The Epstein-Barr Virus Episome Maneuvers between Nuclear Chromatin Compartments during Reactivation.

The human genome is structurally organized in three-dimensional space to facilitate functional partitioning of transcription. We learned that the latent episome of the human Epstein-Barr virus (EBV) preferentially associates with gene-poor chromosomes and avoids gene-rich chromosomes. Kaposi's sarcoma-associated herpesvirus behaves similarly, but human papillomavirus does not. Contacts on the EBV side localize to OriP, the latent origin of replication. This genetic element and the EBNA1 protein that binds there are sufficient to reconstitute chromosome association preferences of the entire episome. Contacts on the human side localize to gene-poor and AT-rich regions of chromatin distant from transcription start sites. Upon reactivation from latency, however, the episome moves away from repressive heterochromatin and toward active euchromatin. Our work adds three-dimensional relocalization to the molecular events that occur during reactivation. Involvement of myriad interchromosomal associations also suggests a role for this type of long-range association in gene regulation.IMPORTANCE The human genome is structurally organized in three-dimensional space, and this structure functionally affects transcriptional activity. We set out to investigate whether a double-stranded DNA virus, Epstein-Barr virus (EBV), uses mechanisms similar to those of the human genome to regulate transcription. We found that the EBV genome associates with repressive compartments of the nucleus during latency and with active compartments during reactivation. This study advances our knowledge of the EBV life cycle, adding three-dimensional relocalization as a novel component to the molecular events that occur during reactivation. Furthermore, the data add to our understanding of nuclear compartments, showing that disperse interchromosomal interactions may be important for regulating transcription

PhylOTU: a high-throughput procedure quantifies microbial community diversity and resolves novel taxa from metagenomic data.

Microbial diversity is typically characterized by clustering ribosomal RNA (SSU-rRNA) sequences into operational taxonomic units (OTUs). Targeted sequencing of environmental SSU-rRNA markers via PCR may fail to detect OTUs due to biases in priming and amplification. Analysis of shotgun sequenced environmental DNA, known as metagenomics, avoids amplification bias but generates fragmentary, non-overlapping sequence reads that cannot be clustered by existing OTU-finding methods. To circumvent these limitations, we developed PhylOTU, a computational workflow that identifies OTUs from metagenomic SSU-rRNA sequence data through the use of phylogenetic principles and probabilistic sequence profiles. Using simulated metagenomic data, we quantified the accuracy with which PhylOTU clusters reads into OTUs. Comparisons of PCR and shotgun sequenced SSU-rRNA markers derived from the global open ocean revealed that while PCR libraries identify more OTUs per sequenced residue, metagenomic libraries recover a greater taxonomic diversity of OTUs. In addition, we discover novel species, genera and families in the metagenomic libraries, including OTUs from phyla missed by analysis of PCR sequences. Taken together, these results suggest that PhylOTU enables characterization of part of the biosphere currently hidden from PCR-based surveys of diversity

Sustainability Matters: Guiding Principles for Sustainability in Occupational Therapy Practice, Education and Scholarship

Introduction The environment (context of occupational performance) has always been a focus for occupational therapists. Recently, sustainability has become a key occupational therapy topic (Swedish Association of Occupational Therapists 2012, College of Occupational Therapists 2013). Following the World Federation of Occupational Therapists (2012) position statement on environmental sustainability, it is timely for WFOT to provide curricula guidelines in ‘Sustainability Matters: Guiding Principles on Sustainable Development’. This addresses the relevance of sustainable development to human occupational performance, making it part of occupational therapy’s professional scope. It follows a wider global awareness of sustainability amongst health professions and governmental organisations, and the recognition that “climate change is the biggest global health threat of the 21st century” (UCL-Lancet Commission 2009, p.1659) affecting all human populations

A perspective on life-cycle health technology assessment and real-world evidence for precision oncology in Canada

Health technology assessment (HTA) can be used to make healthcare systems more equitable and efficient. Advances in precision oncology are challenging conventional thinking about HTA. Precision oncology advances are rapid, involve small patient groups, and are frequently evaluated without a randomized comparison group. In light of these challenges, mechanisms to manage precision oncology uncertainties are critical. We propose a life-cycle HTA framework and outline supporting criteria to manage uncertainties based on real world data collected from learning healthcare systems. If appropriately designed, we argue that life-cycle HTA is the driver of real world evidence generation and furthers our understanding of comparative effectiveness and value. We conclude that life-cycle HTA deliberation processes must be embedded into healthcare systems for an agile response to the constantly changing landscape of precision oncology innovation. We encourage further research outlining the core requirements, infrastructure, and checklists needed to achieve the goal of learning healthcare supporting life-cycle HTA

Lithium diamidodihydridoaluminates : bimetallic cooperativity in catalytic hydroboration and metallation applications

Cooperativity between the Li and Al centres is implicated in catalytic hydroboration reactions of aldehydes and ketones with pinacolborane via heteroleptic lithium diamidodihydridoaluminates. In addition to implementing hydroalumination, these versatile heteroleptic ates can also perform as amido bases as illustrated with an acidic triazole

Injection fears and COVID-19 vaccine hesitancy.

