Asymptotic expansions for the Laplace approximations for Itô functionals of Brownian rough paths

AbstractIn this paper, we establish asymptotic expansions for the Laplace approximations for Itô functionals of Brownian rough paths under the condition that the phase function has finitely many non-degenerate minima. Our main tool is the Banach space-valued rough path theory of T. Lyons. We use a large deviation principle and the stochastic Taylor expansion with respect to the topology of the space of geometric rough paths. This is a continuation of a series of papers by Inahama [Y. Inahama, Laplace's method for the laws of heat processes on loop spaces, J. Funct. Anal. 232 (2006) 148–194] and by Inahama and Kawabi [Y. Inahama, H. Kawabi, Large deviations for heat kernel measures on loop spaces via rough paths, J. London Math. Soc. 73 (3) (2006) 797–816], [Y. Inahama, H. Kawabi, On asymptotics of certain Banach space-valued Itô functionals of Brownian rough paths, in: Proceedings of the Abel Symposium 2005, Stochastic Analysis and Applications, A Symposium in Honor of Kiyosi Itô, Springer, Berlin, in press. Available at: http://www.abelprisen.no/no/abelprisen/deltagere_2005.html]

Validity of an enhanced EQ-5D-5L measure with an added cognitive dimension in patients with stroke

Objective: The 5-level EuroQoL (EQ-5D-5L) is a patient-reported outcome measure frequently used in stroke research. However, it does not assess the cognitive problems many patients with stroke experience. The aim of this article is to compare the content validity, internal consistency and discriminative ability of the EQ-5D-5L with and without an additional cognitive domain (EQ-5D-5L+C), administered three months post-stroke. Design: Cross-sectional study. Setting: Six general hospitals in the Netherlands. Subjects: In all, 360 individuals with stroke three months after the event. Interventions: Not applicable. Main measures: The modified Rankin Scale and EQ-5D-5L+C were administered in telephone interviews three months post-stroke. Results: A total of 360 patients with stroke were included. Mean age was 68.8 years (standard deviation (SD) = 11.7), 143 (40%) were female, 334 (93%) had had an ischemic stroke, 165 (46%) had a National Institutes of Health Stroke Scale (NIHSS) score ⩽ 4 at presentation and the Barthel Index was 17.2 (SD = 4) four days post-stroke. Cognitive problems were reported by 199 (55%) patients three months post-stroke. Internal consistencies of the EQ-5D-5L and EQ-5D-5L+C were 0.75 and 0.77, respectively. Adding a cognitive domain resulted in a decrease of the ceiling effect from 22% to 14%. Both EQ-5D-5L and EQ-5D-5L+C showed good discriminative ability, but differences between patients with different modified Rankin Scale scores and with/without reported decrease in health and daily activities were slightly larger with the EQ-5D-5L+C compared to the EQ-5D-5L. Conclusions: The EQ-5D-5L+C, which includes a cognitive domain that is highly significant for stroke patients, showed increased content validity and good discriminative ability, without losing internal consistency

В. Липинський про бюрократію ("Листи до братів-хліборобів"): до проблеми визначення теоретичного підґрунтя поглядів

Розглянуто формування поглядів В. Липинського на бюрократію під впливом ідей Ж. Сореля, Р. Міхельса, К. Маркса, А. де Токвіля. Стверджено, що основу його поглядів становлять ідеї про бюрократію, запозичені у Ж. Сореля та Р. Міхельса. Підкреслено, що під час розгляду проблеми бюрократії вітчизняний мислитель не звертався до ідей М. Вебера.Deals with the formation of attitudes of Viacheslav Lypynsky on bureaucracy under the influence of Georges Sorel, Robert Michels, Karl Marx, Alexis de Tocqueville. It is alleged that his views were based on ideas of the bureaucracy borrowed from Georges Sorel and Robert Michels. Emphasizing that, in considering the problem of bureaucracy Ukrainian thinker did not approach the ideas of Max Weber

