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High dimensional neuroimaging datasets and machine learning have been used to estimate and predict domain-specific cognition, but comparisons with simpler models composed of easy-to-measure variables are limited. Regularization methods in particular may help identify regions-of-interest related to domain-specific cognition. Using data from the Northern Manhattan Study, a cohort study of mostly Hispanic older adults, we compared three models estimating domain-specific cognitive performance: sociodemographics and APOE ε4 allele status (basic model), the basic model and MRI markers, and a model with only MRI markers. We used several machine learning methods to fit our regression models: elastic net, support vector regression, random forest, and principal components regression. Model performance was assessed with the RMSE, MAE, and R 2 statistics using 5-fold cross-validation. To assess whether prediction models with imaging biomarkers were more predictive than prediction models built with randomly generated biomarkers, we refit the elastic net models using 1000 datasets with random biomarkers and compared the distribution of the RMSE and R 2 in models using these random biomarkers to the RMSE and R 2 from observed models. Basic models explained ~ 31-38% of the variance in domain-specific cognition. Addition of MRI markers did not improve estimation. However, elastic net models with only MRI markers performed significantly better than random MRI markers (one-sided P < .05) and yielded regions-of-interest consistent with previous literature and others not previously explored. Therefore, structural brain MRI markers may be more useful for etiological than predictive modeling., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There are substantial differences in the effects of blood pressure (BP) medications in individual patients. Yet, the current standard approach to prescribing BP medications is not personalized., Objective: To determine the feasibility of individualizing the selection of BP medications through pragmatic personalized (i.e., N-of-1) trials., Design: Series of N-of-1 trials., Setting: Outpatient., Patients: Hypertensive adults prescribed none or one BP medication., Intervention: Participation in a flexible, open-label personalized trial of two to three BP medications (NCT02744456)., Measurements: BP was measured twice per day with a validated home BP device. Frequency and severity of side effects were assessed at the end of the day via an electronic questionnaire. Patients' BP medication preference was assessed after reviewing BP lowering and side effect results with a study clinician. Feasibility was assessed by determining the proportion of patients who adhered to self-assessments. Benefit was assessed by asking patients to rate the helpfulness of participation and whether they would recommend personalized trials to other hypertensive patients., Key Results: Of ten patients enrolled, two dropped out prior to initiation, one discovered white coat hypertension through ambulatory BP monitoring, and seven (mean age 58 years, 71% of women) completed personalized trials. All seven were compliant with home BP monitoring and side effect tracking. All seven recommended personalized trials of BP medications to others. Thiazides were preferred by three patients, renin-angiotensin system-blocking agents by two patients, a combination of thiazide and beta-blocker by one patient, and any of three classes by one patient., Conclusions: Personalized trials of BP medications were feasible and led to improved treatment precision. Heterogeneity of patient preferences and of therapeutic BP response for first-line BP medications can be determined through a personalized trial approach.

Background: Previous studies of exercise have focused on measuring physical activity in totality using summary statistics such as metabolic equivalent score for total intensity or total energy count., Objective: We aimed to examine the multidimensionality of leisure-time physical activity (LTPA) and to identify the specific LTPA components that were associated with cardiovascular mortality in the elderly., Design and Participants: The Northern Manhattan Study (NOMAS) is a multiethnic prospective cohort of elderly stroke-free individuals consisting of a total of 3298 participants recruited between 1993 and 2001, with a median follow-up of 17 years., Main Measures: Physical activity questionnaire data were available in 3293 NOMAS participants, who were categorized into subgroups with similar exercise patterns by model-based cluster analysis. Three subgroup-defining LTPA features were identified and were considered as primary exposures in Cox proportional hazard models: frequency of activity, number of activity types (variety), and energy-to-duration ratio (EDR). We considered cardiovascular mortality and non-cardiovascular mortality as outcomes in Cox cause-specific proportional hazard models, and all-cause mortality as outcome in Cox models., Key Results: A high activity frequency was associated with reduced cardiovascular mortality (hazard ratio, HR = 0.93, P = 0.03), but demonstrated no effect on non-cardiovascular death. A high EDR was associated with increased risk of cardiovascular death (HR = 1.30, P = 0.01). A high number of activity types was beneficial in reducing all-cause mortality (HR = 0.87, P = 0.01)., Conclusions: Exercise frequency was protective against cardiovascular mortality, and a high variety of activity was protective against all-cause mortality. The performance of frequent and varied non-intense exercise in an elderly population such as ours is achievable and can reduce the risk of death., Competing Interests: The authors declare that they have no conflict of interest. Funding/Support This study was supported by the National Institutes of Health grants R01 HL111195 (Cheung/Elkind), NS K23073104 (Willey), and R01 NS029993 (Sacco/Elkind). Role of the Funder/Sponsor The funding source had no role in the design and conduct of the study with regard to the collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

