity against the TRPM8 channel. We have recently demonstrated the proliferative role of TRPM8 channel in pancreatic cancer cells. Here, we present evidence that RNA interference-mediated silencing of TRPM8 induces replicative senescence in pancreatic adenocarcinoma cells. This suggests that the aberrantly expressed TRPM8 channel may contribute to pancreatic tumorigenesis by preventing oncogene-induced senescence, and targeted inhibition of TRPM8 may enhance tumor sensitivity to therapeutics. Based on these observations, we hypothesize that the TRPM8 ion channel plays a crucial role in the growth and progression of pancreatic neoplasia during tumorigenesis. We propose that TRPM8 can be exploited as a clinical biomarker and as a therapeutic target for developing personalized therapy in pancreatic adenocarcinoma.

Primary vasculitis of the central nervous system (PCNSV) is a rare and diagnostically challenging form of vasculitis limited to the brain and/or spinal cord. It is a complex and often severe disease with multifaceted clinical and pathological appearances, suggesting multiple disease subtypes and the potential existence of multiple etiologic pathways. We describe in detail the clinical, imaging, and neuropathological findings of PCNSV summarizing literature data and our observations from a cohort of 131 patients diagnosed at Mayo Clinic over a 25-year period (1983-2007). Unlike systemic vasculitis, little is known regarding PCNSV pathogenesis and the involved immunological mechanisms. Increased recognition of the disease spectrum and in-depth characterization of its histopathologic and immunological phenotype will be critical to eventually understanding the underlying derangements and mechanisms driving PCNSV. Improved understanding of the pathogenetic mechanisms of the disease may also help determine whether the different histologic patterns and clinical subsets represent more than one disease and ultimately may permit development of novel diagnostic and therapeutic strategies for it.

Studies increasingly document degradation and loss of publicly owned urban forest area following adjacent development due to residential encroachment. Little is known about prevailing approaches for limiting these impacts. Taking Southern Ontario as a case study, long interviews were conducted among Ontario planners, landscape architects, forest managers and bylaw officials within six Ontario municipalities to determine prevailing goals, tools, and strategies for addressing residential encroachment. Few municipalities had explicit goals, and none had objectives for addressing encroachment. Bylaws were the primary tools for addressing existing encroachments, but field studies indicated infrequent enforcement. Boundary-focused structures, such as fences, were the primary means of preventing encroachment; however, they were applied to a minority of forests with adjacent housing. None of the municipalities had a strategy for implementing their tools to protect targeted ecological, social or economic services provided by urban forests. Recommendations for improved approaches for managing residential encroachment impacts within forest edges are provided.

Purpose of review The aim of this review was to cover the recent major advances made in the fields of clinical assessment, diagnosis and treatment of adult primary central nervous system vasculitis (PCNSV). Recent findings To prevent misdiagnosis, particularly with the reversible cerebral vasoconstriction syndromes, new criteria on the basis of the levels of certainty of the diagnosis of PCNSV have been proposed. Advances in the neuroimaging techniques visualizing the wall of intracranial blood vessels have improved the capacity to distinguish inflammatory from noninflammatory vascular lesions. These techniques could play in the future an important role in the diagnosis of PCNSV. Studies of larger numbers of cases have revealed a more varied histopathological inflammatory picture and disclosed an association with amyloid angiopathy. It has also been recognized that PCNSV is a heterogeneous disorder encompassing clinical subsets that differ in terms of prognosis and therapy. Finally, differently from earliest reports that suggested a poor prognosis with a fatal outcome in the majority of the cases, a large recent study from Mayo Clinic has described a more favorable course with good response to therapy and a favorable outcome in 81% of cases. Summary Our better understanding of the PCNSV spectrum and its subsets will facilitate early recognition. This may facilitate earlier treatment and may prevent irreversible or even lethal outcomes.

Ischemic stroke (IS) is among the leading causes of death in Western countries. There is a significant genetic component to IS susceptibility, especially among young adults. To date, research to identify genetic loci predisposing to stroke has met only with limited success. We performed a genome-wide association (GWA) analysis of early-onset IS to identify potential stroke susceptibility loci. The GWA analysis was conducted by genotyping 1 million SNPs in a biracial population of 889 IS cases and 927 controls, ages 15–49 years. Genotypes were imputed using the HapMap3 reference panel to provide 1.4 million SNPs for analysis. Logistic regression models adjusting for age, recruitment stages, and population structure were used to determine the association of IS with individual SNPs. Although no single SNP reached genome-wide significance (P < 5 × 10−8), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P = 1.2 × 10−7) and rs1986743 (in ARL6IP6; P = 2.7 × 10−7), strongly associated with early-onset stroke. These data suggest that a novel locus on human chromosome 2q23.3 may be associated with IS susceptibility among young adults.

Background and objectives Autosomal dominant polycystic kidney disease (ADPKD) patients have an increased risk for intracranial aneurysms (IAs). The importance of screening for unruptured IAs (UIAs) depends on their risks for growth and rupture. Design, setting, participants, & measurements ADPKD patients with UIAs found by presymptomatic screening with magnetic resonance angiography (MRA) during 1989 to 2009 were followed initially at 6 months and annually, and less frequently after demonstration of stability. Results Forty-five saccular aneurysms were detected in 38 patients from 36 families. Most were small (median diameter 3.5 mm) and in the anterior circulation (84%). Median age at diagnosis was 49 years. During cumulative imaging follow-up of 243 years, one de novo UIA was detected and increased in size from 2 to 4.4 mm over 144 months and two UIAs grew from 4.5 to 5.9 mm and 4.7 to 6.2 mm after 69 and 184 months, respectively. Seven patients did not have imaging follow-up. No change was detected in the remaining 28 patients. During cumulative clinical follow-up of 316 years, no aneurysm ruptured. Five patients died from unrelated causes and two were lost to follow-up after 8 and 120 months. Three patients underwent surgical clipping. Conclusions Most UIAs detected by presymptomatic screening in ADPKD patients are small and in the anterior circulation. Growth and rupture risks are not higher than those of UIAs in the general population. These data support very selective screening for UIAs in ADPKD patients, and widespread screening is not indicated.