Artistic occupations are associated with a reduced risk of Parkinson’s disease

Parkinson’s disease (PD) is preceded by a premotor phase of unknown duration. Dopaminergic degeneration during this phase may lead to subtle cognitive and behavioural changes, such as decreased novelty seeking. Consequently, premotor subjects might be most comfortable in jobs that do not require optimal dopamine levels, leading to an overrepresentation in structured and predictable occupations, or an underrepresentation in artistic occupations. In a case–control study, 750 men with PD (onset ≥40 years) and 1300 healthy men completed a validated questionnaire about their lifetime occupational status. Occupations were classified using the RIASEC model. Odds ratios (ORs) were calculated for the conventional and artistic categories, both for the most recent occupation before symptom onset, and for the very first occupation. Because farming has been associated with a PD risk, ORs were calculated separately for farming. A reduced risk of PD was found for men with an artistic occupation late in life (OR 0.14, 95 % CI 0.04–0.53), while an artistic first occupation did not prevent PD (OR 0.72, CI 0.32–1.59). Conventional occupations showed no increased risk (recent: OR 1.07, CI 0.70–1.64; first: OR 1.14, CI 0.77–1.71). In support of previous reports, farming was associated with an increased risk of PD (recent: OR 2.6, CI 1.4–4.6; first: OR 2.7, CI 1.6–4.5). PD patients were older than controls, but various statistical corrections for age all lead to similar results. Artistic occupations late in life are associated with a reduced risk of subsequent PD, perhaps because this reflects a better preserved dopaminergic state. No initial occupation predicted PD, suggesting that the premotor phase starts later in life

Are white matter lesions directly associated with cognitive impairment in patients with lacunar infarcts?

Forty-four patients (mean age 66, SD 8 years) with either clinical evidence of a focal lacunar syndrome (n = 36) or with disorders of memory or gait (n = 8) in the presence of a lacunar infarct on CT were studied for cognitive functioning and for the presence of white matter lesions on MRI. MR images were assessed by a neurologist and a neuroradiologist blinded to the clinical data. Thirty-six patients had one or more lacunar infarcts on CT or MRI (in the thalamus in 5, in the caudate nucleus in 3 and in the internal capsule or corona radiata in the remaining patients). Twelve patients had multiple infarcts. Severe lesions of the white matted were found in 13 patients, mild to moderate lesions in 20 patients. Scores on Digit Span, Digit Symbol and delayed recall of the 15-Words test were significantly lower in the group with severe lesions, whilst there was a trend in the same direction for the Cognitive part of the Cambridge Examination of Mental Disorders in the Elderly, the Trailmaking B, Stroop colour interference test and the delayed visual reproduction of the Wechsler Memory Scale. These findings suggest that diffuse lesions of the white matter are an independent factor in the pathogenesis of intellectual dysfunction, also in patients with lacunar infarcts, but a truly independent analysis is difficult because the most severe involvement of the white matter tended to be associated with the largest number of lacunar infarcts

Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke

Objective: To study the early time course of major bleeding and its subtypes in patients with cerebral ischemia on dual and single antiplatelet therapy. Methods: We performed a post hoc analysis on individual patient data from 6 randomized clinical trials (Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events [CAPRIE], Second European Stroke Prevention Study [ESPS-2], Management of Atherothrombosis With Clopidogrel in High Risk Patients [MATCH], Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA], European/Australasian Stroke Prevention in Reversible Ischaemia Trial [ESPRIT], and Prevention Regimen for Effectively Avoiding Second Strokes [PRoFESS]) including 45,195 patients with a TIA or noncardioembolic ischemic stroke. We studied incidence rates of bleeding per antiplatelet regimen stratified by time from randomization (≤30, 31–90, 91–180, 181–365, >365 days). We calculated incidence rates per trial and pooled estimates with random-effects meta-analysis. We performed Poisson regression to assess differences between time periods with adjustment for age and sex. Results: The incidence of major bleeding on aspirin plus clopidogrel and aspirin plus -dipyridamole was highest in the first 30 days, 5.8 and 4.9 per 100 person-years, respectively, and was significantly higher than at 31 to 90 days (rate ratio 1.98, 95% confidence interval 1.16–3.40 for aspirin plus clopidogrel; rate ratio 1.94, 95% confidence interval 1.24–3.03 for aspirin plus dipyridamole). Incidence rates on aspirin and clopidogrel monotherapy were 2.8 and 2.5 per 100 person-years, respectively, in the first 30 days, with no significant change over time. The time course was similar for gastrointestinal bleeds. There was no early excess of intracranial hemorrhage in patients on either dual or single antiplatelet therapy. Conclusion: Dual antiplatelet therapy is associated with high early risks of major and gastrointestinal bleeding that decline after the first month in trial cohorts

Risk factors for lobar and non-lobar intracerebral hemorrhage in patients with vascular disease