A meta-analysis was performed to examine differences in IQ profiles between individuals with Asperger's disorder (AspD) and high-functioning autism (HFA). Fifty-two studies were included for this study. The results showed that (a) individuals with AspD had significantly higher full-scale IQ, verbal IQ (VIQ), and performance IQ (PIQ) than did individuals with HFA; (b) individuals with AspD had significantly higher VIQ than PIQ; and (c) VIQ was similar to PIQ in individuals with HFA. These findings seem to suggest that AspD and HFA are two different subtypes of Autism. The implications of the present findings to DSM-5 Autism Spectrum Disorder are discussed.

This study aimed to identify the factors associated with participation in employment for high school leavers with autism. A secondary data analysis of the National Longitudinal Transition Study 2 (NLTS2) data was performed. Potential factors were assessed using a weighted multivariate logistic regression. This study found that annual household income, parental education, gender, social skills, whether the child had intellectual disability, whether the child graduated from high school, whether the child received career counseling during high school, and whether the child's school contacted postsecondary vocational training programs or potential employers were the significant factors associated with participation in employment. These findings may have implications for professionals who provide transition services and post-secondary programs for individuals with autism.

This exploratory study was designed to identify the factors predictive of participation in postsecondary education for high school leavers with autism. A secondary data analysis of the National Longitudinal Transition Study 2 (NLTS2) data was performed for this study. Potential predictors of participation in postsecondary education were assessed using a backward logistic regression analysis. This study found that the high school's primary post-high school goal for the student, parental expectations, high school type, annual household income, and academic performance were significant predictors of participation in postsecondary education. The findings of this current study may provide critical information for parents of children with autism as well as educators and professionals who work with students with autism.

Background: P-glycoprotein (Pgp) mediates, in part, resistance to natural product chemotherapy drugs which constitute over half of the available drugs for cancer treatment. Tamoxifen (TAM) enhances intracellular deposition of natural product chemotherapy in human cell lines by inhibition of Pgp. Pgp is highly expressed in the choroid plexus and is thought to be a key component of the blood-cerebrospinal fluid barrier (BCSFB). We conducted a prospective, randomized study to assess if Pgp inhibition by TAM alters deposition of paclitaxel in cerebrospinal fluid (CSF)., Methods: Ten patients with either primary or metastatic brain tumors were randomized to: paclitaxel alone (175 mg/m2/IV) or a course of TAM (160 mg/m2 PO BID on Days 1-5) followed by paclitaxel (175 mg/m2/IV on Day 5). CSF and plasma samples were obtained following paclitaxel infusion; paclitaxel and TAM concentrations were measured by high-performance liquid chromatography assays., Results: Paclitaxel was detected in the CSF of six of the 10 patients. Peak CSF paclitaxel concentrations of the paclitaxel and paclitaxel-TAM groups ranged between 3.5-57.4 and 2.3-24.6 nM, respectively. Though there was a 2.4-fold higher mean CSF paclitaxel concentration and a 3.7-fold higher median peak CSF:plasma paclitaxel ratio for those who received paclitaxel alone as compared to combined paclitaxel-TAM, it was not statistically significant (P = 0.22). In one patient enrolled to both arms, higher CSF concentrations of paclitaxel and higher paclitaxel CSF: plasma ratios were observed when given paclitaxel alone., Conclusions: The trend towards lower paclitaxel CSF concentrations when given with TAM is consistent with the published finding that Pgp's localization in the endothelial cells of the choroid plexus works in an opposite direction and keeps drugs in the CSF. Thus, agents which inhibit Pgp, such as TAM, may increase efflux of Pgp substrates out of the BCSFB and may paradoxically lower CSF concentrations of natural product chemotherapy drugs. Conceptually, this finding implies that the Pgp in the BBB and BCSFB keeps natural toxins such as paclitaxel, from entering the brain (BBB) and, if they do enter the brain, keeps them in the CSF (BCSFB) where they may be less harmful than if they re-entered the brain. Thus, our work supports this novel idea and adds to the understanding of the functions of the BCSFB.