Cohort profile of the UK Biobank: diagnosis and characteristics of cerebrovascular disease

Purpose: The UK Biobank is a large-scale biomedical resource, containing sociodemographic and medical information, including data on a previous diagnosis of stroke or transient ischaemic attack (TIA). We described these participants and their medication usage. Participants: We identified participants who either self-reported or were identified from a nurse-led interview, having suffered a stroke or a TIA and compared them against participants without stroke ort TIA. We assessed their risk factor burden (sex, age, deprivation, waist to hip ratio (WHR), hypertension, smoking, alcohol intake, diabetes, physical exercise and oral contraception use (oral contraceptive pill, OCP)) and medication usage. Findings: to date We studied 502 650 people (54.41% women), 6669 (1.23%) participants self-reported a stroke. The nurse-led interview identified 7669 (1.53%) people with stroke and 1781 (0.35%) with TIA. Hypertension, smoking, higher WHR, lower alcohol consumption and diabetes were all more common in people with cerebrovascular disease (p<0.0001 for each). Women with cerebrovascular disease were less likely to have taken the OCP (p=0.0002). People with cerebrovascular disease did more exercise (p=0.03). Antithrombotic medication was taken by 81% of people with stroke (both self-report and nurse-led responders) and 89% with TIA. For self-reported stroke, 63% were taking antithrombotic and cholesterol medications, 54% taking antithrombotic and antihypertensive medications and 46% taking all 3. For the nurse-led interview and TIA, these figures were 65%, 54% and 46%, and 70%, 53% and 45%, respectively. Future plans: The UK Biobank provides a large, generalisable and contemporary data source in a young population. The characterisation of the UK Biobank cohort with cerebrovascular disease will form the basis for ongoing research using this data source

Reliability of the modified Rankin Scale: a systematic review

<p><b>Background and Purpose:</b> A perceived weakness of the modified Rankin Scale is potential for interobserver variability. We undertook a systematic review of modified Rankin Scale reliability studies.</p> <p><b>Methods:</b> Two researchers independently reviewed the literature. Crossdisciplinary electronic databases were interrogated using the following key words: Stroke*; Cerebrovasc*; Modified Rankin*; Rankin Scale*; Oxford Handicap*; Observer variation*. Data were extracted according to prespecified criteria with decisions on inclusion by consensus.</p> <p><b>Results:</b> From 3461 titles, 10 studies (587 patients) were included. Reliability of modified Rankin Scale varied from weighted κ=0.95 to κ=0.25. Overall reliability of mRS was κ=0.46; weighted κ=0.90 (traditional modified Rankin Scale) and κ=0.62; weighted κ=0.87 (structured interview).</p> <p><b>Conclusion:</b> There remains uncertainty regarding modified Rankin Scale reliability. Interobserver studies closest in design to large-scale clinical trials demonstrate potentially significant interobserver variability.</p&gt

Exploring the reliability of the modified Rankin Scale

<p><b>Background and Purpose:</b> The modified Rankin Scale (mRS) is the most prevalent outcome measure in stroke trials. Use of the mRS may be hampered by variability in grading. Previous estimates of the properties of the mRS have used diverse methodologies and may not apply to contemporary trial populations. We used a mock clinical trial design to explore inter- and intraobserver variability of the mRS.</p> <p><b>Methods:</b> Consenting patients with stroke attending for outpatient review had the mRS performed by 2 independent assessors with pairs of assessors selected from a team of 3 research nurses and 4 stroke physicians. Before formal assessment, interviewers estimated disability based only on initial patient observation. Each patient was then randomized to undergo the mRS using standard assessment or a prespecified structured interview. The second interviewer in the pair reassessed the patient using the same method blinded to the colleague’s score. For each patient assessed, one rater was randomly assigned to video record their interview. After 3 months, this interviewer reviewed and regraded their original video assessment.</p> <p><b>Results:</b> Across 100 paired assessments, interobserver agreement was moderate (k=0.57). Intraobserver variability was good (k=0.72) but less than would be expected from previous literature. Forty-nine assessments were performed using the structured interview approach with no significant difference between structured and standard mRS. Researchers were unable to reliably predict mRS from initial limited patient assessment (k=0.16).</p> <p><b>Conclusions:</b> Despite availability of training and structured interview, there remains substantial interobserver variability in mRS grades awarded even by experienced researchers. Additional methods to improve mRS reliability are required.</p&gt

Variability in modified rankin scoring across a large cohort of observers

<br>Background and Purpose— The modified Rankin scale (mRS) is the most commonly used outcome measure in stroke trials. However, substantial interobserver variability in mRS scoring has been reported. These studies likely underestimate the variability present in multicenter clinical trials, because exploratory work has only been undertaken in single centers by a few observers, all of similar training. We examined mRS variability across a large cohort of international observers using data from a video training resource.</br> <br>Methods— The mRS training package includes a series of “real-life” patient interviews for grading. Training data were collected centrally and analyzed for variability using kappa statistics. We examined variability against a standard of “correct” mRS grades; examined variability by country; and for UK assessors, examined variability by center and by professional background of the observer.</br> <br>Results— To date, 2942 assessments from 30 countries have been submitted. Overall reliability for mRS grading has been moderate to good with substantial heterogeneity across countries. Native English language has had little effect on reliability. Within the United Kingdom, there was no significant variation by profession.</br> <br>Conclusion— Our results confirm interobserver variability in mRS assessment. The heterogeneity across countries is intriguing because it appears not to be related solely to language. These data highlight the need for novel strategies to improve reliability.</br&gt

The AF structure of non commutative toroidal Z/4Z orbifolds

For any irrational theta and rational number p/q such that q|qtheta-p|<1, a projection e of trace q|qtheta-p| is constructed in the the irrational rotation algebra A_theta that is invariant under the Fourier transform. (The latter is the order four automorphism U mapped to V, V mapped to U^{-1}, where U, V are the canonical unitaries generating A_theta.) Further, the projection e is approximately central, the cut down algebra eA_theta e contains a Fourier invariant q x q matrix algebra whose unit is e, and the cut downs eUe, eVe are approximately inside the matrix algebra. (In particular, there are Fourier invariant projections of trace k|qtheta-p| for k=1,...,q.) It is also shown that for all theta the crossed product A_theta rtimes Z_4 satisfies the Universal Coefficient Theorem. (Z_4 := Z/4Z.) As a consequence, using the Classification Theorem of G. Elliott and G. Gong for AH-algebras, a theorem of M. Rieffel, and by recent results of H. Lin, we show that A_theta rtimes Z_4 is an AF-algebra for all irrational theta in a dense G_delta.Comment: 35 page

Solidification in soft-core fluids: disordered solids from fast solidification fronts

Using dynamical density functional theory we calculate the speed of solidification fronts advancing into a quenched two-dimensional model fluid of soft-core particles. We find that solidification fronts can advance via two different mechanisms, depending on the depth of the quench. For shallow quenches, the front propagation is via a nonlinear mechanism. For deep quenches, front propagation is governed by a linear mechanism and in this regime we are able to determine the front speed via a marginal stability analysis. We find that the density modulations generated behind the advancing front have a characteristic scale that differs from the wavelength of the density modulation in thermodynamic equilibrium, i.e., the spacing between the crystal planes in an equilibrium crystal. This leads to the subsequent development of disorder in the solids that are formed. For the one-component fluid, the particles are able to rearrange to form a well-ordered crystal, with few defects. However, solidification fronts in a binary mixture exhibiting crystalline phases with square and hexagonal ordering generate solids that are unable to rearrange after the passage of the solidification front and a significant amount of disorder remains in the system.Comment: 18 pages, 14 fig