A prospective genome-wide study of prostate cancer metastases reveals association of wnt pathway activation and increased cell cycle proliferation with primary resistance to abiraterone acetate-prednisone.

Background: Genomic aberrations have been identified in metastatic castration-resistant prostate cancer (mCRPC), but molecular predictors of resistance to abiraterone acetate/prednisone (AA/P) treatment are not known. Patients and methods: In a prospective clinical trial, mCRPC patients underwent whole-exome sequencing (n = 82) and RNA sequencing (n = 75) of metastatic biopsies before initiating AA/P with the objective of identifying genomic alterations associated with resistance to AA/P. Primary resistance was determined at 12 weeks of treatment using criteria for progression that included serum prostate-specific antigen measurement, bone and computerized tomography imaging and symptom assessments. Acquired resistance was determined using the end point of time to treatment change (TTTC), defined as time from enrollment until change in treatment from progressive disease. Associations of genomic and transcriptomic alterations with primary resistance were determined using logistic regression, Fisher's exact test, single and multivariate analyses. Cox regression models were utilized for determining association of genomic and transcriptomic alterations with TTTC. Results: At 12 weeks, 32 patients in the cohort had progressed (nonresponders). Median study follow-up was 32.1 months by which time 58 patients had switched treatments due to progression. Median TTTC was 10.1 months (interquartile range: 4.4-24.1). Genes in the Wnt/ß-catenin pathway were more frequently mutated and negative regulators of Wnt/ß-catenin signaling were more frequently deleted or displayed reduced mRNA expression in nonresponders. Additionally, mRNA expression of cell cycle regulatory genes was increased in nonresponders. In multivariate models, increased cell cycle proliferation scores (≥ 50) were associated with shorter TTTC (hazard ratio = 2.11, 95% confidence interval: 1.17-3.80; P = 0.01). Conclusions: Wnt/ß-catenin pathway activation and increased cell cycle progression scores can serve as molecular markers for predicting resistance to AA/P therapy.

Development and acceptability of a video-based vaccine promotion tutorial for obstetric care providers.

A prenatal care provider's recommendation for maternal vaccines is one of the strongest predictors of vaccine acceptance during pregnancy. Aside from basic talking points, few resources exist to help obstetric care providers effectively navigate conversations with vaccine hesitant patients. This paper describes the development and acceptability of "VaxChat," an hour-long, evidence-based video tutorial aimed at improving obstetric care providers' ability to promote maternal vaccines. Between June and November 2017, 62 obstetric care providers registered to receive continuing medical education credit for viewing VaxChat. Of the post-tutorial responses received, over 90% said VaxChat increased their knowledge of what to say to vaccine hesitant patients, increased their confidence in addressing vaccinations with their pregnant patients, and will help them improve their practice culture regarding maternal vaccine promotion. Eighty percent intend to change how they approach vaccine conversations. These data suggest VaxChat may be a welcome complement to existing provider-to-patient talking points.

Ballistocardiogram artifact reduction in the simultaneous acquisition of auditory ERPS and fMRI.

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are now being combined to analyze brain function. Confounding the EEG signal acquired in the MR environment is a ballistocardiogram artifact (BA), which is predominantly caused by cardiac-related body movement. The objective of this study was to develop and evaluate a method for reducing these MR-induced artifacts to retrieve small auditory event-related potentials (ERPs) from EEG recorded during fMRI. An algorithm for BA reduction was developed that relies on timing information obtained from simultaneous electrocardiogram (ECG) recordings and subsequent creation of an adaptive BA template. The BA template is formed by median-filtering 10 consecutive BA events in the EEG signal. The continuously updated template is then subtracted from each BA in the EEG. The auditory ERPs are obtained through signal averaging of the remaining EEG signal. Experimental and simulated ERP data were estimated to assess effectiveness of the BA reduction. Simulation showed that the algorithm reduced BA without significantly altering the morphology of a signal periodically inserted in the EEG. Auditory ERP data, obtained in a 1.5-T scanner during a passive auditory oddball paradigm and processed with the BA reduction algorithm, were comparable to data recorded in a mock scanner outside the magnetic field with the same experimental paradigm. It is concluded that through adequate reduction of the BA, relatively small auditory ERPs can be acquired in the MR environment.