Background and Purpose— Coronary artery disease is the leading cause of death after TIA. Reliable estimates of the risk of MI after TIA, however, are lacking. Methods— Our purpose was to determine the incidence of and risk factors for MI after TIA. We cross-referenced preexisting incidence cohorts from the Rochester Epidemiology Project for TIA (1985–1994) and MI (1979–2006) to identify all community residents with incident MI after incident TIA. Incidence of MI after TIA was determined using Kaplan–Meier life-table methods. This was compared to the age-, sex-, and period-specific MI incidences in the general population. Proportional hazards regression analysis was used to examine associations between clinical variables and the occurrence of MI after TIA. Results— Average annual incidence of MI after TIA was 0.95%. Relative risk for incident MI in the TIA cohort compared to the general population was 2.09 (95% CI, 1.52–2.81). This was highest in patients younger than 60 years old (relative risk, 15.1; 95% CI, 4.11–38.6). Increasing age (hazard ratio, 1.51 per 10 years; 95% CI, 1.14–2.01), male sex (hazard ratio, 2.19; 95% CI, 1.18–4.06), and the use of lipid-lowering therapy at the time of TIA (hazard ratio, 3.10; 95% CI, 1.20–8.00) were independent risk factors for MI after TIA. Conclusions— Average annual incidence of MI after TIA is ≈1%, approximately double that of the general population. The relative risk increase is especially high in patients younger than 60 years old. These data are useful for identifying subgroups of patients with TIA at highest risk for subsequent MI.

Pit and quarry sites from sand, gravel, and rock extraction must be rehabilitated by law in Ontario. Adjacent and nearby landscapes affect local residents' perceptions of the success of rehabilitation in terms of how the former extraction site "fits" the landscape. Along with ecological imperatives, the ways in which rehabilitation is designed to fit a social landscape warrants investigation. It would benefit local people, the aggregates industry, rehabilitation designers, and policy makers to have more information about how rehabilitation projects can embrace local ecological and social contexts by considering how people might perceive the acceptability and cultural value of a rehabilitation. We explored this question in southern Ontario using an online questionnaire to gather responses to a series of photographs, some of which were simulated, showing a range of landscape conditions that might occur around pits and quarries. Respondents were considerably concerned with forest loss, and to a lesser degree with habitats like wetlands and streams. Though housing perceived to be suburban was disliked, housing clusters in a rural area did not suffer the same result. People did not consistently choose a single focus as most desirable. Instead they responded to attributes within the context in which the rehabilitation occurred.

We present an unusual case of a single gunshot to the genitalia in which the bullet trajectory injured the urethra, corpus cavernosum, and both testicles. All injuries were successfully repaired during initial exploration. Our report serves as a reminder to clinicians to have a high index of suspicion in this circumstance and consider immediate exploration of all the injured areas. We also demonstrate the use of a dartos fascia interposition flap to cover and separate the concomitant urethral and corporal sutures lines. Our dartos flap bolstered the urethral and cavernosal repairs and helped prevent postoperative corporourethral fistula formation.

White matter hyperintensity (WMH) may be a marker of an underlying cerebral microangiopathy. Therefore, we hypothesized that WMH would be most severe in patients with lacunar stroke and intracerebral hemorrhage (ICH), 2 types of stroke in which cerebral small vessel (SV) changes are pathophysiologically relevant.We determined WMH volume (WMHV) in cohorts of prospectively ascertained patients with acute ischemic stroke (AIS) (Massachusetts General Hospital [MGH], n = 628, and the Ischemic Stroke Genetics Study [ISGS], n = 263) and ICH (MGH, n = 122).Median WMHV was 7.5 cm³ (interquartile range 3.4-14.7 cm³) in the MGH AIS cohort (mean age 65 ± 15 years). MGH patients with larger WMHV were more likely to have lacunar stroke compared with cardioembolic (odds ratio [OR] = 1.87 per SD normally transformed WMHV), large artery (OR = 2.25), undetermined (OR = 1.87), or other (OR = 1.85) stroke subtypes (p0.03). These associations were replicated in the ISGS cohort (p = 0.03). In a separate analysis, greater WMHV was seen in ICH compared with lacunar stroke (OR = 1.2, p0.02) and in ICH compared with all ischemic stroke subtypes combined (OR = 1.34, p0.007).Greater WMH burden was associated with SV stroke compared with other ischemic stroke subtypes and, even more strongly, with ICH. These data, from 2 independent samples, support the model that increasing WMHV is a marker of more severe cerebral SV disease and provide further evidence for links between the biology of WMH and SV stroke.

Intracranial aneurysms (IAs) are acquired lesions, with a genetic predisposition in selected patients. They are very common in the population, occurring in ~2% of people in the United States. Intracranial aneurysms may present with subarachnoid hemorrhage, the most feared complication of IA, but most commonly they are detected on brain imaging performed for reasons unrelated to the IA. Once detected, the key question is whether the unruptured intracranial aneurysm needs to be treated, or can safely be left alone. This decision is complex and is dependent on numerous factors, including the natural history of the unruptured intracranial aneurysm, in comparison to the risk of unruptured intracranial aneurysm treatment. For those not treated with interventional treatment, repeat imaging at some intermittency may be recommended. In this article, the data regarding the natural history of unruptured intracranial aneurysm and the procedure-associated morbidity and mortality are reviewed, as well as the predictors of hemorrhage, and the likelihood of unruptured intracranial aneurysm growth should conservative management with intermittent repeat imaging be recommended.

To explore the implications of surrounding landscape context on the ecological effects of rehabilitation, we assessed three alternative ways of rehabilitating depleted Ontario sites with measures of habitat patterns and cumulative costs (landscape resistance). Alternative rehabilitations focused on (a) economics, (b) biodiversity protection and (c) a compromise of economics and biodiversity. We measured the landscape effects of the different rehabilitations within a 10 km radius of several depleted aggregate sites. A cost-surface model showed that the biodiversity protection alternative achieved lower landscape resistance than the other alternatives, and importantly that this effect could extend well beyond the site. Measuring four attributes of landscape pattern the differences among alternatives showed that the biodiversity alternative offered the best habitat patterns over the economic alternative. Yet for some sites a compromise alternative could achieve similar ecological consequences while balancing...

Studies have identified that, given the opportunity, the majority of North Americans would prefer to live in small towns and rural areas. This preference is based in aesthetic notions linked to landscape features, personal meaning, and perceptions. In order to understand how the growing non-farm rural landowner population will influence the rural landscape, this research explored the motivations of non-farm rural landowners for living in rural areas, and their perceptions of their property. It involved five preliminary focus groups with farm and non-farm landowners owning land in rural, urbanising rural, and urbanised rural areas, and four final focus groups. The research also included a survey of 944 landowners in Southern Ontario. People choose to live in rural areas because they are quiet, natural, open, private, and clean. In contrast, people chose to buy their properties for very practical reasons: location, cost, availability and quality of resources, and size. Results suggest that non-farm...

