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Monogenic disorders account for a large proportion of population-attributable risk for neurodevelopmental disabilities. However, the data necessary to infer a causal relationship between a given genetic variant and a particular neurodevelopmental disorder is often lacking. Recognizing this scientific roadblock, 13 Intellectual and Developmental Disabilities Research Centers (IDDRCs) formed a consortium to create the Brain Gene Registry (BGR), a repository pairing clinical genetic data with phenotypic data from participants with variants in putative brain genes. Phenotypic profiles are assembled from the electronic health record (EHR) and a battery of remotely administered standardized assessments collectively referred to as the Rapid Neurobehavioral Assessment Protocol (RNAP), which include cognitive, neurologic, and neuropsychiatric assessments, as well as assessments for attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Co-enrollment of BGR participants in the Clinical Genome Resource's (ClinGen's) GenomeConnect enables display of variant information in ClinVar. The BGR currently contains data on 479 participants who are 55% male, 6% Asian, 6% Black or African American, 76% white, and 12% Hispanic/Latine. Over 200 genes are represented in the BGR, with 12 or more participants harboring variants in each of these genes: CACNA1A, DNMT3A, SLC6A1, SETD5, and MYT1L. More than 30% of variants are de novo and 43% are classified as variants of uncertain significance (VUSs). Mean standard scores on cognitive or developmental screens are below average for the BGR cohort. EHR data reveal developmental delay as the earliest and most common diagnosis in this sample, followed by speech and language disorders, ASD, and ADHD. BGR data has already been used to accelerate gene-disease validity curation of 36 genes evaluated by ClinGen's BGR Intellectual Disability (ID)-Autism (ASD) Gene Curation Expert Panel. In summary, the BGR is a resource for use by stakeholders interested in advancing translational research for brain genes and continues to recruit participants with clinically reported variants to establish a rich and well-characterized national resource to promote research on neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

BackgroundThe Government of Ontario, Canada, announced hospital funding reforms in 2011, including Quality-based Procedures (QBPs) involving pre-set funds for managing patients with specific diagnoses/procedures. A key goal was to improve quality of care across the jurisdiction.MethodsInterrupted time series evaluated the policy change, focusing on four QBPs (congestive heart failure, hip fracture surgery, pneumonia, prostate cancer surgery), on patients hospitalized 2010-2017. Outcomes included return to hospital or death within 30 days, acute length of stay (LOS), volume of admissions, and patient characteristics.ResultsAt 2 years post-QBPs, the percentage of hip fracture patients who returned to hospital or died was 3.13% higher in absolute terms (95% CI: 0.37% to 5.89%) than if QBPs had not been introduced. There were no other statistically significant changes for return to hospital or death. For LOS, the only statistically significant change was an increase for prostate cancer surgery of 0.33 days (95% CI: 0.07 to 0.59). Volume increased for congestive heart failure admissions by 80 patients (95% CI: 2 to 159) and decreased for hip fracture surgery by 138 patients (95% CI: -183 to -93) but did not change for pneumonia or prostate cancer surgery. The percentage of patients who lived in the lowest neighborhood income quintile increased slightly for those diagnosed with congestive heart failure (1.89%; 95% CI: 0.51% to 3.27%) and decreased for those who underwent prostate cancer surgery (-2.08%; 95% CI: -3.74% to -0.43%).InterpretationThis policy initiative involving a change to hospital funding for certain conditions was not associated with substantial, jurisdictional-level changes in access or quality.

The purpose of this study was to examine the development of phonological awareness (PA) skills among Hebrew-speaking kindergarten children. Specifically, the study examines the effects of cognitive, early literacy, and language skills to PA among Hebrew-speaking children at the middle (Early K) and end (End K) of kindergarten, and the contribution of various literacy and cognitive skills measured from the early kindergarten stage to the subsequent development of PA. Participants were 41 native Hebrew-speaking children (28 boys), ages 5–6, who were recruited from two kindergarten classrooms. A battery of cognitive, early literacy, and language measures was administered and ten PA skills were examined extensively. The results demonstrated the rapid growth of PA skills from Early K to End K. The participants were significantly better at manipulations at the syllable level, as compared to phonemes or consonants. Furthermore, deletion of a final consonant was found to be easier for them than deletion of an initial consonant. This finding emphasizes the body-coda segmentation tendency, which characterizes the Hebrew language structure. Strong-moderate positive correlations were found between PA and both letter naming and executive functioning at Early K. A strong correlation between letter naming and PA was found at End K. Regression analyses demonstrated that letter naming and executive functioning at Early K were the most significant predictors of PA at Early K, and that letter naming was the most significant predictor at End K. These findings highlight both universal and language-specific features of phonological awareness.

HITLER, STALIN, MUM & DAD A family memoir of miraculous survival DANIEL FINKELSTEIN 496pp. William Collins. 25 [pounds sterling]. Russia, unlike Germany , has never come to terms squarely with [...]

Costs of implementing genomic testing innovations extend beyond the cost of sequencing, affecting personnel and infrastructure for which little data are available. We developed a time and motion (T&M) study within the Clinical Sequencing Evidence‐Generating Research (CSER) consortium to address this gap, and herein describe challenges of conducting T&M studies within a research consortium and the approaches we developed to overcome them. CSER investigators created a subgroup to carry out the T&M study (authors). We describe logistical and administrative challenges associated with resource use data collection across heterogeneous projects conducted in real‐world clinical settings, and our solutions for completing this study and harmonizing data across projects. We delineate processes for feasible data collection on workflow, personnel, and resources required to deliver genetic testing innovations in each CSER project. A critical early step involved developing detailed project‐specific process flow diagrams of innovation implementation in projects' clinical settings. Analyzing diagrams across sites, we identified common process‐step themes, used to organize project‐specific data collection and cross‐project analysis. Given the heterogeneity of innovations, study design, and workflows, which affect resources required to deliver genetic testing innovations, flexibility was necessary to harmonize data collection. Despite its challenges, this heterogeneity provides rich insights about variation in clinical processes and resource implications for implementing genetic testing innovations. [ABSTRACT FROM AUTHOR]