A 3-D PYRAMID/PRISM APPROACH TO VIEW KNOWLEDGE REQUIREMENTS FOR THE BATCH MEANS METHOD WHEN TAUGHT IN A LANGUAGE-FOCUSED, UNDERGRADUATE SIMULATION COURSE

We develop a 3-D knowledge pyramid/prism model to structure the relationships of (i) lower-level learning, (ii) ‘optional ’ knowledge bases, (iii) concurrent knowledge, and (ii) new knowledge; so one may view the learning needs of a higher-level learning objective. Our paradigm stems from Bloom’s taxonomy of learning, but has the advantage of supporting ‘just-in-time ’ and ‘learn-by-doing’ delivery, teaching and learning styles. We illustrate the paradigm through the BMMKP (the 3-D knowledge pyramid/prism model of the highest-level, batch-means-method learning objective for our language-focused, undergraduate course). The BMMKP reveals how highly dependent and fully integrated this learning is to calculus, probability, statistics, and queuing theory—regardless of the simulation modeling language chosen to teach in the course. The BMMKP is then used to develop a set of lower-level learning objectives for the undergraduate course. The 3-D pyramid/prism approach should lend itself well as a communication tool for visualizing other simulation learning objectives.

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2

Background Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. Methods We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September–27 September 2021) and 15 (19 October–5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month. Results We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8–23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. Conclusions As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Nudging Discharge Readiness With a Poster: A Sequential, Exploratory Mixed Methods Pilot Study of Patient Caregivers

Many hospitals face a common challenge: limited space for a high number of patients. This has led to quick patient throughput, which can impact patient perception of discharge readiness. This study examined whether a poster highlighting tasks to complete as part of the discharge process improved caregiver perception of readiness to transition home. Using a sequential, exploratory mixed methods design, focus groups were convened to explore clinical staff perspective on the discharge process on 3 pediatric inpatient units at a large, urban, pediatric academic medical center in the United States. Analysis of this content informed the design of a poster intervention to “nudge” caregivers (eg, parents, legal guardians) toward readiness and self-efficacy that was then tested in a randomized, controlled experiment. The poster focused on practical knowledge for specific areas of transition adjustment, such as medication and care recipient recovery behaviors, barriers, and enablers. Caregivers (n = 135) completed surveys at discharge indicating their perceived readiness to transition home with their child. Analysis of covariance was used to test the effect of the poster condition (poster vs no poster) on caregiver readiness, preparedness, and confidence for discharge while controlling for previous admission history. Significant effects for poster presence were found on caregivers’ perceived readiness for discharge, F 1,125 = 7.75, P = .006, Cohen’s d = 0.44; and caregivers’ perceived preparedness for the transition home, F 1,121 =7.24, P = .008, Cohen’s d = 0.44. Only a marginal effect was found for poster condition on caregivers’ confidence ratings, F 1,125 = 2.93, P = .090, Cohen’s d = 0.29. The results suggest that simple nudges in the patient care environment may yield measurable improvements in caregiver outcomes. </jats:p

Nature Immunology / Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment

Cutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (TH2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II+ fibroblasts and dendritic cells that can maintain TH2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL