COVID-19 cluster surveillance using exposure data collected from routine contact tracing: The genomic validation of a novel informatics-based approach to outbreak detection in England.

Contact tracing was used globally to prevent onwards transmission of COVID-19. Tracing contacts alone is unlikely to be sufficient in controlling community transmission, due to the pre-symptomatic, overdispersed and airborne nature of COVID-19 transmission. We describe and demonstrate the validity of a national enhanced contact tracing programme for COVID-19 cluster surveillance in England. Data on cases occurring between October 2020 and September 2021 were extracted from the national contact tracing system. Exposure clusters were identified algorithmically by matching ≥2 cases attending the same event, identified by matching postcode and event category within a 7-day rolling window. Genetic validity was defined as exposure clusters with ≥2 cases from different households with identical viral sequences. Exposure clusters were fuzzy matched to the national incident management system (HPZone) by postcode and setting description. Multivariable logistic regression modelling was used to determine cluster characteristics associated with genetic validity. Over a quarter of a million (269,470) exposure clusters were identified. Of the eligible clusters, 25% (3,306/13,008) were genetically valid. 81% (2684/3306) of these were not recorded on HPZone and were identified on average of one day earlier than incidents recorded on HPZone. Multivariable analysis demonstrated that exposure clusters occurring in workplaces (aOR = 5·10, 95% CI 4·23-6·17) and education (aOR = 3·72, 95% CI 3·08-4·49) settings were those most strongly associated with genetic validity. Cluster surveillance using enhanced contact tracing in England was a timely, comprehensive and systematic approach to the detection of transmission events occurring in community settings. Cluster surveillance can provide intelligence to stakeholders to support the assessment and management of clusters of COVID-19 at a local, regional, and national level. Future systems should include predictive modelling and network analysis to support risk assessment of exposure clusters to improve the effectiveness of enhanced contract tracing for outbreak detection.

T-wave morphology abnormalities in the STREAM stage 1 trial.

BACKGROUND: Shorter regimens for drug-resistant tuberculosis (DR-TB) have non-inferior efficacy compared with longer regimens, but QT prolongation is a concern. T-wave morphology abnormalities may be a predictor of QT prolongation. RESEARCH DESIGN AND METHODS: STREAM Stage 1 was a randomized controlled trial in rifampicin-resistant TB, comparing short and long regimens. All participants had regular ECGs. QT/QTcF prolongation (≥500 ms or increase in ≥60 ms from baseline) was more common on the short regimen which contained high-dose moxifloxacin and clofazimine. Blinded ECGs were selected from the baseline, early (weeks 1-4), and late (weeks 12-36) time points. T-wave morphology was categorized as normal or abnormal (notched, asymmetric, flat-wave, flat peak, or broad). Differences between groups were assessed using Chi-Square tests (paired/unpaired, as appropriate). RESULTS: Two-hundred participants with available ECGs at relevant times were analyzed (QT prolongation group n = 82; non-prolongation group n = 118). At baseline, 23% (45/200) of participants displayed abnormal T-waves, increasing to 45% (90/200, p < 0.001) at the late time point. Abnormalities were more common in participants allocated the Short regimen (75/117, 64%) than the Long (14/38, 36.8%, p = 0.003); these occurred prior to QT/QTcF ≥500 ms in 53% of the participants (Long 2/5; Short 14/25). CONCLUSIONS: T-wave abnormalities may help identify patients at risk of QT prolongation on DR-TB treatment. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02409290). Current Controlled Trial number, ISRCTN78372190.

An octameric PqiC toroid stabilises the outer-membrane interaction of the PqiABC transport system.

The E. coli Paraquat Inducible (Pqi) Pathway is a putative Gram-negative phospholipid transport system. The pathway comprises three components: an integral inner membrane protein (PqiA), a periplasmic spanning MCE family protein (PqiB) and an outer membrane lipoprotein (PqiC). Interactions between all complex components, including stoichiometry, remain uncharacterised; nevertheless, once assembled into their quaternary complex, the trio of Pqi proteins are anticipated to provide a continuous channel between the inner and outer membranes of diderms. Here, we present X-ray structures of both the native and a truncated, soluble construct of the PqiC lipoprotein, providing insight into its biological assembly, and utilise neutron reflectometry to characterise the nature of the PqiB-PqiC-membrane interaction. Finally, we employ phenotypic complementation assays to probe specific PqiC residues, which imply the interaction between PqiB and PqiC is less intimate than previously anticipated.

A Bayesian multivariate factor analysis model for causal inference using time-series observational data on mixed outcomes.

Assessing the impact of an intervention by using time-series observational data on multiple units and outcomes is a frequent problem in many fields of scientific research. Here, we propose a novel Bayesian multivariate factor analysis model for estimating intervention effects in such settings and develop an efficient Markov chain Monte Carlo algorithm to sample from the high-dimensional and nontractable posterior of interest. The proposed method is one of the few that can simultaneously deal with outcomes of mixed type (continuous, binomial, count), increase efficiency in the estimates of the causal effects by jointly modeling multiple outcomes affected by the intervention, and easily provide uncertainty quantification for all causal estimands of interest. Using the proposed approach, we evaluate the impact that Local Tracing Partnerships had on the effectiveness of England's Test and Trace programme for COVID-19.