BACKGROUND: When vaccination depends on injection, it is plausible that the blood-injection-injury cluster of fears may contribute to hesitancy. Our primary aim was to estimate in the UK adult population the proportion of COVID-19 vaccine hesitancy explained by blood-injection-injury fears. METHODS: In total, 15 014 UK adults, quota sampled to match the population for age, gender, ethnicity, income and region, took part (19 January-5 February 2021) in a non-probability online survey. The Oxford COVID-19 Vaccine Hesitancy Scale assessed intent to be vaccinated. Two scales (Specific Phobia Scale-blood-injection-injury phobia and Medical Fear Survey-injections and blood subscale) assessed blood-injection-injury fears. Four items from these scales were used to create a factor score specifically for injection fears. RESULTS: In total, 3927 (26.2%) screened positive for blood-injection-injury phobia. Individuals screening positive (22.0%) were more likely to report COVID-19 vaccine hesitancy compared to individuals screening negative (11.5%), odds ratio = 2.18, 95% confidence interval (CI) 1.97-2.40, p < 0.001. The population attributable fraction (PAF) indicated that if blood-injection-injury phobia were absent then this may prevent 11.5% of all instances of vaccine hesitancy, AF = 0.11; 95% CI 0.09-0.14, p < 0.001. COVID-19 vaccine hesitancy was associated with higher scores on the Specific Phobia Scale, r = 0.22, p < 0.001, Medical Fear Survey, r = 0.23, p = <0.001 and injection fears, r = 0.25, p < 0.001. Injection fears were higher in youth and in Black and Asian ethnic groups, and explained a small degree of why vaccine hesitancy is higher in these groups. CONCLUSIONS: Across the adult population, blood-injection-injury fears may explain approximately 10% of cases of COVID-19 vaccine hesitancy. Addressing such fears will likely improve the effectiveness of vaccination programmes

Neural G0:a quiescent-like state found in neuroepithelial-derived cells and glioma

Single‐cell RNA sequencing has emerged as a powerful tool for resolving cellular states associated with normal and maligned developmental processes. Here, we used scRNA‐seq to examine the cell cycle states of expanding human neural stem cells (hNSCs). From these data, we constructed a cell cycle classifier that identifies traditional cell cycle phases and a putative quiescent‐like state in neuroepithelial‐derived cell types during mammalian neurogenesis and in gliomas. The Neural G0 markers are enriched with quiescent NSC genes and other neurodevelopmental markers found in non‐dividing neural progenitors. Putative glioblastoma stem‐like cells were significantly enriched in the Neural G0 cell population. Neural G0 cell populations and gene expression are significantly associated with less aggressive tumors and extended patient survival for gliomas. Genetic screens to identify modulators of Neural G0 revealed that knockout of genes associated with the Hippo/Yap and p53 pathways diminished Neural G0 in vitro, resulting in faster G1 transit, down‐regulation of quiescence‐associated markers, and loss of Neural G0 gene expression. Thus, Neural G0 represents a dynamic quiescent‐like state found in neuroepithelial‐derived cells and gliomas

Identifying Child Anxiety Through Schools-identification to intervention (iCATS-i2i):protocol for a cluster randomised controlled trial to compare screening, feedback and intervention for child anxiety problems to usual school practice

Background: Systematically screening for child anxiety problems, and offering and delivering a brief, evidence-based intervention for children who are identified as likely to benefit would minimise common barriers that families experience in accessing treatment. We have developed a short parent-report child anxiety screening questionnaire, and procedures for administering screening questionnaires, sharing screening outcomes with families, and offering and delivering a brief parent-led online intervention (OSI: Online Support and Intervention for child anxiety) through schools. This trial aims to evaluate clinical and health economic outcomes for (1) children (aged 8–9) who screen positive for anxiety problems at baseline (target population) and (2) the wider population of all children in participating classes (total population) in schools randomly allocated to receive identification-to-intervention procedures and usual school practice (‘screening and intervention’), compared to assessment and usual school practice only (‘usual school practice’). Methods: The trial design is a parallel-group, superiority cluster randomised controlled trial, with schools (clusters) randomised to ‘screening and intervention’ or ‘usual school practice’ arms in a 1:1 ratio stratified according to the level of deprivation within the school. We will recruit schools and participants in two phases (a pilot phase (Phase 1) and Phase 2), with progression criteria assessed prior to progressing to Phase 2. In total, the trial will recruit 80 primary/junior schools in England, and 398 children (199 per arm) who screen positive for anxiety problems at baseline (target population). In schools allocated to ‘screening and intervention’: (1) parents/carers will complete a brief parent-report child anxiety screening questionnaire (at baseline) and receive feedback on their child’s screening outcomes (after randomisation), (2) classes will receive a lesson on managing fears and worries and staff will be provided with information about the intervention and (3) parents/carers of children who screen positive for anxiety problems (target population) will be offered OSI. OSI will also be available for any other parents/carers of children in participating classes (total population) who request it. We will collect child-, parent- and teacher-report measures for the target population and total population at baseline (before randomisation), 4 months, 12 months and 24 months post-randomisation. The primary outcome will be the proportion of children who screen positive for anxiety problems at baseline (target population) who screen negative for anxiety problems 12 months post-randomisation. Discussion: This trial will establish if systematic screening for child anxiety problems, sharing screening outcomes with families and delivering a brief parent-led online intervention through schools is effective and cost-effective. Trial registration: ISRCTN registry ISRCTN76119074. Prospectively registered on 4.1.2022.</p