Admixture mapping (also known as "mapping by admixture linkage disequilibrium," or MALD) has been proposed as an efficient approach to localizing disease-causing variants that differ in frequency (because of either drift or selection) between two historically separated populations. Near a disease gene, patient populations descended from the recent mixing of two or more ethnic groups should have an increased probability of inheriting the alleles derived from the ethnic group that carries more disease-susceptibility alleles. The central attraction of admixture mapping is that, since gene flow has occurred recently in modern populations (e.g., in African and Hispanic Americans in the past 20 generations), it is expected that admixture-generated linkage disequilibrium should extend for many centimorgans. High-resolution marker sets are now becoming available to test this approach, but progress will require (a). computational methods to infer ancestral origin at each point in the genome and (b). empirical characterization of the general properties of linkage disequilibrium due to admixture. Here we describe statistical methods to estimate the ancestral origin of a locus on the basis of the composite genotypes of linked markers, and we show that this approach accurately estimates states of ancestral origin along the genome. We apply this approach to show that strong admixture linkage disequilibrium extends, on average, for 17 cM in African Americans. Finally, we present power calculations under varying models of disease risk, sample size, and proportions of ancestry. Studying approximately 2500 markers in approximately 2500 patients should provide power to detect many regions contributing to common disease. A particularly important result is that the power of an admixture mapping study to detect a locus will be nearly the same for a wide range of mixture scenarios: the mixture proportion should be 10%-90% from both ancestral populations.

A variety of mechanical and laser-based methods remove or shift atherosclerotic plaques and reopen the artery to its original lumen. Subsequent treatment with drug-coated balloons (DCB) may smooth the vessel wall but does not require high-pressure inflation. We investigated the efficacy of paclitaxel-coated balloons inflated with only 2 atm after bare metal stent implantation in coronary arteries of 24 pigs. Angiography and histomorphometry was performed on day 28. DCB inflated with 2 atm caused similar reduction of late lumen loss (LLL) as high-pressure inflation with 12 atm (0.89 ± 0.58 vs. 0.72 ± 0.39 mm, p = 0.34). Both DCB treatments significantly (p < 0.01) reduced LLL versus uncoated balloons (1.50 ± 0.51 mm). Treatment with low-pressure DCB resulted in less maximal intimal thickness (0.45 ± 0.15 vs. 0.67 ± 0.25 mm) and neointimal area (2.93 ± 0.73 vs. 3.82 ± 1.27 mm(2)) than treatment with uncoated balloons (p < 0.05). In conclusion, low-pressure treatment with DCB was similarly effective as high-pressure treatment justifying clinical trials in vessels which will benefit from inhibition of neointimal proliferation but may not tolerate high inflation pressure.

Objective: Children and adolescents with neurodevelopmental disorders often report disturbances in autonomic nervous system (ANS) related behavioral regulation such as sensory sensitivity, anxiety, and emotion dysregulation. Cranial electrotherapy stimulation (CES) is a method of non-invasive transcranial current stimulation presumed to modify behavioral regulation abilities via ANS modulation. Methods: To begin to address this knowledge gap, we examined the feasibility and preliminary efficacy of a 4-week CES intervention on behavioral regulation in a mixed neurodevelopmental sample of children and adolescents currently receiving care at clinical centers operated by Cortica. We first aimed to evaluate adherence, side effects, and tolerance of CES device use. Second, we aimed to evaluate pre-post change in three PNS-associated behavioral regulation conditions: sensory sensitivities, emotion dysregulation, and anxiety. Results: Feasibility results demonstrated moderate adherence, tolerability, and satisfaction with CES usage. Further, preliminary efficacy results demonstrated a significant reduction in sensory sensitivity, anxiety, and emotion dysregulation. Conclusion: Results from this pilot study provide justification for future randomized control trials using CES in children and adolescents with behavioral dysregulation.

The purpose of this study was to examine the effects of a medically centered, interdisciplinary treatment model on adaptive behavior in children with Autism Spectrum Disorder (ASD). The Cortica model involves a comprehensive program including behavioral and developmental therapies, overseen by a neurodevelopmental physician. We investigated the research question, how do adaptive behaviors change over time during care at Cortica? We analyzed change in the Vineland Adaptive Behavior Scales, Third Edition, over the course of Cortica care compared to standard care, represented by longitudinal data from the National Database for Autism Research (NDAR). Using propensity score weights to match cohorts based on baseline functioning, multilevel growth curve models showed significant Cohort × Time interactions for the Adaptive Behavior Composite score and all subscale scores, indicating increased growth in adaptive behavior skills for children in the Cortica cohort relative to NDAR.Results of this study highlight the importance of using adaptive behaviors as a primary outcome in clinical research studies.