Natural systems play important ecological, social and economic functions within suburban environments, such as wildlife habitat, community recreation and stormwater management. However, their integrity is at risk if there is encroachment into these systems from adjacent land uses. Local governments often consider active management of natural systems too expensive, so rely on structural approaches, such as fences, to manage the physical interface between housing land uses and natural systems. Despite a reliance on this approach, it is not known whether it is effective in protecting natural systems from these impacts. Research has identified spatial extent of disturbance as a key measure of human impact on forested natural systems, and planners want to know how far adjacent land use impacts extend into the forest edge to specify protective buffer strips between these land uses. This study measured the extent of post development impacts of over 350 residences built adjacent to suburban forests in Southern Ontario. The results indicate that boundary treatments can offer some long-term protection from residential encroachment; however, commonly implemented treatments can be greatly improved based on the results of this study. Boundaries between residences and natural systems should be carefully designed to control physical access, clearly delineate private from public land uses, and where appropriate, encourage community monitoring of the housing/forest interface. However, even under the most effective boundary treatment, encroachment activities continued at significant distances from forest borders. Forested buffers of at least 50 m wide are required to segregate encroachment impacts from sensitive forested natural systems.

Wafer-to-wafer bonding is widely used to support both the production of integrated circuits and MEMS devices. Bonding may be accomplished in a variety of ways including anodic, thermal compression, and adhesive bonding. The bond may be either permanent or temporary. Permanent wafer bonding is used to combine two materials together that remain together for the life of the device, for example, in the production of Si/GaAs wafer heterostructures for integration of an optoelectronic device into silicon integrated circuit technology. Temporary bonding is used to support the device wafer during certain processing steps, and then removed once the device wafer is completed. Currently, there are several temporary bonding processes being developed in industry. The leading technology utilizes some form of polymeric material to temporarily fasten or bond a rigid backing material, usually silicon or glass, to the device wafer for processing. The main issues associated with these techniques are temperature stability of the adhesive, removal from the support wafer, and cleaning the adhesive from the device wafer. The ideal process would require bonding at an acceptable temperature (usually less than 200°C), surviving through higher temperature processes, followed by debonding at lower temperature or even room temperature. In this paper, an alternative solution is reported that utilizes current thermoplastic adhesives and silicon support wafers coupled with a patented technology, developed by Brewer Science, Inc. Support wafers are bonded to device wafers at acceptable temperatures, mechanical integrity is maintained through semiconductor or MEMs processing, and the completely processed device wafer is then safely debonded from the support wafer at room temperature.

We sought to examine the relationship of the QTc interval with mortality and functional outcome after acute ischemic stroke, and determine whether a threshold cutoff is present beyond which risk of death increases.The QTc interval was measured for all patients presenting to the emergency department. The outcomes were mortality at 90 days and functional outcome at hospital discharge. The cutoffs were determined plotting martingale residuals.Patients with a prolonged QTc interval were more likely to die within 90 days compared with patients without a prolonged interval (relative risk [RR] 2.5; 95% confidence interval [CI] 1.5-4.1; P.001). The estimated survival at 90 days was 70.5% and 87.1%, respectively. This association retained statistical significance after adjusting for age and National Institutes of Health Stroke Scale score (RR 1.7; 95% CI 1.0-2.9; P = .043). Patients with a prolonged QTc interval were also more likely to have poor functional status compared with patients without a prolonged interval (odds ratio 1.8; 95% CI 1.2-3.0; P = .006). This association was not statistically significant after adjusting for age and National Institutes of Health Stroke Scale score (odds ratio 1.2; 95% CI 0.7-2.4). The identified threshold cutoffs for increased risk of death at 90 days were 440 milliseconds for women and 438 milliseconds for men.There appears to be an increased risk of early death in patients with acute ischemic stroke and a prolonged QTc interval at the time of emergency department presentation. Prognosis appears to be worse with QTc intervals longer than 440 milliseconds in women and longer than 438 milliseconds in men.

Methodological and political issues arise during the designing, conducting, and reporting of campus-climate studies for LGBT students. These issues interact; making a decision about a methodological issue (e.g., sample size) has an impact on a political issue (e.g., how well the findings will be received). Ten key questions that must be addressed when planning an LGBT campus climate study are identified and different approaches investigators have taken when conducting studies are described. Additionally, the article provides tips for being sensitive to institutional needs and vulnerabilities, as well as being responsive to methodological and political issues.

Background The Joint Commission (JC) certifies primary stroke centers in the United States. Whether certification promotes enrollment of study subjects into stroke research studies is not known. We examined whether enrollment performance of centers was related to JC certification status. Methods The 51 US Siblings with Ischemic Stroke Study (SWISS) centers were characterized by JC certification status, year of certification, year initiated into SWISS, center location, and whether the center had a vascular/stroke neurology fellowship program accredited by the Accreditation Council for Graduate Medical Education. Performance measures included days elapsed from initiation to first enrollment, total enrollments within 12 months after initiation, and annual rate of enrollment thereafter. Results In all, 36 of 51 SWISS sites (71%) were JC certified. A total of 32 (63%) were initiated into the study from 2000 through 2002, and 19 (37%) were initiated from 2005 through May 2008. Comparison of certified and noncertified sites showed no significant difference in the time to first enrollment (median, 77.5 v 115 days; P = .90), total enrollees in the first year (median, 3 v 2 probands; P = .69), or annual enrollment rate (median, 1.9 v 1.8 probands; P = .72). The rate of enrollment or time to first enrollment was not different between 2000-to-2002 and 2005-to-2008 sites. Early-initiated centers tended to have better year-1 enrollment than later-initiated centers (3 v 2 probands; P = .056). Conclusions JC certification did not have a significant effect on SWISS center enrollment. The JC should encourage the research mission among certified stroke centers.

Background and Purpose— Transient ischemic attacks are a frequent diagnosis in the emergency department setting, yet expert opinion as to the proper follow-up and need for hospitalization differs widely. Recently, an effort has been made to risk-stratify patients presenting with transient ischemic attacks through scoring systems such as the ABCD and ABCD2 scales. The aim of our study was to independently validate these scores using a population-based cohort. Methods— Using the data from the Rochester Stroke and Transient Ischemic Attack Registry and resources of the Rochester Epidemiology Project, medical records of all residents of Rochester, Minn, with a diagnosis of incident transient ischemic attack from 1985 through 1994 were examined (N=284). Patients were scored on the ABCD and ABCD2 scales and new scores were created by adding hyperglycemia and a history of hypertension. The end points of stroke and death were collected previously and were verified through the Rochester Epidemiology Project data. Results— Although our study did find that scores >4 had a statistically significant predictive value for future stroke, a substantial proportion of strokes within 7 days (9 of 36 cases [25%]) occurred in patients with low or intermediate risk scores (≤4) on the ABCD2 scale. Including history of hypertension and hyperglycemia on presentation increased the sensitivity of the score to identify patients who had a stroke within 7 days. Conclusions— Reliance on the ABCD and ABCD2 scores misses some patients who will have a stroke within 7 days of a transient ischemic attack. Adding hyperglycemia and a history of hypertension to the predictive model could be useful, but the value of these additions need to be evaluated further.

