Observing and Identifying Hospitalist Best Communication Practices in Patient Interactions.

This study identifies actual hospitalist best communication practices that optimize patient interactions in a busy hospital context. We observed and rated 36 hospitalists and 206 patient encounters using the Kalamazoo Essential Elements of Communication Checklist-Adapted (KEECC-A). We collected descriptive statistics of checklist scores and thematically analyzed fieldnotes to identify communication patterns. Results show hospitalists score highest and most frequently use three of seven KEECC-A dimensions: builds a relationship, shares information, and gathers information. We first identify exemplar behaviors and then provide statistical comparisons by professional and hospital tenure, gender, and day of rounding observed for these three dimensions. Male hospitalists scored higher than females for shares information and significant differences were found for gender between cross-sex patient-hospitalist interactions. Hospitalists early in their professional and hospital tenure received significantly lower ratings than mid-to-late career hospitalists in the three KEECC dimensions. Hospitalists observed on the first day of rounding received significantly higher ratings than those observed on a middle or last day. We offer interpretations to explain study findings and suggest interventions to help hospitalists with less-than-desirable communication skills.

Early rearing history influences oxytocin receptor epigenetic regulation in rhesus macaques.

Adaptations to stress can occur through epigenetic processes and may be a conduit for informing offspring of environmental challenge. We employed ChIP-sequencing for H3K4me3 to examine effects of early maternal deprivation (peer-rearing, PR) in archived rhesus macaque hippocampal samples (male, n = 13). Focusing on genes with roles in stress response and behavior, we assessed the effects of rearing on H3K4me3 binding by ANOVA. We found decreased H3K4me3 binding at genes critical to behavioral stress response, the most robust being the oxytocin receptor gene OXTR, for which we observed a corresponding decrease in RNA expression. Based on this finding, we performed behavioral analyses to determine whether a gain-of-function nonsynonymous OXTR SNP interacted with early stress to influence relevant behavioral stress reactivity phenotypes (n = 194), revealing that this SNP partially rescued the PR phenotype. PR infants exhibited higher levels of separation anxiety and arousal in response to social separation, but infants carrying the alternative OXTR allele did not exhibit as great a separation response. These data indicate that the oxytocin system is involved in social-separation response and suggest that epigenetic down-modulation of OXTR could contribute to behavioral differences observed in PR animals. Epigenetic changes at OXTR may represent predictive adaptive responses that could impart readiness to respond to environmental challenge or maintain proximity to a caregiver but also contribute to behavioral pathology. Our data also demonstrate that OXTR polymorphism can permit animals to partially overcome the detrimental effects of early maternal deprivation, which could have translational implications for human psychiatric disorders.

A method to predict the impact of regulatory variants from DNA sequence.

Most variants implicated in common human disease by genome-wide association studies (GWAS) lie in noncoding sequence intervals. Despite the suggestion that regulatory element disruption represents a common theme, identifying causal risk variants within implicated genomic regions remains a major challenge. Here we present a new sequence-based computational method to predict the effect of regulatory variation, using a classifier (gkm-SVM) that encodes cell type-specific regulatory sequence vocabularies. The induced change in the gkm-SVM score, deltaSVM, quantifies the effect of variants. We show that deltaSVM accurately predicts the impact of SNPs on DNase I sensitivity in their native genomic contexts and accurately predicts the results of dense mutagenesis of several enhancers in reporter assays. Previously validated GWAS SNPs yield large deltaSVM scores, and we predict new risk-conferring SNPs for several autoimmune diseases. Thus, deltaSVM provides a powerful computational approach to systematically identify functional regulatory variants.

The rhesus macaque is three times as diverse but more closely equivalent in damaging coding variation as compared to the human.

BACKGROUND: As a model organism in biomedicine, the rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate. Although a draft genome sequence was completed in 2007, there has been no systematic genome-wide comparison of genetic variation of this species to humans. Comparative analysis of functional and nonfunctional diversity in this highly abundant and adaptable non-human primate could inform its use as a model for human biology, and could reveal how variation in population history and size alters patterns and levels of sequence variation in primates. RESULTS: We sequenced the mRNA transcriptome and H3K4me3-marked DNA regions in hippocampus from 14 humans and 14 rhesus macaques. Using equivalent methodology and sampling spaces, we identified 462,802 macaque SNPs, most of which were novel and disproportionately located in the functionally important genomic regions we had targeted in the sequencing. At least one SNP was identified in each of 16,797 annotated macaque genes. Accuracy of macaque SNP identification was conservatively estimated to be >90%. Comparative analyses using SNPs equivalently identified in the two species revealed that rhesus macaque has approximately three times higher SNP density and average nucleotide diversity as compared to the human. Based on this level of diversity, the effective population size of the rhesus macaque is approximately 80,000 which contrasts with an effective population size of less than 10,000 for humans. Across five categories of genomic regions, intergenic regions had the highest SNP density and average nucleotide diversity and CDS (coding sequences) the lowest, in both humans and macaques. Although there are more coding SNPs (cSNPs) per individual in macaques than in humans, the ratio of dN/dS is significantly lower in the macaque. Furthermore, the number of damaging nonsynonymous cSNPs (have damaging effects on protein functions from PolyPhen-2 prediction) in the macaque is more closely equivalent to that of the human. CONCLUSIONS: This large panel of newly identified macaque SNPs enriched for functionally significant regions considerably expands our knowledge of genetic variation in the rhesus macaque. Comparative analysis reveals that this widespread, highly adaptable species is approximately three times as diverse as the human but more closely equivalent in damaging variation.