Mild Intellectual Disability at the Postsecondary Level: Results of a Survey of Disability Service Offices

Disability Service Staff at colleges and universities in Ontario, Canada were sur-veyed regarding the number of students arriving at their offices with the label of mild intellectual disability. Information was obtained regarding criteria used in association with this label, documentation required to support the classification, and accommodations provided, as well as the types of programs in which these students enroll and their success in those programs. Results demonstrate little consistency across institutions regarding the criteria employed when making this identification, and the accommodations and supports provided. Even with sup-ports and accommodations, respondents estimated that fewer than 25% of such students are able to succeed at the postsecondary level, although a larger per-centage appear to benefit from specialized college programs. Best practice guidelines are needed with respect to assessment and diagnosis of this condition, and specialized programs may be required to address success and retention at the postsecondary level

Medically confirmed functional impairment as proof of accommodation need in postsecondary education: Are Ontario’s campuses the bellwether of an inequitable decision-making paradigm?

Historically, students with disabilities in Canada provided comprehensive and objective documentation of their diagnosis and related functional impairments to access appropriate accommodations at the postsecondary level. Recently, some Canadian provinces have adopted an approach whereby students with mental health disabilities need not reveal their diagnosis; a healthcare professional may simply verify that a disability exists, enumerate the functional impairments, and detail the accommodations to be provided.   Without transparent documentation, Disability Services Offices frequently rely upon physicians for this information. We completed a census of all medical training programs in Ontario to evaluate the extent to which medical professionals receive training in determining functional impairments in postsecondary students with mental health conditions. Our findings demonstrated that the vast majority of medical residents receive no such training. Two programs report offering limited training in subjective methods such as self-report or the wishes of the client. Implications and recommended best practice are discussed

Educational Intervention to Increase Confidence and Knowledge of Pediatric Nurses Caring for Pediatric Mental Health Patients

Background: Given the rise in the mental health crisis, there is an increase of non-psychiatric nurses caring for pediatric mental health patients. This crisis leads nurses to experience feelings of doubt, hopelessness, stress, and insecurities in caring for this population. These feelings, combined with a lack of support and training, create a powerlessness loop of care. Local problem: In a Pediatric ICU, there is a lack of training and resources available to the nurses caring for pediatric mental health patients. Despite the lack of training, 35% of total admissions in 2020 were pediatric patients experiencing an acute mental health crisis. This patient population has been continually identified as an area of significant burnout, identified need, and frustration. Methods: Educational modules were assigned and included training on behavioral health communication, crisis management skills, therapeutic communication, assessment skills, mental health diagnoses, and psychotropic medications. A modified Behavioral Health Care Competency Tool was used to measure nurses’ confidence and knowledge at three timepoints. Results: There was a statistically significant improvement in nurses’ confidence and knowledge caring for mental health patients from pre- to post-intervention (M = 0.87, 95% CI [0.57, 1.160], p \u3c .001) and pre-intervention to one-month post-intervention (M = 1.11, 95% CI [0.71, 1.51], p \u3c .00). Conclusions: Providing educational training to nurses aids in increasing their confidence and knowledge in caring for mental health patients in non-psychiatric settings. Despite increases in confidence and knowledge, future implications include the need for pediatric-focused education, resources, and practice

Novel relationships among DNA methylation, histone modifications and gene expression in Ascobulus

By studying Ascobolus strains methylated in various portions of the native met2 gene or of the hph transgene, we generalized our previous observation that methylation of the downstream portion of a gene promotes its stable silencing and triggers the production of truncated transcripts which rarely extend through the methylated region. In contrast, methylation of the promoter region does not promote efficient gene silencing. The chromatin state of met2 methylated strains was investigated after partial micrococcal nuclease (MNase) digestion. We show that MNase sensitive sites present along the unmethylated regions are no longer observed along the methylated ones. These chromatin changes are not due to the absence of transcription. They are associated, in both met2 and hph, with modifications of core histones corresponding, on the N terminus of histone H3, to an increase of dimethylation of lysine 9 and a decrease of dimethylation of lysine 4. Contrary to other organisms, these changes are independent of the transcriptional state of the genes, and furthermore, no decrease in acetylation of histone H4 is observed in silenced genes

Checkpoint-Dependent and -Independent Roles of Swi3 in Replication Fork Recovery and Sister Chromatid Cohesion in Fission Yeast

Multiple genome maintenance processes are coordinated at the replication fork to preserve genomic integrity. How eukaryotic cells accomplish such a coordination is unknown. Swi1 and Swi3 form the replication fork protection complex and are involved in various processes including stabilization of replication forks, activation of the Cds1 checkpoint kinase and establishment of sister chromatid cohesion in fission yeast. However, the mechanisms by which the Swi1–Swi3 complex achieves and coordinates these tasks are not well understood. Here, we describe the identification of separation-of-function mutants of Swi3, aimed at dissecting the molecular pathways that require Swi1–Swi3. Unlike swi3 deletion mutants, the separation-of-function mutants were not sensitive to agents that stall replication forks. However, they were highly sensitive to camptothecin that induces replication fork breakage. In addition, these mutants were defective in replication fork regeneration and sister chromatid cohesion. Interestingly, unlike swi3-deleted cell, the separation-of-functions mutants were proficient in the activation of the replication checkpoint, but their fork regeneration defects were more severe than those of checkpoint mutants including cds1Δ, chk1Δ and rad3Δ. These results suggest that, while Swi3 mediates full activation of the replication checkpoint in response to stalled replication forks, Swi3 activates a checkpoint-independent pathway to facilitate recovery of collapsed replication forks and the establishment of sister chromatid cohesion. Thus, our separation-of-function alleles provide new insight into understanding the multiple roles of Swi1-Swi3 in fork protection during DNA replication, and into understanding how replication forks are maintained in response to different genotoxic agents

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Background: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. Methods: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. Findings: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. Funding: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research