Background and Purpose— The risk of intracranial aneurysm (IA) rupture in asymptomatic members of families who have multiple affected individuals is not known. Methods— First-degree unaffected relatives of those with a familial history of IA who had a history of smoking or hypertension but no known IA were offered cerebral MR angiography (MRA) and followed yearly as part of a National Institute of Neurological Diseases and Stroke-funded study of familial IA (Familial Intracranial Aneurysm [FIA] Study). Results— A total of 2874 subjects from 542 FIA Study families were enrolled. After study enrollment, MRAs were performed in 548 FIA Study family members with no known history of IA. Of these 548 subjects, 113 subjects (20.6%) had 148 IAs by MRA of whom 5 subjects had IA ≥7 mm. Two subjects with an unruptured IA by MRA/CT angiography (3-mm and 4-mm anterior communicating artery) subsequently had rupture of their IA. This represents an annual rate of 1.2 ruptures per 100 subjects (1.2% per year; 95% CI, 0.14% to 4.3% per year). None of the 435 subjects with a negative MRA have had a ruptured IA. Survival curves between the MRA-positive and -negative cohorts were significantly different ( P =0.004). This rupture rate of unruptured IA in the FIA Study cohort of 1.2% per year is approximately 17 times higher than the rupture rate for subjects with an unruptured IA in the International Study of Unruptured Aneurysm Study with a matched distribution of IA size and location 0.069% per year. Conclusions— Small unruptured IAs in patients from FIA Study families may have a higher risk of rupture than sporadic unruptured IAs of similar size, which should be considered in the management of these patients.

Objectives We sought to determine safety, recurrence rates, and novel risk factors for recurrence in patients with cryptogenic stroke/transient ischemic attack (TIA) after patent foramen ovale closure. Background Patent foramen ovale closure in patients with cryptogenic stroke/TIA remains highly controversial. There are limited data on long-term recurrence rates and their predictors in these patients. Methods The records of all patients who underwent patent foramen ovale device closure between December 2001 and June 2006 were reviewed. Patients were seen for clinical follow-up at 3 months then followed annually via telephone. Primary end points were recurrent stroke/TIA. Kaplan-Meier methods were used to estimate recurrent event rates. Cox regression analysis was used to identify risk factors for recurrences. Results There were 352 patients with cryptogenic stroke (n = 225) or TIA (n = 118) with a mean age of 53.4 years. The procedural complication rate was 3.4%. Recurrent events occurred in 8 patients: 7 strokes and 2 TIA, 1 patient had 2 recurrent strokes. The recurrence rate was 0.6% and 2.1% for stroke and 0.3% and 0.7% for TIA at 1 and 4 years, respectively. The combined end point of recurrent stroke/TIA occurred at a rate of 0.9% and 2.8% at 1 and 4 years, respectively. Risk factors for recurrences were elevated pulmonary artery pressure (hazard ratio [HR]: 1.12, p = 0.009), elevated right ventricular pressure (HR: 1.09, p = 0.04), factor V Leiden mutation (HR: 7.42, p = 0.014), and protein S deficiency (HR: 12.2, p = 0.002). Residual shunt and atrial septal aneurysm were not associated with recurrences. Conclusions Patent foramen ovale device closure is safe and is associated with a low recurrence of stroke/TIA. Factors associated with recurrence are thrombophilia and elevated intracardiac pressures.

The purpose of this paper is to improve the accuracy of the COMFA outdoor thermal comfort model for application to subjects performing physical activity. A sensitivity analysis was performed to identify conditions where the COMFA model produced erroneous estimates of the heat and moisture exchanges between the human body and the ambient environment, based on data from subjects performing moderate-to-vigorous physical activity. Errors occurred at high metabolic rates (> 400 W m–2), high wind speeds (> 4 m s–1) and warm air temperatures (> 28°C). Revisions to the clothing resistance (r c), clothing vapour resistance (r cυ), skin tissue resistance (r t), and skin temperature (T sk) equations were proposed. The revised assessment revealed that subjects had a wide range of thermal acceptability (B = −20 W m–2 to +150 W m–2), which was offset to the warm-end of the comfort scale. The revised model (COMFA*) performed well, predicting the actual thermal sensation of subjects in approximately 70% of cases. This study effectively integrated current empirical research related the effect of wind and activity on the clothing microclimate to improve the application of an outdoor thermal comfort model for subjects performing physical activity.

With the aging of the general population and the availability of noninvasive imaging studies, carotid artery stenosis is a disease commonly seen in general medical practice. Differentiation between symptomatic and asymptomatic disease is critical to the treatment course because the natural history differs markedly between them. Antiplatelet therapy and aggressive treatment of vascular risk factors are the mainstays of medical therapy. Class I evidence shows that carotid endarterectomy (CEA) is effective in preventing ipsilateral ischemic events in patients with symptomatic moderate- and high-grade stenosis. The procedure is also effective in selected patients with asymptomatic stenosis, but the benefit is marginal. In the past decade, carotid angioplasty and stenting has been proposed as a valid alternative to CEA. Currently, it is unclear whether carotid angioplasty and stenting is as safe as CEA in patients with carotid artery stenosis who need invasive treatment. Large clinical trials are under way to answer this question.

Background Statins have been shown to improve the functional outcome of patients after an ischemic stroke. We hypothesized that daily statin intake improves functional outcome after an acute ischemic stroke in patients with low-density lipoprotein (LDL) less than or equal to 100 mg/dL. Methods This was a prospective cohort study during a 22-month period of patients presenting with an acute ischemic stroke and lipid profiles measured. The functional disability was determined using modified Rankin scale score (0-2 good outcome, 3-6 bad outcome) at discharge. Chi-square test for binary data and nonparametric tests for nonnormally distributed variables were used for analysis. Results Of 508 patients, 207 presented with an LDL of 100 mg/dL or less and were included in the analysis. There was no significant difference in admission stroke severity (National Institutes of Health Stroke Scale [NIHSS]; P = .18), age ( P = .31), and sex ( P = .06) between those taking statins and not taking statins. Patients with LDL less than or equal to 100 mg/dL and taking statins (n = 100) were significantly more likely to have a good functional outcome (odds ratio 1.91; 95% confidence interval 1.05-3.47) when compared with those not on the medication. After adjusting for age, sex, and NIHSS, statin intake still predicted a better functional outcome ( P Conclusion Daily statin intake appears to result in a better functional outcome after an ischemic stroke in patients with ideal LDL levels (≤100 mg/dL) before and after adjusting for age and stroke severity. Pleiotropic effects of statins may play a role in this.

