Research in schizophrenia has increasingly focused on incorporating measures from cognitive neuroscience, but little is known about their psychometric characteristics. Here, we extend prior research by reporting on temporal stability, as well as age and sex effects, for cognitive neuroscience paradigms optimized as part of the Cognitive Neuroscience Test Reliability and Clinical applications for Schizophrenia consortium. Ninety-nine outpatients with schizophrenia and 131 healthy controls performed 5 tasks assessing 4 constructs at 3 sessions. The constructs were (1) Goal maintenance (Dot Probe Expectancy [DPX] and AX continuous performance tasks [AX-CPT]); (2) Episodic memory (Relational and Item-Specific Encoding and Retrieval task [RiSE]); (3) Visual integration (Jittered Orientation Visual Integration task [JOVI]); and (4) Perceptual gain control (Contrast-Contrast Effect Task [CCE]). Patients performed worse than controls on all but the CCE, and the magnitude of these group differences was stable across sessions, with no sex differences observed. Improvements over sessions were seen for the AX-CPT, the DPX, and the JOVI though practice effects for the AX-CPT and the DPX were primarily present in older participants. For the AX-CPT and the JOVI, practice effects were larger for T1 to T2 than for T2 to T3. Age was associated with poor associative recognition on the RiSE and accuracy on the JOVI. Test-rest reliability ranged from poor for the JOVI threshold score to adequate to good for the DPX, AX-CPT, and JOVI accuracy measures, with RiSE and CCE measures in the moderate range. These results suggest that group differences in DPX, AX-CPT, RiSE, and JOVI are robust and consistent across repeated testing.

BackgroundSince 2015, mechanical thrombectomy has been the standard treatment for emergent large vessel occlusion ischemic stroke.ObjectiveTo investigate, using the previously published Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (clinicaltrials.gov NCT03153683), how the protein expression of a patient’s intracranial blood during ischemic stroke compares with the protein expression of their systemic arterial blood in order to better understand and treat stroke.MethodsPlasma samples from 25 subjects underwent proteomic analysis, where intracranial protein expression was compared with systemic protein levels. Data including sex, comorbidities, infarct volume, and infarct time were included for each subject.ResultsA majority of important proteins had a lower expression in intracranial blood than in systemic arterial blood. Proteins with the most significant changes in expression were: endopeptidase at −0.26 (p<0.0001), phospholipid transfer protein (PLTP) at −0.26 (p=0.0005), uromodulin (UMOD) at −0.14 (p=0.002), ficolin-2 (FCN2) at −0.46 (p=0.005), C-C motif chemokine 19 (CCL19) at −0.51 (p<0.0001), C-C motif chemokine 20 (CCL20) at −0.40 (p<0.0001), fibroblast growth factor 21 at −0.37 (p=0.0002), and C-C motif chemokine (CCL23) at −0.43 (p=0.0003).ConclusionsEvaluation of proteomic changes in the intravascular space of a cerebral infarct in progress in human subjects suggested that changes in proteins such PLTP, fetuin-B (FETUB), and FCN2 may be involved in atherosclerotic changes, and chemokines such as CCL23 are known to play a role in the Th2 autoimmune response. These data provide a scientific springboard for identifying clinically relevant biomarkers for diagnosis/prognosis, and targets for much needed neuroprotective/neuroreparative pharmacotherapies.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Practice patterns surrounding awake extubation of pediatric surgical patients remain largely undocumented. This study assessed the value of commonly used predictors of fitness for extubation to determine which were most salient in predicting successful extubation following emergence from general anesthesia with a volatile anesthetic in young children. Methods This prospective, observational study was performed in 600 children from 0 to 7 yr of age. The presence or absence of nine commonly used extubation criteria in children were recorded at the time of extubation including: facial grimace, eye opening, low end-tidal anesthetic concentration, spontaneous tidal volume greater than 5 ml/kg, conjugate gaze, purposeful movement, movement other than coughing, laryngeal stimulation test, and oxygen saturation. Extubations were graded as Successful, Intervention Required, or Major Intervention Required using a standard set of criteria. The Intervention Required and Major Intervention Required outcomes were combined as a single outcome for analysis of predictors of success. Results Successful extubation occurred in 92.7% (556 of 600) of cases. Facial grimace odds ratio, 1.93 (95% CI, 1.03 to 3.60; P = 0.039), purposeful movement odds ratio, 2.42 (95% CI, 1.14 to 5.12; P = 0.022), conjugate gaze odds ratio, 2.10 (95% CI, 1.14 to 4.01; P = 0.031), eye opening odds ratio, 4.44 (95% CI, 1.06 to 18.64; P= 0.042), and tidal volume greater than 5 ml/kg odds ratio, 2.66 (95% CI, 1.21 to 5.86; P = 0.015) were univariately associated with the Successful group. A stepwise increase in any one, in any order, of these five predictors being present, from one out of five and up to five out of five yielded an increasing positive predictive value for successful extubation of 88.3% (95% CI, 82.4 to 94.3), 88.4% (95% CI, 83.5 to 93.3), 96.3% (95% CI, 93.4 to 99.2), 97.4% (95% CI, 94.4 to 100), and 100% (95% CI, 90 to 100). Conclusions Conjugate gaze, facial grimace, eye opening, purposeful movement, and tidal volume greater than 5 ml/kg were each individually associated with extubation success in pediatric surgical patients after volatile anesthetic. Further, the use of a multifactorial approach using these predictors, may lead to a more rational and robust approach to successful awake extubation.

