Large-Scale Pharmacogenomics Analysis of Patients With Cancer Within the 100,000 Genomes Project Combining Whole-Genome Sequencing and Medical Records to Inform Clinical Practice.

Purpose: As part of the 100,000 Genomes Project, we set out to assess the potential viability and clinical impact of reporting genetic variants associated with drug-induced toxicity for patients with cancer recruited for whole-genome sequencing (WGS) as part of a genomic medicine service.

Methods: Germline WGS from 76,805 participants was analyzed for pharmacogenetic (PGx) variants in four genes (, , , ) associated with toxicity induced by five drugs used in cancer treatment (capecitabine, fluorouracil, mercaptopurine, thioguanine, irinotecan). Linking genomic data with prescribing and hospital incidence records, a phenome-wide association study (PheWAS) was performed to identify whether phenotypes indicative of adverse drug reactions (ADRs) were enriched in drug-exposed individuals with the relevant PGx variants.

One Score to Rule Them All? Comparing the Predictive and Concurrent Validity of 30 Hearts and Flowers Scoring Approaches.

The Hearts and Flowers (H&F) task is a computerized executive functioning (EF) assessment that has been used to measure EF from early childhood to adulthood. It provides data on accuracy and reaction time (RT) across three different task blocks (hearts, flowers, and mixed). However, there is a lack of consensus in the field on how to score the task that makes it difficult to interpret findings across studies.

Overlooked advantages of interactive book reading in early childhood? A systematic review and research agenda.

Previous reviews of the nature and consequences of adult-child book reading have focused on seeking impacts of interactive reading on the acquisition of vocabulary and emergent literacy skills. In this systematic review we examined to what extent there has been systematic study of the effects of interactive reading on four less frequently studied developmental outcomes important to children's academic and life prospects: socio-emotional and socio-cognitive (SEL) skills, narrative skills, grammar, and world knowledge. We identified 67 studies of interactive reading that met the inclusion criteria and that examined the targeted outcomes, using either experimental, quasi-experimental, correlational, or single-group intervention methods.

Does kindergarten instruction matter for sustaining the prekindergarten (PreK) boost? Evidence from individual- and classroom-level survey and observational data.

The sustaining environments hypothesis theorizes that the lasting effects of PreK programs are contingent on the quality of the subsequent learning environment in early elementary school. The current study tests this theory by leveraging data from students ( = 462) who did and did not enroll in the Boston Public Schools (BPS) prekindergarten (PreK) program as well as features of their kindergarten instruction measured at the child- and classroom-levels using surveys and observations. Taken together, findings revealed limited evidence for the sustaining environments hypothesis.

The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources.

Purpose: Several groups and resources provide information that pertains to the validity of gene-disease relationships used in genomic medicine and research; however, universal standards and terminologies to define the evidence base for the role of a gene in disease and a single harmonized resource were lacking. To tackle this issue, the Gene Curation Coalition (GenCC) was formed.

Methods: The GenCC drafted harmonized definitions for differing levels of gene-disease validity on the basis of existing resources, and performed a modified Delphi survey with 3 rounds to narrow the list of terms.

100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care - Preliminary Report.

Background: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.

Scaling national and international improvement in virtual gene panel curation via a collaborative approach to discordance resolution.

Clinical validity assessments of gene-disease associations underpin analysis and reporting in diagnostic genomics, and yet wide variability exists in practice, particularly in use of these assessments for virtual gene panel design and maintenance. Harmonization efforts are hampered by the lack of agreed terminology, agreed gene curation standards, and platforms that can be used to identify and resolve discrepancies at scale. We undertook a systematic comparison of the content of 80 virtual gene panels used in two healthcare systems by multiple diagnostic providers in the United Kingdom and Australia.

Beginning to Read in Vietnamese: Kindergarten Precursors to First Grade Fluency and Reading Comprehension.

Measures of decoding and oral language have been shown to predict early reading comprehension across a wide variety of languages, though the timeframe and strength of the predictions vary by orthographic depth. This study is the first to examine predictors of early reading in Vietnamese, a transparent orthography of Romanized letters and diacritics. Eighty-two children in Hanoi, Vietnam, completed measures of decoding and oral language in kindergarten (phonological awareness, PA; rapid automatized naming, RAN; receptive and expressive vocabulary) and measures of decoding and reading comprehension in first grade.

Is Skill Type the Key to the PreK Fadeout Puzzle? Differential Associations Between Enrollment in PreK and Constrained and Unconstrained Skills Across Kindergarten.

This study examines whether associations between enrollment in public and non-public PreK and children's (N = 508; M  = 5.60 years in fall of kindergarten) math and language and literacy outcomes were more likely to be sustained through the spring of kindergarten for unconstrained versus constrained skills. Associations between public PreK and language, literacy, and math outcomes were more strongly sustained through the spring of kindergarten for unconstrained skills, relative to constrained skills.

