Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain.

The mammalian brain is composed of diverse, specialized cell populations. To systematically ascertain and learn from these cellular specializations, we used Drop-seq to profile RNA expression in 690,000 individual cells sampled from 9 regions of the adult mouse brain. We identified 565 transcriptionally distinct groups of cells using computational approaches developed to distinguish biological from technical signals. Cross-region analysis of these 565 cell populations revealed features of brain organization, including a gene-expression module for synthesizing axonal and presynaptic components, patterns in the co-deployment of voltage-gated ion channels, functional distinctions among the cells of the vasculature and specialization of glutamatergic neurons across cortical regions. Systematic neuronal classifications for two complex basal ganglia nuclei and the striatum revealed a rare population of spiny projection neurons. This adult mouse brain cell atlas, accessible through interactive online software (DropViz), serves as a reference for development, disease, and evolution.

Insights into variation in meiosis from 31,228 human sperm genomes.

Meiosis, although essential for reproduction, is also variable and error-prone: rates of chromosome crossover vary among gametes, between the sexes, and among humans of the same sex, and chromosome missegregation leads to abnormal chromosome numbers (aneuploidy)1-8. To study diverse meiotic outcomes and how they covary across chromosomes, gametes and humans, we developed Sperm-seq, a way of simultaneously analysing the genomes of thousands of individual sperm. Here we analyse the genomes of 31,228 human gametes from 20 sperm donors, identifying 813,122 crossovers and 787 aneuploid chromosomes. Sperm donors had aneuploidy rates ranging from 0.01 to 0.05 aneuploidies per gamete; crossovers partially protected chromosomes from nondisjunction at the meiosis I cell division. Some chromosomes and donors underwent more-frequent nondisjunction during meiosis I, and others showed more meiosis II segregation failures. Sperm genomes also manifested many genomic anomalies that could not be explained by simple nondisjunction. Diverse recombination phenotypes-from crossover rates to crossover location and separation, a measure of crossover interference-covaried strongly across individuals and cells. Our results can be incorporated with earlier observations into a unified model in which a core mechanism, the variable physical compaction of meiotic chromosomes, generates interindividual and cell-to-cell variation in diverse meiotic phenotypes.

Electronic Fetal Monitoring Credentialing Examination: The First 4000.

Objective Recognized variability in fetal heart rate interpretation led the Perinatal Quality Foundation (PQF) to develop a credentialing exam. We report an evaluation of the 1st 4000 plus PQF Fetal Monitoring Credentialing (FMC) exams. Study Design The PQF FMC exam is an online assessment for obstetric providers and nurses. The exam contains two question types: traditional multiple-choice evaluating knowledge and Script Concordance Theory (SCT) evaluating judgment. Reliability was measured through McDonald's Total Omega and Cronbach's Alpha. Pearson's correlations between knowledge and judgment were measured. Results From February 2014 through September 2018, 4,330 different individuals took the exam. A total of 4,057 records were suitable for reliability analysis: 2,105 (52%) physicians, 1,756 (43%) nurses, and 196 (5%) certified nurse midwives (CNMs). As a measure of test reliability, total Omega was 0.80 for obstetric providers and 0.77 for nurses. There was only moderate correlation between the knowledge scores and judgment scores for obstetric providers (0.38) and for nurses (0.43). Conclusion The PQF FMC exam is a reliable, valid assessment of both Electronic Fetal Monitoring (EFM) knowledge and judgment. It evaluates essential EFM skills for the establishment of practical credentialing. It also reports modest correlation between knowledge and judgment scores, suggesting that knowledge alone does not assure clinical competency.