Background and Purpose— Size of an unruptured intracranial aneurysm (UIA) may be an important risk factor for rupture. Accordingly, serial noninvasive imaging is commonly used to assess untreated UIA for enlargement. Few data exist regarding the frequency and predictors of enlargement. We obtained this information from a group of patients followed with serial MR angiography (MRA). Methods— We retrospectively identified 165 patients with 191 UIA followed with serial MRA. Fusiform aneurysms, UIA Results— Twenty aneurysms (10%) grew over a median follow-up period of 47 months. Frequency of enlargement was 6.9%, 25%, and 83% for aneurysms P Conclusions— Over a median follow-up period of 47 months, 10% of UIA enlarged. Larger aneurysms had a significantly increased risk of enlargement. The likelihood of enlargement was highest in aneurysms with diameters ≥8 mm. However, a clinically significant proportion of small aneurysms grow, and this growth can be detected by serial MRA.

Background and Purpose— Risk for both intracranial aneurysms (IAs) and aortic aneurysms (AAs) is thought to be heritable with mounting evidence for genetic predisposition. The concept of shared risk for these conditions is challenged by differences in age of diagnosis and demographic characteristics. We performed a genomewide linkage analysis in multiplex families with both IA and AA from the Familial Intracranial Aneurysm study. Methods— Available medical records of subjects who reported IA or abdominal/thoracic AA were reviewed with adjudication as definite/probable, possible, or not a case. To identify genes contributing to the susceptibility for IA and AA, genomewide linkage analysis was performed in the 26 multiplex IA families who had members who also had thoracic or abdominal AA. Individuals (n=91) were defined as affected if they had an IA (definite/probable) or an aortic or thoracic AA (definite/probable). Results— Maximum logarithm of odds (LOD) scores were found on chromosomes 11 (144 cM; LOD=3.0) and 6 (33 cM; LOD=2.3). In both chromosomal regions, analyses of these same 26 families considering only IA as the disease phenotype produced LOD scores of 1.8 and 1.6, respectively. Conclusions— Our linkage analysis in these 26 families using the broadest disease phenotype, including IA, abdominal AA, and thoracic AA, supports the concept of shared genetic risk. The chromosome 11 locus appears to confirm earlier independent associations in IA and AA. The chromosome 6 finding is novel. Both warrant further investigation.

Objective: To assess stroke awareness among patients presenting to the emergency department with an acute ischaemic stroke or transient ischaemic attack (TIA). Methods: A consecutive cohort of patients presenting with a cerebrovascular event was prospectively enrolled over a 15-month period and questionnaires were administered. If the patient was unable to respond to the questions or answer the questionnaire, it was administered to the primary caregiver. Comprehension of having a cerebrovascular event, reason for delay in presentation, mode of arrival and knowledge of treatment modalities were determined. Results: Only 42% of 400 patients thought they were having a stroke or TIA. The median time to presentation was 3.4 h. Delayed presentation was almost equal in men and women. When asked about onset, 19.4% thought that a stroke came on gradually and only 51.9% thought immediate presentation was crucial. 20.8% of patients had heard of thrombolysis. Conclusion: Community knowledge of ischaemic stroke needs to be enhanced so that individuals present earlier, leading to timely management.

Object Approximately 20% of patients with an intracranial saccular aneurysm report a family history of intracranial aneurysm (IA) or subarachnoid hemorrhage. A better understanding of predictors of aneurysm detection in familial IA may allow more targeted aneurysm screening strategies. Methods The Familial Intracranial Aneurysm (FIA) study is a multicenter study, in which the primary objective is to define the susceptibility genes related to the formation of IA. First-degree relatives (FDRs) of those affected with IA are offered screening with magnetic resonance (MR) angiography if they were previously unaffected, are ≥ 30 years of age, and have a history of smoking and/or hypertension. Independent predictors of aneurysm detection on MR angiography were determined using the generalized estimating equation version of logistic regression. Results Among the first 303 patients screened with MR angiography, 58 (19.1%) had at least 1 IA, including 24% of women and 11.7% of men. Ten (17.2%) of 58 affected patients had multiple aneurysms. Independent predictors of aneurysm detection included female sex (odds ratio [OR] 2.46, p = 0.001), pack-years of cigarette smoking (OR 3.24 for 20 pack-years of cigarette smoking compared with never having smoked, p < 0.001), and duration of hypertension (OR 1.26 comparing those with 10 years of hypertension to those with no hypertension, p = 0.006). Conclusions In the FIA study, among the affected patients' FDRs who are > 30 years of age, those who are women or who have a history of smoking or hypertension are at increased risk of suffering an IA and should be strongly considered for screening.

The landscape has a dramatic effect on a site’s ecological and social function. Landscape context and pattern are important considerations in ecological restoration for their effects on rehabilitation design and ecological function. In Ontario, Canada, there are more than 5,300 active aggregate mining sites, equivalent to a total area of over 70 square kilometers. Rehabilitation of inactive pits is required by law, but rehabilitation efforts rarely attempt to restore ecological function to a site, and even more rarely consider the ecological implications of landscape context. The size, spatial extent, and nonrandom distribution of aggregate extraction sites in Ontario offer opportunities to restore ecological functions through cooperative rehabilitation, where landowners and licensed aggregate extractors try to achieve better ecological outcomes. In order to illustrate how landscape context can make a meaningful contribution to rehabilitation design and ecological restoration of pit and quarry sites in Ontario and in other settings, we review methods of assessing critical aspects of landscape context, including patterns of habitats (mosaics), interpatch movements and dispersal (connectivity and permeability), and the heterogeneity of microclimates (niche diversity). We illustrate the potential of this approach with the example of the Karner blue butterfly. The described project may inform restoration approaches for other land uses and landscape contexts.

We expand on previous literature on party competition in the American states by examining competition for both state and national offices. We find significant differences in Democratic Party electoral advantage within states, along with across-state variation in changes in these differences over time. We attribute these results to movement in the partisanship and ideology of the states' citizenry. As consistency in these core political attitudes increases, parties are able to campaign and govern on messages that are more consistent across electoral levels. The result is greater consistency in party electoral performance across state and national offices.