Time well spent: Home learning activities and gains in children's academic skills in the prekindergarten year.

Parental engagement in home-based learning activities is linked to children's academic skills. Yet, interventions that try to enhance parental engagement-sometimes targeted to families with low levels of education-have small effects. This study aimed to inform supports for families by examining how different types of home-based learning activities influence academic skills during prekindergarten.

Shared Book Reading in Preschool Supports Bilingual Children's Second-Language Learning: A Cluster-Randomized Trial.

This cluster-randomized controlled study examined dual language learners (DLLs) in Norway who received a book-based language intervention program. About 464 DLLs aged 3-5 years in 123 early childhood classrooms participated in the study. The children were acquiring Norwegian as their second language in preschool and spoke a variety of first languages at home.

Analyzing input quality along three dimensions: interactive, linguistic, and conceptual.

This paper provides an overview of the features of caregiver input that facilitate language learning across early childhood. We discuss three dimensions of input quality: interactive, linguistic, and conceptual. All three types of input features have been shown to predict children's language learning, though perhaps through somewhat different mechanisms.

Identifying Developmental Language Disorder in Vietnamese Children.

Purpose Developmental language disorder (DLD), defined by low language performance despite otherwise normal development, can negatively impact children's social and academic outcomes. This study is the 1st to examine DLD in Vietnamese. To lay the foundation, we identified cases of DLD in Vietnam and explored language-specific characteristics of the disorder.

ArrayExpress update - from bulk to single-cell expression data.

ArrayExpress (https://www.ebi.ac.

The BioStudies database-one stop shop for all data supporting a life sciences study.

BioStudies (www.ebi.ac.

Implementation Challenges for Tier One and Tier Two School-Based Programs for Early Adolescents.

This mixed-method study examined the implementation and the challenges to implementation for participants in randomized controlled trials of two school-based programs for early adolescents: the Tier One Word Generation (WG) program, and the Tier Two Strategic Adolescent Reading Intervention (STARI). Levels of implementation for WG and STARI varied substantially across teachers and classrooms, with mean levels of 40% for fourth- and fifth-grade WG, 31% for sixth- and seventh-grade WG, and 47% for STARI. The three most common implementation challenges for WG were lack of time, multiple new programs/curricula happening at the same time, and time lost to testing and test prep.

Expression Atlas update--an integrated database of gene and protein expression in humans, animals and plants.

Expression Atlas (http://www.ebi.ac.

Experimental impacts of a teacher professional development program in Chile on preschool classroom quality and child outcomes.

We assessed impacts on classroom quality and on 5 child language and behavioral outcomes of a 2-year teacher professional-development program for publicly funded prekindergarten and kindergarten in Chile. This cluster-randomized trial included 64 schools (child N = 1,876). The program incorporated workshops and in-classroom coaching.

Teacher-child interactions in Chile and their associations with prekindergarten outcomes.

Quality of teacher-child interactions is central to prekindergarten children's learning. In the United States, the quality of teacher-child interactions is commonly assessed using the teaching through interactions conceptual framework and an associ/ated observational tool, the Classroom Assessment Scoring System (CLASS). This study examined: (a) whether there was evidence supporting three distinctive domains of teacher-child interactions in Chile (construct validity) and (b) whether these domains predicted end-of-prekindergarten language, academic, and executive function skills in Chile (predictive validity).

Input to interaction to instruction: three key shifts in the history of child language research.

In the early years of the Journal of Child Language, there was considerable disagreement about the role of language input or adult-child interaction in children's language acquisition. The view that quantity and quality of input to language-learning children is relevant to their language development has now become widely accepted as a principle guiding advice to parents and the design of early childhood education programs, even if it is not yet uncontested in the field of language development. The focus on variation in the language input to children acquires particular educational relevance when we consider variation in access to academic language - features of language particularly valued in school and related to success in reading and writing.

Premature return to play and return to learn after a sport-related concussion: physician's chart review.

Objective: To determine what proportion of patients experience an exacerbation of their symptoms as a result of premature return to play (RTP) and return to learn (RTL) following sport-related concussions.

Design: Retrospective study of electronic medical records from the office-based practice of one family and sport medicine physician who had systematically provided recommendations for cognitive and physical rest based on existing consensus recommendations. Two blinded authors independently reviewed each chart, which included Sport Concussion Assessment Tool (SCAT) and SCAT2 symptom self-report forms to determine whether an athlete had returned to play or learn prematurely.

Do family physicians, emergency department physicians, and pediatricians give consistent sport-related concussion management advice?

Objective: To identify differences and gaps in recommendations to patients for the management of sport-related concussion among FPs, emergency department physicians (EDPs), and pediatricians.

Design: A self-administered, multiple-choice survey was e-mailed to FPs, EDPs, and pediatricians. The survey had been assessed for content validity.

Structural and functional annotation of the porcine immunome.

Background: The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems.