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Context The relative advantages and disadvantages of checklists and global rating scales ( GRS s) have long been debated. To compare the merits of these scale types, we conducted a systematic review of the validity evidence for checklists and GRS s in the context of simulation‐based assessment of health professionals. Methods We conducted a systematic review of multiple databases including MEDLINE , EMBASE and S copus to F ebruary 2013. We selected studies that used both a GRS and checklist in the simulation‐based assessment of health professionals. Reviewers working in duplicate evaluated five domains of validity evidence, including correlation between scales and reliability. We collected information about raters, instrument characteristics, assessment context, and task. We pooled reliability and correlation coefficients using random‐effects meta‐analysis. Results We found 45 studies that used a checklist and GRS in simulation‐based assessment. All studies included physicians or physicians in training; one study also included nurse anaesthetists. Topics of assessment included open and laparoscopic surgery ( n = 22), endoscopy ( n = 8), resuscitation ( n = 7) and anaesthesiology ( n = 4). The pooled GRS –checklist correlation was 0.76 (95% confidence interval [ CI ] 0.69–0.81, n = 16 studies). Inter‐rater reliability was similar between scales ( GRS 0.78, 95% CI 0.71–0.83, n = 23; checklist 0.81, 95% CI 0.75–0.85, n = 21), whereas GRS inter‐item reliabilities (0.92, 95% CI 0.84–0.95, n = 6) and inter‐station reliabilities (0.80, 95% CI 0.73–0.85, n = 10) were higher than those for checklists (0.66, 95% CI 0–0.84, n = 4 and 0.69, 95% CI 0.56–0.77, n = 10, respectively). Content evidence for GRS s usually referenced previously reported instruments ( n = 33), whereas content evidence for checklists usually described expert consensus ( n = 26). Checklists and GRS s usually had similar evidence for relations to other variables. Conclusions Checklist inter‐rater reliability and trainee discrimination were more favourable than suggested in earlier work, but each task requires a separate checklist. Compared with the checklist, the GRS has higher average inter‐item and inter‐station reliability, can be used across multiple tasks, and may better capture nuanced elements of expertise.

Objective Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome‐wide association analysis of Takayasu arteritis. Methods Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1‐Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis. Results We identified genetic susceptibility loci for Takayasu arteritis with a genome‐wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10 −9 ), RPS9 / LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10 −8 ), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10 −10 ). The genetic susceptibility locus in RPS9 / LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin‐like receptor gene LILRB3 ( P = 2.29 × 10 −8 ). In addition, we identified candidate susceptibility genes with suggestive levels of association ( P < 1 × 10 −5 ) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1 , and PTK2B . Conclusion Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.

Background In epidemiologic studies, obesity has been associated with reduced natriuretic peptide ( NP ) concentrations. Reduced NP production could impair the ability of obese individuals to respond to salt loads, increasing the risk of hypertension and other disorders. We hypothesized that weight loss enhances NP production before and after salt loading. Methods and Results We enrolled 15 obese individuals (mean BMI 45±5.4 kg/m 2 ) undergoing gastric bypass surgery. Before and 6 months after surgery, subjects were admitted to the clinical research center and administered a large‐volume intravenous saline challenge. Echocardiography and serial blood sampling were performed. From the pre‐operative visit to 6 months after surgery, subjects had a mean BMI decrease of 27%. At the 6‐month visit, N‐terminal pro‐atrial NP (Nt‐pro ANP ) levels were 40% higher before, during, and after the saline infusion, compared with levels measured at the same time points during the pre‐operative visit ( P <0.001). The rise in Nt‐pro‐ ANP induced by the saline infusion (≈50%) was similar both before and after surgery (saline, P <0.001; interaction, P =0.2). Similar results were obtained for BNP and Nt‐pro BNP ; resting concentrations increased by 50% and 31%, respectively, after gastric bypass surgery. The increase in NP concentrations after surgery was accompanied by significant decreases in mean arterial pressure ( P =0.004) and heart rate ( P <0.001), and an increase in mitral annular diastolic velocity ( P =0.02). Conclusion In obese individuals, weight loss is associated with a substantial increase in the “setpoint” of circulating NP concentrations. Higher NP concentrations could contribute to an enhanced ability to handle salt loads after weight loss.

