Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

Introduction: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. Methods: For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland–Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. Results: The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Conclusion: Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs

Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis

Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10−10). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression rg = 0.63, insomnia rg = 0.47), physical health (overweight rg = 0.19, waist-to-hip ratio rg = 0.32), smoking (rg = 0.54), cognitive ability (intelligence rg = −0.40), educational attainment (years of schooling rg = −0.46) and reproductive traits (age at first birth rg = −0.58, father’s age at death rg = −0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB

Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN): Design and statistical analysis plan of the extended follow-up study

Background: MR CLEAN was the first randomized trial to demonstrate the short-term clinical effectiveness of endovascular treatment in patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation. Several other trials confirmed that endovascular treatment improves clinical outcome at three months. However, limited data are available on long-term clinical outcome. We aimed to estimate the effect of endovascular treatment on functional outcome at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed to assess the effect of endovascular treatment on major vascular events and mortality during two years of follow-up. Methods: MR CLEAN is a multicenter clinical trial with randomized treatment allocation, open-label treatment, and blinded endpoint evaluation. Patients included were 18 years or older with acute ischemic stroke caused by a proven anterior proximal artery occlusion who could be treated within six hours after stroke onset. The intervention contrast was endovascular treatment and usual care versus no endovascular treatment and usual care. The current study extended the follow-up duration from three months to two years. The primary outcome is the score on the modified Rankin scale at two years. Secondary outcomes include all-cause mortality and the occurrence of major vascular events within two years of follow-up. Discussion: The results of our study provide information on the long-term clinical effectiveness of endovascular treatment, which may have implications for individual treatment decisions and estimates of cost-effectiveness. Trial registration:NTR1804. Registered on 7 May 2009; ISRCTN10888758. Registered on 24 July 2012 (main MR CLEAN trial); NTR5073. Registered on 26 February 2015 (extended follow-up study)

Emergence of surfactant-​free micelles from ternary solutions

Curious effects ranging from enzyme activity to anomalies in evapn. rates that have been known for over fifty years suggest the existence and thermodn. stability of surfactant-free micelles. Only recently, joint X-ray, light and neutron scattering expts. have demonstrated that aggregates and bulk pseudo-phases coexist in presumably normal solns., in which a water insol. component is solubilized in a certain domain of concn. of a hydrotrope component like ethanol. Nevertheless, nothing is known about the mol.-level shape and structure of such aggregates. In this work we characterize mixts. of octanol, ethanol, and water by mol. dynamics simulations. For compns. in the "pre-ouzo" region (close to the single phase stability limit) we observe micelle-like aggregates that are clearly distinct from simple crit. d. fluctuations. We define an ethanol partition in the pseudo-phase from an integral of the van der Waals dispersion energy term. From this partition, octanol-rich aggregates swollen with ethanol appear with an emerging interface. Ethanol is present in the water pseudo-phase with an exponential decay similar to the one predicted by Marcelja and Radic forty years ago

Grading of Crohn's disease activity using CT, MRI, US and scintigraphy: a meta-analysis

To assess the grading of Crohn's disease activity using CT, MRI, US and scintigraphy. MEDLINE, EMBASE and Cochrane databases were searched (January 1983-March 2014) for studies evaluating CT, MRI, US and scintigraphy in grading Crohn's disease activity compared to endoscopy, biopsies or intraoperative findings. Two independent reviewers assessed the data. Three-by-three tables (none, mild, frank disease) were constructed for all studies, and estimates of accurate, over- and under-grading were calculated/summarized by fixed or random effects models. Our search yielded 9356 articles, 19 of which were included. Per-patient data showed accurate grading values for CT, MRI, US and scintigraphy of 86% (95% CI: 75-93%), 84% (95% CI: 67-93%), 44% (95% CI: 28-61%) and 40% (95% CI: 16-70%), respectively. In the per-patient analysis, CT and MRI showed similar accurate grading estimates (P = 0.8). Per-segment data showed accurate grading values for CT and scintigraphy of 87% (95% CI: 77-93%) and 86% (95% CI: 80-91%), respectively. MRI and US showed grading accuracies of 67-82% and 56-75%, respectively. CT and MRI showed comparable high accurate grading estimates in the per-patient analysis. Results for US and scintigraphy were inconsistent, and limited data were available. • CT and MRI have comparable high accuracy in grading Crohn's disease. • Data on US and scintigraphy is inconsistent and limited. • MRI is preferable over CT as it lacks ionizing radiation exposur

Effect of balloon angioplasty in femoropopliteal arteries assessed by intravascular ultrasound

OBJECTIVE: To study the effects of balloon angioplasty (PTA) of the femoropopliteal artery with intravascular ultrasound (IVUS). MATERIALS AND METHODS: Corresponding IVUS cross-sections (n = 1033) obtained before and after PTA from 115 procedures were analysed. Vascular damage including plaque rupture, dissection and media rupture was assessed. Free lumen area (FLA), media-bounded area (MBA) and plaque area (PLA) were measured. RESULTS: After PTA vascular damage was seen at the target site in 83 (72%) arteries: plaque rupture in 30 (26%), dissection in 66 (57%) and media rupture in 20 (17%) arteries. The FLA increased from 5.4 +/- 3.4 mm2 to 14.1 +/- 5.0 mm2 (p or = 6 mm. CONCLUSIONS: Vascular damage is common following PTA. Lumen gain is mainly due to vessel expansion and, to a lesser extent, to a decrease in plaque are

Long-Term Performance of Readers Trained in Grading Crohn Disease Activity Using MRI

We aim to evaluate the long-term performance of readers who had participated in previous magnetic resonance imaging (MRI) reader training in grading Crohn disease activity. Fourteen readers (8 women; 12 radiologists, 2 residents; mean age 40; range 31-59), who had participated in a previous MRI reader training, participated in a follow-up evaluation after a mean interval of 29 months (range 25-34 months). Follow-up evaluation comprised 25 MRI cases of suspected or known Crohn disease patients with direct feedback; cases were identical to the evaluation set used in the initial reader training (of which readers were unaware). Grading accuracy, overstaging, and understaging were compared between training and follow-up using a consensus score by two experienced abdominal radiologists as the reference standard. In the follow-up evaluation, overall grading accuracy was 73% (95% confidence interval [CI]: 62%-81%), which was comparable to reader training grading accuracy (72%, 95% CI: 61%-80%) (P = .66). Overstaging decreased significantly from 19% (95% CI: 12%-27%) to 13% (95% CI: 8%-21%) between training and follow-up (P = .03), whereas understaging increased significantly from 9% (95% CI: 4%-21%) to 14% (95% CI: 7%-26%) (P  < .01). Readers have consistent long-term accuracy for grading Crohn disease activity after case-based reader training with direct feedbac