Introduction Lobar and non-lobar non-traumatic intracerebral hemorrhage (ICH) are presumably caused by different types of small vessel diseases. The aim of this study was to assess risk factors for ICH according to location. Methods In two large prospective studies, SMART (n = 9088) and ESPRIT (n = 2625), including patients with manifest cardiovascular, cerebrovascular or peripheral artery disease or with vascular risk factors, we investigated potential risk factors for ICH during follow-up according to lobar or non-lobar location by Cox proportional hazards analyses. Results During 65,156 patient years of follow up 19 patients had lobar ICH (incidence rate 29, 95% CI 19-42 per 100,000 person-years) and 24 non-lobar ICH (incidence rate 37, 95% CI 26-51 per 100,000 person-years). Age significantly increased the risk of lobar ICH (HR per 10 years increase 1.90; 95% CI 1.17-3.10) in the multivariable analysis, but not of non-lobar hemorrhage. Anticoagulant medication (HR 3.49; 95% CI 1.20-10.2) and male sex (HR 3.79; 95% CI 1.13-12.8) increased the risk of non-lobar but not lobar ICH. Conclusion This study shows an elevated risk of future ICH in patients with manifestations of, or risk factors for, cardiovascular, cerebrovascular or peripheral artery disease. Our data suggest that risk factors for ICH vary according to location, supporting the hypothesis of a differential pathophysiology of lobar and non-lobar ICH

Nonfocal transient neurological attacks in patients with carotid artery occlusion

Item does not contain fulltex

Automated measurement of brain and white matter lesion volume in type 2 diabetes mellitus

Aims/hypothesis: Type 2 diabetes mellitus has been associated with brain atrophy and cognitive decline, but the association with ischaemic white matter lesions is unclear. Previous neuroimaging studies have mainly used semiquantitative rating scales to measure atrophy and white matter lesions (WMLs). In this study we used an automated segmentation technique to investigate the association of type 2 diabetes, several diabetes-related risk factors and cognition with cerebral tissue and WML volumes. Subjects and methods: Magnetic resonance images of 99 patients with type 2 diabetes and 46 control participants from a population-based sample were segmented using a k-nearest neighbour classifier trained on ten manually segmented data sets. White matter, grey matter, lateral ventricles, cerebrospinal fluid not including lateral ventricles, and WML volumes were assessed. Analyses were adjusted for age, sex, level of education and intracranial volume. Results: Type 2 diabetes was associated with a smaller volume of grey matter (-21.8 ml; 95% CI -34.2, -9.4) and with larger lateral ventricle volume (7.1 ml; 95% CI 2.3, 12.0) and with larger white matter lesion volume (56.5%; 95% CI 4.0, 135.8), whereas white matter volume was not affected. In separate analyses for men and women, the effects of diabetes were only significant in women. Conclusions/interpretation: The combination of atrophy with larger WML volume indicates that type 2 diabetes is associated with mixed pathology in the brain. The observed sex differences were unexpected and need to be addressed in further studies. © 2007 Springer-Verlag

Comparison of oxygen-15 PET and transcranial Doppler CO2-reactivity measurements in identifying haemodynamic compromise in patients with symptomatic occlusion of the internal carotid artery

BACKGROUND: Transcranial Doppler (TCD) CO(2)-reactivity and oxygen-15 positron emission tomography (PET) have both been used to measure the cerebral haemodynamic state in patients who may have a compromised blood flow. Our purpose was to investigate whether PET and TCD identify the same patients with an impaired flow state of the brain in patients with internal carotid artery (ICA) occlusion. METHODS: Patients with recent transient ischaemic attack or minor ischaemic stroke associated with ICA occlusion underwent TCD with measurement of CO(2)-reactivity and oxygen-15 PET within a median time interval of 6 days. RESULTS: We included 24 patients (mean age 64 ± 10 years). Seventeen (71%) patients had impaired CO(2)-reactivity (≤20%), of whom six had absent reactivity (0%) or steal (<0%) in the hemisphere ipsilateral to the ICA occlusion. PET of the perfusion state of the hemisphere ipsilateral to the ICA occlusion demonstrated stage 1 haemodynamic compromise (decreased cerebral blood flow (CBF) or increased cerebral blood volume (CBV) without increased oxygen extraction fraction (OEF)) in 13 patients and stage 2 (increased OEF) in 2 patients. In 12 patients (50%), there was agreement between TCD and PET, indicating haemodynamic compromise in 10 and a normal flow state of the brain in 2 patients. There was no significant correlation between CO(2)-reactivity and CBF ipsilateral/contralateral hemispheric ratio (r = 0.168, p value = 0.432), OEF ratio (r = −0.242, p value = 0.255), or CBV/CBF ratio (r = −0.368, p value = 0.077). CONCLUSIONS: In patients with symptomatic ICA occlusion, identification of an impaired flow state of the brain by PET and TCD CO(2)-reactivity shows concordance in only half of the patients