To determine if differences in outcome exist between diabetic and non-diabetic patients who present to the Emergency Department (ED) with acute ischemic stoke (AIS) and elevated blood glucose. The study population consisted of 447 consecutive patients who presented to the ED with AIS within 24 h of symptom onset and had blood glucose measured on presentation. Hyperglycemia was defined as >130 mg/dl. Outcomes studied included infarct volume, stroke severity (NIH Stroke Scale), functional impairment (modified Rankin Score), and 90-day mortality. Patients with hyperglycemia were then stratified into those with and without a prior history of diabetes mellitus (DM) for the purposes of analysis. Patients with hyperglycemia exhibited significantly greater stroke severity (P = 0.002) and greater functional impairment (P = 0.004) than those with normoglycemia. Patients with hyperglycemia were 2.3 times more likely to be dead at 90 days compared to those with normal glucose (P

Workflow solutions driven by data pipelining are increasingly becoming popular for accessing, aggregating and analyzing disparate data to make informed and intelligent decisions. Uses of workflow technologies which facilitate business intelligence (BI) improve productivity, decision making and research efficiency. In order to provide BI in a scientific or clinical based organization, it is imperative that the application or workflow technology must be compatible with multiple data types and formats, be able to analyze the data and make it available throughout the organization. We term this as Scientific Business Intelligence (SBI) and discuss how modeling, simulations and informatics software, integrated with open and standards-based scientific operating platform (SOP), can deliver scientifically-relevant BI solutions. We illustrate SBI with several examples encompassing all levels of users within an organization.

Background and Purpose— The extent of potential consent bias in observational studies elucidating genetic and environmental contributions to ischemic stroke is largely unknown. The purpose of this study was to assess differences in stroke cohort characteristics between those who provided informed consent and those whose enrollment was authorized by surrogate decision makers. Methods— The Ischemic Stroke Genetics Study (ISGS) is a prospective, 5-center, case-control study of first-ever ischemic stroke. Demographic, clinical, and stroke characteristics were compared between cases enrolled by self versus by surrogate. Data from one site that limits enrollment only to those able to self-consent were also analyzed to compare those who enrolled with those not able to consent. Results— Overall, 10% (54 of 517) were enrolled using surrogate authorization. Self-consented and surrogate-authorized cases did not differ significantly in age, sex, or conventional risk factors. Surrogate-authorized cases had significantly more severe stroke deficits, larger infarcts, and infarcts localizing to left supratentorial regions. Similarly, at the site restricting enrollment, stroke severity and characteristics differed between self-consented individuals and those otherwise eligible but unable to provide consent. Conclusions— Failure to permit surrogate authorization in genetic studies of ischemic stroke may skew enrollment toward less severe strokes caused by smaller infarcts. This potential consent bias may undermine the ability to identify genetic determinants of risk and severity and suggests that surrogate enrollment in these studies can be ethically justifiable.

Objectives We sought to define thromboembolic risk after surgery for mitral regurgitation (MR), particularly ischemic stroke (IS) compared with the general population. Background Guidelines recommend surgery in asymptomatic patients with MR, but IS risks are unknown. Methods In 1,344 patients (age 65 ± 12 years) consecutively operated for MR (procedures: 897 mitral valve repair [MRep] and 447 valve replacement: 231 mechanical mitral valve replacement [MVRm], 216 biological mitral valve replacement [MVRb]), thromboembolic complications, particularly IS (diagnosed by neurologists), during follow-up were assessed early ( Results Ischemic stroke occurred in 130 patients: 1.9 ± 0.4% and 2.7 ± 0.5% at 30 days and 180 days, respectively, and 8.1 ± 0.8% at 5 years. We found that IS rates were lowest after MRep versus MVRb and MVRm (6.1 ± 0.9% vs. 8 ± 2.1%, and 16.1 ± 2.7% at 5 years, respectively, p 0.10 between procedures) and moderate risk at >30 days (risk ratio 1.7 overall; 1.3 for MRep; 0.98 for MVRb; 4.8 for MVRm). Beyond 180 days, IS risk declined further and was similar to the population for MRep (relative risk 1.2) and for MVRb (relative risk 0.9). Bleeding risk >30 days was lowest in MRep versus MVRb and MVRm (10-year risk 7 ± 1%, 14 ± 4%, and 16 ± 3%, respectively). Conclusions Thromboembolic complications after MR surgery are a reason for both concern and encouragement. The risk of IS is notable early, irrespective of procedure, but in the long term it is not greater than in the population after MRep and MVRb. Preference for MRep should be emphasized, and trials aiming at preventing IS should be conducted to reduce thromboembolic and hemorrhagic risk after surgery for MR.

Technological advances in molecular genetics allow rapid and sensitive identification of genomic copy number variants (CNVs). This, in turn, has sparked interest in the function such variation may play in disease. While a role for copy number mutations as a cause of Mendelian disorders is well established, it is unclear whether CNVs may affect risk for common complex disorders. We sought to investigate whether CNVs may modulate risk for ischemic stroke (IS) and to provide a catalog of CNVs in patients with this disorder by analyzing copy number metrics produced as a part of our previous genome-wide single-nucleotide polymorphism (SNP)-based association study of ischemic stroke in a North American white population. We examined CNVs in 263 patients with ischemic stroke (IS). Each identified CNV was compared with changes identified in 275 neurologically normal controls. Our analysis identified 247 CNVs, corresponding to 187 insertions (76%; 135 heterozygous; 25 homozygous duplications or triplications; 2 heterosomic) and 60 deletions (24%; 40 heterozygous deletions; 3 homozygous deletions; 14 heterosomic deletions). Most alterations (81%) were the same as, or overlapped with, previously reported CNVs. We report here the first genome-wide analysis of CNVs in IS patients. In summary, our study did not detect any common genomic structural variation unequivocally linked to IS, although we cannot exclude that smaller CNVs or CNVs in genomic regions poorly covered by this methodology may confer risk for IS. The application of genome-wide SNP arrays now facilitates the evaluation of structural changes through the entire genome as part of a genome-wide genetic association study.

The complexities of the interactions between long- and short-wave radiation fluxes and the human body make it inherently difficult to estimate precisely the total radiation absorbed (R) by a human in an outdoor environment. The purpose of this project was to assess and compare three methods to estimate the radiation absorbed by a human in an outdoor environment, and to compare the impact of applying various skin and clothing albedos (alpha ( h )) on R. Field tests were conducted under both clear and overcast skies to evaluate the performance of applying a cylindrical radiation thermometer (CRT), net radiometer, and a theoretical estimation model to predict R. Three albedos were evaluated: light (alpha ( h ) = 0.57), medium (alpha ( h ) = 0.37), and dark (alpha ( h ) = 0.21). During the sampling periods, the range of error between the methods used to estimate the radiation absorbed by a cylindrical body under clear and overcast skies ranged from 3 to 8%. Clothing and skin albedo had a substantial impact on R, with the mean change in R between the darkest and lightest albedos ranging from 115 to 157 W m( - 2) over the sampling period. Radiation is one of the most important variables to consider in outdoor thermal comfort research, as R is often the largest contributor to the human energy balance equation. The methods outlined and assessed in this study can be conveniently applied to provide reliable estimates of the radiation absorbed by a human in an outdoor environment.

Background: Epidemiologic studies suggest sex differences in evaluation of patients presenting with ischemic stroke. Sex differences in stroke evaluation could lead to sex differences in the validity of diagnosing ischemic stroke subtypes. This study assessed sex differences in the Ischemic Stroke Genetics Study (ISGS). Methods: The ISGS is a prospective case-control genetic association study of patients with first-ever ischemic stroke at 5 US tertiary stroke centers. The diagnostic tests performed as part of medical care were recorded for each enrolled patient. Results: A total of 505 patients were enrolled; 45% (229 of 505) were women and 55% (276 of 505) were men. Mean age at time of stroke was greater for women (66.6 v 61.9 years; P = .001). Frequency of brain computed tomography was 92% (254 of 276) for men and 90% (206 of 229) for women ( P = .42). Magnetic resonance imaging was completed in 84% (232 of 276) of men and 83% (191 of 229) of women ( P = .91). Frequency of electrocardiography was 91% (252 of 276) for men and 90% (206 of 229) for women ( P = .60). Echocardiography was done in 74% (203 of 276) of men and 79% (180 of 229) of women ( P = .19). Cervical arterial imaging occurred in 91% (208 of 229) of women and 86% (237 of 276) of men ( P = .09). Intracranial vascular imaging was performed in 75% (207 of 276) of men and 79% (181 of 229) of women ( P = .28). Conclusions: Our findings suggest no significant sex differences in the extent to which major diagnostic tests were performed in patients in ISGS. Dedicated tertiary stroke centers may reduce the sex bias in stroke evaluation that has been identified by previous studies.

Background There is marked variability in the reported stroke rates among persons with heart failure (HF). We performed a meta-analysis to provide summary estimates of the stroke rate in HF and to explain heterogeneity in the existing literature. We will summarize the ischemic stroke rate at various time points during follow-up among adults with chronic heart failure. Methods and Results A systematic review of the electronic literature in Medline and PubMed as well as hand searching of the reference lists of identified articles and of the meeting abstracts for the 1995–2004 American College of Cardiology and American Heart Association scientific sessions was performed to identify qualifying studies. Articles were included if they included a population with chronic HF and reported the number (or percent) of persons with HF who experienced an ischemic stroke during follow-up. Studies were excluded if the study population included ≥50% of persons with acute (postmyocardial infarction) HF, or if ≥50% of the study population required artificial support with a ventricular assist device or parenteral inotropic medications. Case reports, case series, and nonoriginal research articles were not included. Determination of study eligibility and data extraction were conducted by 2 independent reviewers using standardized forms. Results are reported as stroke rate per 1000 cases of HF, with 95% Poisson confidence intervals. Pooled estimates of the stroke rate were calculated with fixed and random effects models. Heterogeneity was explored according to a priori specified subgroup analyses. Overall, 26 studies met inclusion criteria. Eighteen of every 1000 persons suffered a stroke during the first year after the diagnosis of HF. The stroke rate increased to a maximum of 47.4 per 1000 at 5 years. Studies with fewer women, those conducted in 1990 or earlier, and cohort studies reported higher stroke rates than studies with more women, those conducted after 1990, and clinical trials. Conclusions Stroke is an important complication among persons with HF. Variability among reported stroke rates can be explained in part by differences in study design, patient population, and HF standards of care at the time of the study. Despite the heterogeneity in reported stroke rates, this meta-analysis shows that stroke prevention in HF represents an opportunity to prevent morbidity and save many lives in this highly fatal disease.

Genetic variants in the gene encoding integrin α2 ( ITGA2) have been reported to be associated with an increased risk for ischemic stroke. The purpose of this study was to investigate the association between haplotype-tagging single-nucleotide polymorphisms (tSNPs) in ITGA2 and risk of ischemic stroke in a collection of North American stroke cases and controls. The study included 484 cases and 263 controls. Thirteen tSNPs were genotyped. Association tests at and across each tSNP were performed, including haplotype association analysis. Secondary analyses considered stroke subtypes on the basis of Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. We observed significant association between tSNP rs3756541 (additive model, odds ratio (OR), 1.49; 95% confidence interval (CI), 1.11 to 2.04; P = 0.009) and disease and a trend toward association at rs2303124 (recessive model, OR, 1.56; 95% CI, 1.05 to 2.33; P = 0.03). These associations remained significant in the haplotype analyses. The associated tSNPs did not distinguish stroke etiology after application of TOAST criteria. Our results suggest that genetic variability within ITGA2 may confer risk for ischemic stroke independent of conventional risk factors. These results provide additional support for a role for platelet receptor genes in the pathogenesis of ischemic stroke of diverse subtypes.

Background Cardiac surgery is associated with cerebral dysfunction. While 1% to 2% of patients experience stroke, cognitive deficits are seen in more than half of patients. Given the high incidence of cognitive decline, it has become the endpoint of many cardiac surgery investigations. Because the elderly are at highest risk, this investigation sought to determine if there is a relationship between new ischemic changes demonstrated by diffusion-weighted magnetic resonance imaging (DW-MRI) and postoperative cognitive deficit in older patients. Methods Fifty cardiac surgical patients (>65 years of age) underwent preoperative and postoperative neurocognitive examinations, including four to six week, postdischarge, follow-up. This evaluation assessed higher cortical function, memory, attention, concentration, and psychomotor performance. Objective evidence of acute cerebral ischemic events was identified using DW-MRI. Scans were analyzed by a neuroradiologist blinded to clinical status and cognitive outcomes. Results Among patients with a mean age of 73 years, 88% demonstrated cognitive decline in the postoperative testing period while 32% showed evidence of acute perioperative cerebral ischemia by DW-MRI. At postdischarge follow-up, 30% of patients showed cognitive impairment. However, cognitive decline assessed postoperatively, or at a four to six week follow-up, was unrelated to the presence or absence of DW-MRI detected cerebral ischemia. Conclusions Postoperative neurocognitive impairment, assessed by standard means, is unrelated to acute cerebral ischemia detected by DW-MRI. This strongly suggests that cognitive decline after cardiac surgery is a function of underlying patient factors rather than perioperative ischemic events. This observation has broad implications for future investigation of strategies to prevent cardiac surgery-related neurologic injury.

Objective: To establish whether subtypes of ischemic stroke aggregate within ischemic stroke–affected sibling pairs more than expected by chance alone. Methods: This retrospective family study was based on a pooled analysis of two cohorts of male and female adult sibling pairs with symptomatic ischemic stroke. One hospital-based cohort of 404 individuals (first proband seen August 30, 1999) was recruited from the United States and Canada, and another population-based cohort of 198 individuals (first proband seen April 17, 1997) was recruited from Umea, Sweden. Subtype diagnoses were based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Results: Agreement for subtype diagnoses within families was poor (mean ± asymptotic SE κ = 0.17 ± 0.04). Occurrence of one ischemic stroke subtype in a proband was not associated with a greater likelihood of that subtype being the qualifying stroke subtype in the sibling. Comparable levels of agreement were seen when restricting the analysis to same-sex sibling pairs (κ = 0.22 ± 0.05) to sibling pairs in which the proband’s stroke occurred before the age of 65 years (κ = 0.16 ± 0.05) or to pairs in which the proband’s stroke occurred at or after the age of 65 years (κ = 0.19 ± 0.05). Conclusions: The subtype of ischemic stroke in a proband was a poor determinant of the subtype of ischemic stroke in the respective sibling. This suggests that many genetic risk factors for ischemic stroke may not be specific for one subtype.

Purpose: The safety of revascularization for asymptomatic carotid stenosis, and the efficacy of medical therapy for stroke prevention have improved. Therefore, results of prior randomized trials may not apply to current treatment decisions. The NINDS-funded CREST-2 will compare carotid endarterectomy and intensive medical therapy (IMT) versus IMT alone (n=1240), and carotid stenting and IMT versus IMT alone (n=1240) in asymptomatic patients with≥70% stenosis. Materials & Methods: CREST-2 consists of two parallel randomized clinical trials to be conducted at a target of ≈120 centers, including within NINDS StrokeNet. The composite primary outcome is stroke or death during the peri-procedural period or ipsilateral ischemic stroke thereafter up to 4 years. Blinded assessment of cognition will be done periodically. Centrally directed IMT includes tight control of blood pressure (systolic target Results: As of June 12, 2015, 94 centers have been approved by the Site Selection Committee. Credentialing is ongoing, with 198 approved surgeons and 64 approved interventionists; 124 additional conditionally approved interventionists will be able to submit additional cases for review under the CREST-2 Registry. The Centers for Medicare and Medicaid will offer CAS reimbursement for Registry enrollees. As of June 12, 2015, there are 39 actively enrolling centers, and 37 patients have been randomized. Conclusion: CREST-2 is designed to identify the best approach for asymptomatic carotid stenosis. The first patient was randomized in December, 2014. An update will be provided regarding the numbers of patients randomized, centers certified, as well as surgeons and interventionists fully approved. Registration: ClinicalTrials.gov Identifier: NCT02089217

Introduction: The risk of stroke or transient ischemic attack (TIA) remains increased after transcatheter aortic valve replacement (TAVR), especially in the first 30 days. Limited data is available regarding the impact of procedural characteristics on risk of stroke/TIA. Hypothesis: Post deployment balloon dilatation (PD) and total number of balloon dilatations (pre, valve and post insertion) may be associated with increased risk of stroke/TIA in patients undergoing TAVR. Methods: We included consecutive patients who underwent balloon-expandable TAVR until June 2014 at Mayo Clinic, Rochester. Patients who died in the operating room, converted to open surgery, or had valve-in-valve, or underwent self-expanding TAVR were excluded. Primary end-point was stroke or TIA at 30 days. Results: Mean age was 80.9±8 y, mean STS score was 8.3±5 and 50% underwent transfemoral access. The overall incidence of PD was 14% (n=53). Total number of dilations ranged from 2-7, with 5% (n=19) getting ≥ 4 total dilatations. Out of the 370 patients, 13 patients (3.5%) suffered stroke/TIA (9.4% in PD group vs. 2.2% in non-PD group) in the first 30 days after TAVR. Cox-proportional hazards regression analysis indicated that PD during TAVR was associated with a significantly increased risk of 30-day stroke/TIA (HR, 3.8; 95% CI, 1.2-11.6; p=0.02). There was a trend towards increased stroke/TIA with total number of dilations (HR, 1.5; 95% CI, 0.87-2.6; p=0.14), longer procedural time (HR per 30 minutes, 1.3; 95% CI, 0.96-1.7; p=0.09) and severity of atherosclerosis (moderate-severe - HR, 1.9; 95% CI 0.95- 3.8; p=0.07). PD was not significantly associated with the risk of 30 day death (HR, 1.1; 95% CI, 0.24-4.85; p=0.93). Conclusions: In patients undergoing PD after balloon-expandable TAVR, 9.4% suffered a stroke or TIA in the first 30 days. PD was associated with a four-fold increase in 30 day risk of stroke or TIA.

The clinical significance of cerebral microbleeds (CMB) in patients hospitalized with atrial fibrillation (AF) and cerebral ischemia is unclear. We aimed to determine the prevalence of CMB in this population and determine the future risk of intracerebral hemorrhage (ICH) and cerebral infarction (CI). The medical records and brain imaging of patients hospitalized with cerebral ischemia due to AF between 2008 and 2011 were reviewed. Followup was obtained through medical record review, mailed survey, and acquisition of death certificates. Prevalence was calculated from those patients with a hemosiderin-sensitive MRI sequence. Recurrent CI and ICH were calculated using Kaplan-Meier curves censored at 3 years. Among 426 patients hospitalized with cerebral ischemia due to AF, 134 had an MRI with hemosiderin-sensitive sequences. The prevalence of CMB was 27.6%. At 3 years, 90.6% of CMB-negative patients were overall stroke free (ICH and CI) compared to 78.6% CMB-positive patients (p = 0.0591). Only one patient in the CMB-positive group had an ICH distant to the CMB. There was a nonsignificant trend toward higher recurrent CI, recurrent overall stroke rate, and mortality in patients with 5 or more CMB compared to 0-4 CMB. The rate of prospective CI in patients with prior cerebral ischemia due to AF is higher than the rate of ICH in patients with CMB. Further study is warranted to assess larger numbers of patients to determine appropriate antithrombotic use in this high-risk population.