Background and Purpose— The relationships between cerebrovascular lesions visible on imaging and cognition are complex. We explored the possibility that the cerebral cortical volume mediated these relationships. Methods— Total of 1906 nondemented participants (59% women; 25% African–American; mean age, 76.6 years) in the Atherosclerosis Risk in Communities (ARIC) study underwent cognitive assessments, risk factor assessments, and quantitative MRI for white matter hyperintensities (WMH) and infarcts. The Freesurfer imaging analysis pipeline was used to determine regional cerebral volumes. We examined the associations of cognitive domain outcomes with cerebral volumes (hippocampus and separate groups of posterior and frontal cortical regions of interest) and cerebrovascular imaging features (presence of large or small cortical/subcortical infarcts and WMH volume). We performed mediation pathway analyses to assess the hypothesis that hippocampal and cortical volumes mediated the associations between cerebrovascular imaging features and cognition. Results— In unmediated analyses, WMH and infarcts were both associated with worse psychomotor speed/executive function. In mediation analyses, WMH and infarct associations on psychomotor speed/executive function were significantly attenuated, but not abolished, by the inclusion of the posterior cortical regions of interest volume in the models, and the infarcts on psychomotor speed/executive function association were attenuated, but not abolished, by inclusion of the frontal cortical regions of interest volume. Conclusions— Both WMH and infarcts were associated with cortical volume, and both lesions were also associated with cognitive performance, implying shared pathophysiological mechanisms. Although cross-sectional, our findings suggest that WMH and infarcts could be proxies for clinically covert processes that directly damage cortical regions. Microinfarcts are 1 candidate for such a clinically covert process.

OBJECT Precise localization and understanding of the origin of spontaneous high-flow spinal CSF leaks is required prior to targeted treatment. This study demonstrates the utility of ultrafast dynamic CT myelography for the precise localization of high-flow CSF leaks caused by spiculated spinal osteophytes. METHODS This study reports a series of 14 patients with high-flow CSF leaks caused by spiculated spinal osteophytes who underwent ultrafast dynamic CT myelography between March 2009 and December 2010. There were 10 male and 4 female patients, with an average age of 49 years (range 37–74 years). The value of ultrafast dynamic CT myelography in depicting the CSF leak site was qualitatively assessed. RESULTS In all 14 patients, ultrafast dynamic CT myelography was technically successful at precisely demonstrating the site of the CSF leak, the causative spiculated osteophyte piercing the dura, and the relationship of the implicated osteophyte to adjacent structures. Leak sites included 3 cervical, 11 thoracic, and 0 lumbar levels, with 86% of the leaks occurring from C-5 to T-7. Information obtained from the ultrafast dynamic CT myelogram was considered useful in all treated CSF leaks. CONCLUSIONS Spinal osteophytes piercing the dura are a more frequent cause of high-flow CSF leaks than previously recognized. Ultrafast dynamic CT myelography adds value beyond standard dynamic myelography or digital subtraction myelography in the diagnosis and anatomical characterization of high-flow spinal CSF leaks caused by these osteophytes. This information allows for appropriate planning for percutaneous or surgical treatment.

AbstractBackgroundLate‐onset Alzheimer's disease (AD) is heritable with 20 genes showing genome‐wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis.MethodsThe ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.ResultsALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10−12 after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10−11), cholesterol transport (P = 2.96 × 10−9), and proteasome‐ubiquitin activity (P = 1.34 × 10−6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002–.05).ConclusionsThe immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.

Significance Long noncoding RNAs (lncRNAs) are involved in numerous biological roles including epigenetic regulation, apoptosis, and cell cycle. Whereas lncRNAs contribute to epigenetic gene regulation, metastasis, and prognosis in solid tumors, their role in acute myeloid leukemia (AML) has not been hitherto reported. Here, we show that lncRNA expression profiles are associated with recurrent mutations, clinical features, and outcome in AML. A fraction of these lncRNAs may have a functional role in leukemogenesis. Furthermore, lncRNAs could be used as biomarkers for outcome in AML. The identification of patients likely to achieve complete remission with standard therapy alone, based on lncRNA expression, is a significant advance potentially sparing such patients from other toxicities and focusing investigational approaches on postremission studies.