Exploring the validity and reliability of online assessment for conversational, narrative, and expository discourse measures in school-aged children

The COVID-19 pandemic has created novel challenges in the assessment of children's speech and language. Collecting valid data is crucial for researchers and clinicians, yet the evidence on how data collection procedures can validly be adapted to an online format is sparse. The urgent need for online assessments has highlighted possible the barriers such as testing reliability and validity that clinicians face during implementation. The present study describes the adapted procedures for on-line assessments and compares the outcomes for monolingual and bilingual children of online and in-person testing using conversational, narrative and expository discourse samples and a standardized vocabulary test. A sample of 127 (103 in-person, 24 online) English monolinguals and 78 (53 in-person, 25 online) simultaneous French-English bilinguals aged 7–12 years were studied. Discourse samples were analyzed for productivity, proficiency, and syntactic complexity. MANOVAs were used to compare on-line and in-person testing contexts and age in two monolingual and bilingual school-age children. No differences across testing contexts were found for receptive vocabulary or narrative discourse. However, some modality differences were found for conversational and expository. The results from the study contribute to understanding how clinical assessment can be adapted for online format in school-aged children

Preexisting memory CD4+ T cells contribute to the primary response in an HIV-1 vaccine trial

Naive and memory CD4+ T cells reactive with human immunodeficiency virus type 1 (HIV-1) are detectable in unexposed, unimmunized individuals. The contribution of preexisting CD4+ T cells to a primary immune response was investigated in 20 HIV-1–seronegative volunteers vaccinated with an HIV-1 envelope (Env) plasmid DNA prime and recombinant modified vaccinia virus Ankara (MVA) boost in the HVTN 106 vaccine trial (clinicaltrials.gov NCT02296541). Prevaccination naive or memory CD4+ T cell responses directed against peptide epitopes in Env were identified in 14 individuals. After priming with DNA, 40% (8/20) of the elicited responses matched epitopes detected in the corresponding preimmunization memory repertoires, and clonotypes were shared before and after vaccination in 2 representative volunteers. In contrast, there were no shared epitope specificities between the preimmunization memory compartment and responses detected after boosting with recombinant MVA expressing a heterologous Env. Preexisting memory CD4+ T cells therefore shape the early immune response to vaccination with a previously unencountered HIV-1 antigen

Does ‘Animal Fun’ improve aiming and catching, and balance skills in young children?

© 2018 Elsevier Ltd Aim: The Animal Fun program, a universal early intervention program that aims to promote the motor skills and social-emotional development of young children, has shown to improve overall motor proficiency and social and behavioural outcomes. The aim of the current study was to evaluate the program's impact on children's aiming and catching, and balance skills. Methods: A cluster randomised control trial was employed, with six intervention and six control (following normal curriculum) schools. A total sample of 511 children (257 boys and 254 girls), aged 4–6 years presented at pre-test. Children were tested across three time points, pre-test, post intervention (six months later) and follow-up (18 months after pre-test), using the Movement Assessment Battery for Children-2 Aiming and Catching, and Balance tasks. The study also tested for potential moderators including pre-test motor proficiency, age, gender, and cognitive performance. Results: Participation in Animal Fun improved children's one leg balance at post-test and follow-up compared to control children, regardless of pre-test motor proficiency, age, gender, or pre-test cognitive performance. Participation in Animal Fun also improved throwing skills for those children with poorer motor proficiency compared to the controls with poorer motor performance. Interestingly, it was found that the control group's catching skills improved more than the intervention group at follow up. Conclusions: The study provides some promising results regarding the efficacy of the Animal Fun program in improving one-leg balance for all children, and throwing skills for those children with poorer motor proficiency, while also suggesting potential confounding factors, such as maturational issues and other individual factors (e.g., a child's participation in extracurricular activity)

Kenhub Atlas of Human Anatomy

<p>This atlas represents a collection of clear, comprehensible and didactically valuable images from Kenhub.com, intuitively organized to aid you in your mastery of the organization of the human body. The features of this modern print atlas were formulated by direct input from students of anatomy and experienced educators. This print atlas was designed by the preferences of anatomy students to assist in the challenges of identifying structures in the anatomy laboratory and to assist in studying for written exams.</p&gt

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection

Association of Sex With Frequent and Mild ABCA4 Alleles in Stargardt Disease

IMPORTANCE The mechanisms behind the phenotypic variability and reduced penetrance in autosomal recessive Stargardt disease (STGD1), often a blinding disease, are poorly understood. Identification of the unknown disease modifiers can improve patient and family counseling and provide valuable information for disease management. OBJECTIVE To assess the association of incompletely penetrant ABCA4 alleles with sex in STGD1. DESIGN, SETTING, AND PARTICIPANTS Genetic data for this cross-sectional study were obtained from 2 multicenter genetic studies of 1162 patients with clinically suspected STGD1. Unrelated patients with genetically confirmed STGD1 were selected. The data were collected from June 2016 to June 2019, and post hoc analysis was performed between July 2019 and January 2020. MAIN OUTCOMES AND MEASURES Penetrance of reported mild ABCA4 variants was calculated by comparing the allele frequencies in the general population (obtained from the Genome Aggregation Database) with the genotyping data in the patient population (obtained from the ABCA4 Leiden Open Variation Database). The sex ratio among patients with and patients without an ABCA4 allele with incomplete penetrance was assessed. RESULTS A total of 550 patients were included in the study, among which the mean (SD) age was 45.7 (18.0) years and most patients were women (311 [57%]). Five of the 5 mild ABCA4 alleles, including c.5603A>T and c.5882G>A, were calculated to have incomplete penetrance. The women to men ratio in the subgroup carrying c.5603A>T was 1.7 to 1; the proportion of women in this group was higher compared with the subgroup not carrying a mild allele (difference, 13%; 95% CI, 3%-23%; P=.02). The women to men ratio in the c.5882G>A subgroup was 2.1 to 1, and the women were overrepresented compared with the group carrying no mild allele (difference, 18%; 95% CI, 6%-30%; P=.005). CONCLUSIONS AND RELEVANCE This study found an imbalance in observed sex ratio among patients harboring a mild ABCA4 allele, which concerns approximately 25% of all patients with STGD1, suggesting that STGD1 should be considered a polygenic or multifactorial disease rather than a disease caused by ABCA4 gene mutations alone. The findings suggest that sex should be considered as a potential disease-modifying variable in both basic research and clinical trials on STGD1

Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes.

Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8% of patients were considered genetically explained by 460 different variants in 49 distinct genes of which 73 were novel variants, with some affecting splicing. The top five most frequent causative genes were ABCA4 (37.2%), PRPH2 (6.7%), CDHR1 (6.1%), PROM1 (4.3%) and RP1L1 (3.1%). Interestingly, variants with incomplete penetrance were revealed in almost one-third of patients considered solved (28.1%), and therefore, a proportion of patients may not be explained solely by the variants reported. This includes eight previously reported variants with incomplete penetrance in addition to CDHR1:c.783G>A and CNGB3:c.1208G>A. Notably, segregation analysis was not routinely performed for variant phasing-a limitation, which may also impact the overall diagnostic yield. The relatively high proportion of probands without any putative causal variant (60.2%) highlights the need to explore variants with incomplete penetrance, the potential modifiers of disease and the genetic overlap between iMDs and age-related macular degeneration. Our results provide valuable insights into the genetic landscape of iMDs and warrant future exploration to determine the involvement of other maculopathy genes