Background and objectivesIt is unclear whether the presence of albuminuria modifies the effects of intensive systolic BP control on risk of eGFR decline, cardiovascular events, or mortality.Design, setting, participants, & measurementsThe Systolic Blood Pressure Intervention Trial randomized nondiabetic adults ≥50 years of age at high cardiovascular risk to a systolic BP target of <120 or <140 mm Hg, measured by automated office BP. We compared the absolute risk differences and hazard ratios of ≥40% eGFR decline, the Systolic Blood Pressure Intervention Trial primary cardiovascular composite outcome, and all-cause death in those with or without baseline albuminuria (urine albumin-creatinine ratio ≥30 mg/g).ResultsOver a median follow-up of 3.1 years, 69 of 1723 (4%) participants with baseline albuminuria developed ≥40% eGFR decline compared with 61 of 7162 (1%) participants without albuminuria. Incidence rates of ≥40% eGFR decline were higher in participants with albuminuria (intensive, 1.74 per 100 person-years; standard, 1.17 per 100 person-years) than in participants without albuminuria (intensive, 0.48 per 100 person-years; standard, 0.11 per 100 person-years). Although effects of intensive BP lowering on ≥40% eGFR decline varied by albuminuria on the relative scale (hazard ratio, 1.48; 95% confidence interval, 0.91 to 2.39 for albumin-creatinine ratio ≥30 mg/g; hazard ratio, 4.55; 95% confidence interval, 2.37 to 8.75 for albumin-creatinine ratio <30 mg/g; P value for interaction <0.001), the absolute increase in ≥40% eGFR decline did not differ by baseline albuminuria (incidence difference, 0.38 events per 100 person-years for albumin-creatinine ratio ≥30 mg/g; incidence difference, 0.58 events per 100 person-years for albumin-creatinine ratio <30 mg/g; P value for interaction =0.60). Albuminuria did not significantly modify the beneficial effects of intensive systolic BP lowering on cardiovascular events or mortality evaluated on relative or absolute scales.ConclusionsAlbuminuria did not modify the absolute benefits and risks of intensive systolic BP lowering.

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Background Emergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy. Methods The blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical analysis of plasma proteomics used independent sample t tests, correlations, linear regression, and robust regression models to determine network signaling and predictors of clinical outcomes. Data and network analyses were performed using IBM SPSS Statistics, SAS v 9.4, and STRING V11. Results Increased systemic (p<0.001) and intracranial (p=0.013) levels of VCAM1 were associated with the presence of hypertension. Intracranial VCAM1 was positively correlated to both infarct volume (p=0.032; r=0.34) and edema volume (p=0.026; r=0.35). The %∆ in NIHSS from admittance to discharge was found to be significantly correlated to both systemic (p=0.013; r = −0.409) and intracranial (p=0.011; r = −0.421) VCAM1 levels indicating elevated levels of systemic and intracranial VCAM1 are associated with reduced improvement of stroke severity based on NIHSS from admittance to discharge. STRING-generated analyses identified biologic functional descriptions as well as function-associated proteins from the predictive models of infarct and edema volume. Conclusions The current study provides novel data on systemic and intracranial VCAM1 in relation to stroke comorbidities, stroke severity, functional outcomes, and the role VCAM1 plays in complex protein-protein signaling pathways. These data will allow future studies to develop predictive biomarkers and proteomic targets for drug development to improve our ability to treat a devastating pathology.

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