Evaluating the impact on health outcomes of an event that resulted in a delay in contact tracing of COVID-19 cases in England, September 2020: an observational study.

OBJECTIVE: In September 2020, 15 861 SARS-CoV-2 case records failed to upload from the Second Generation Surveillance System (SGSS) to the Contact Tracing Advisory Service (CTAS) tool, delaying the contact tracing of these cases. This study used CTAS data to determine the impact of this delay on population health outcomes: transmission events, hospitalisations and mortality. Previously, a modelling study suggested a substantial impact. DESIGN: Observational study. SETTING: England. POPULATION: Individuals testing positive for SARS-CoV-2 and their reported contacts. MAIN OUTCOME MEASURES: Secondary attack rates (SARs), hospitalisations and deaths among primary and secondary contacts were calculated, compared with all other concurrent, unaffected cases. Affected SGSS records were matched to CTAS records. Successive contacts and cases were identified and matched to hospital episode and mortality outcomes. RESULTS: Initiation of contact tracing was delayed by 3 days on average in the primary cases in the delay group (6 days) compared with the control group (3 days). This was associated with lower completion of contact tracing: 80% (95% CI: 79% to 81%) in delay group and 83% (95% CI: 83% to 84%) in control group. There was some evidence to suggest increased transmission to non-household contacts among those affected by the delay. The SAR for non-household contacts was higher among secondary contacts in the delay group than the control group (delay group: 7.9%, 95% CI: 6.5% to 9.2%; control group: 5.9%, 95% CI: 5.3% to 6.6%). There did not appear to be a significant difference between the delay and control groups in the odds of hospitalisation (crude OR: 1.1 (95% CI: 0.9 to 1.2)) or death (crude OR: 0.7 (95% CI: 0.1 to 4.0)) among secondary contacts. CONCLUSIONS: Our analysis suggests that the delay in contact tracing had a limited impact on population health outcomes; however, contact tracing was not completed for all individuals, so some transmission events might not be captured.

Delivering manual cardiopulmonary resuscitation (CPR) in a diving bell: an analysis of head-to-chest and knee-to-chest compression techniques.

Introduction: Chest compression often cannot be administered using conventional techniques in a diving bell. Multiple alternative techniques are taught, including head-to-chest and both prone and seated knee-to-chest compressions, but there are no supporting efficacy data. This study evaluated the efficacy, safety and sustainability of these techniques. Methods: Chest compressions were delivered by a team of expert cardiopulmonary resuscitation (CPR) providers. The primary outcome was proportion of chest compressions delivered to target depth compared to conventional CPR. Techniques found to be safe and potentially effective by the study team were further trialled by 20 emergency department staff members. Results: Expert providers delivered a median of 98% (interquartile range [IQR] 1.5%) of chest compressions to the target depth using conventional CPR. Only 32% (IQR 60.8%) of head-to-chest compressions were delivered to depth; evaluation of the technique was abandoned due to adverse effects. No study team member could register sustained compression outputs using prone knee-to-chest compressions. Seated knee-to-chest were delivered to depth 12% (IQR 49%) of the time; some compression providers delivered > 90% of compressions to depth. Conclusions: Head-to-chest compressions have limited efficacy and cause harm to providers; they should not be taught or used. Prone knee-to-chest compressions are ineffective. Seated knee-to-chest compressions have poor overall efficacy but some providers deliver them well. Further research is required to establish whether this technique is feasible, effective and sustainable in a diving bell setting, and whether it can be taught and improved with practise.

An evaluation of the NUI Compact Chest Compression Device (NCCD), a mechanical CPR device suitable for use in the saturation diving environment.

Introduction: Provision of manual chest compressions in a diving bell using a conventional technique is often impossible, and alternative techniques are poorly evidenced in terms of efficacy and sustainability. The first mechanical cardiopulmonary resuscitation (CPR) device suitable for use in this environment, the NUI Compact Chest Compression Device (NCCD), has recently been designed and manufactured. This study assessed both the efficacy of the device in delivering chest compressions to both prone and seated manikins, and the ability of novice users to apply and operate it. Methods: Compression efficacy was assessed using a Resusi Anne QCPR intelligent manikin, and the primary outcome was the proportion of compressions delivered to target depth (50-60 mm). The gold standard was that achieved by expert CPR providers delivering manual CPR; the LUCAS 3 mCPR device was a further comparator. Results: The NCCD delivered 100% of compressions to target depth compared to 98% for the gold standard (interquartile range 1.5%) and 98% for the LUCAS 3 when applied to both supine and seated manikins. The NCCD sometimes became dislodged and had to be reapplied when used with a seated manikin. Conclusions: The NCCD can deliver chest compressions at target rate and depth to both supine and seated manikins with efficacy equivalent to manual CPR and the LUCAS 3. It can become dislodged when applied to a seated manikin; its design has now been altered to prevent this. New users can be trained in use of the NCCD quickly, but practise is required to ensure effective use.

Drugless and radiographer led: the start of a new era for CT coronary angiography.

OBJECTIVE: Since inception CT coronary angiography (CTCA) has required facilitating beta blockers (BB). However, CT technology has improved rapidly as has radiographer and reporter expertise. Using these factors, we instituted a radiographer led cardiac CT service (RLCCTS), without routine BB, which we studied for quality control (QC). METHODS: RLCCTS started October 2021 using a wide detector array CT system, with 20 min slots. QC study was registered with the clinical audit team, University Hospitals Plymouth, CA_2020-21-118. Uniform reporting was agreed including indication, BB administration, demographics, dose length product (DLP) and the coronary artery disease-reporting and data system (CAD-RADS) score. Uncertain CAD-RADS meant a non-diagnostic scan (NDS). Six months of data were collected; stable chest pain (SCP) patients, who have national CTCA QC comparators, were analysed using descriptive statistics. RESULTS: Of 1475 patients, 447 were not SCP patients-known CAD (157); valves (286); removed (4, data incomplete) leaving 1028 SCP patients CTCA for analysis. Demographics-mean age 63 years, body mass index 29, 50.4% women. BB therapy-four patients (two recalls). Overall, 36/1024 or 3.5% were NDS; median DLP 173mGy×cm; mean heart rate (HR) 70 bpm, 99/1024 or 9.7% HR >90 bpm (45% not sinus rhythm). CONCLUSIONS: Quality for RLCCTS was judged by NDS rate and DLP. National QC comparators suggest 4% NDS rate; median DLP for SCPP CTCA 209 mGy×cm. RLCCTS compares favourably. With modern cardiac CT, experienced radiographers and reporters, 'drugless' RLCCTS can deliver 20 min slot CTCA with satisfactory QC indicators.

Comparative transmission of SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants and the impact of vaccination: national cohort study, England.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) rapidly replaced Delta (B.1.617.2) to become dominant in England. Our study assessed differences in transmission between Omicron and Delta using two independent data sources and methods. Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for named contacts were calculated in household and non-household settings using contact tracing data, while household clustering was identified using national surveillance data. Logistic regression models were applied to control for factors associated with transmission for both methods. For contact tracing data, higher secondary attack rates for Omicron vs. Delta were identified in households (15.0% vs. 10.8%) and non-households (8.2% vs. 3.7%). For both variants, in household settings, onward transmission was reduced from cases and named contacts who had three doses of vaccine compared to two, but this effect was less pronounced for Omicron (adjusted risk ratio, aRR 0.78 and 0.88) than Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed only in contacts who had three doses vs. two doses for both Delta (aRR 0.51) and Omicron (aRR 0.76). For national surveillance data, the risk of household clustering, was increased 3.5-fold for Omicron compared to Delta (aRR 3.54 (3.29-3.81)). Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.

Feasibility and evaluation of an emergency department-based general practitioner streaming and treatment service.

RATIONALE: Offering a primary care service that can provide good quality primary care at emergency departments may reduce pressure on usual emergency department (ED) services. AIMS AND OBJECTIVES: To evaluate the acceptability, satisfaction, and potential impacts of a co-located primary care service at an emergency department. METHODS: This is a prospective feasibility study and service evaluation comprising a narrative summary of activity, satisfaction, well-being, and safety, and comparisons of wait times for ED services by patient category ('minor', 'majors', 'paediatric' or 'resus') before and during the service operation. Patients and staff were asked using semistructured interview topic guides about service perception, well-being, representation within 48 h, safety concerns, and/or satisfaction. Wait times for patient categories in usual ED care service were in secondary care electronic records. Pathway changes were captured under primary care electronic records. RESULTS: Approximately 96% of general practitioner streaming and treatment (GPST) patients were seen within 1 h. There was a statistically significant reduction in ED patients with minor injuries or illnesses waiting >4 h for admission or discharge 'breaches' during the 3 months that GPST was operating compared with the previous 3 months (p ≤ 0.005). Wait times for other ED services did not significantly improve. A total of 769 walk-in patients received GPST consultation and 661 (86%) needed no further ED intervention. Fast discharge was a major determinant of patient satisfaction. No staff expressed dissatisfaction, but some suggested possible improvements in eligibility criteria and built environment design features. CONCLUSION: Provision of GPST correlated with shorter waits for discharge from ED. Patient and staff experiences of GPST were positive.

Discovery of Clinical Candidate AZD0095, a Selective Inhibitor of Monocarboxylate Transporter 4 (MCT4) for Oncology.

Due to increased reliance on glycolysis, which produces lactate, monocarboxylate transporters (MCTs) are often upregulated in cancer. MCT4 is associated with the export of lactic acid from cancer cells under hypoxia, so inhibition of MCT4 may lead to cytotoxic levels of intracellular lactate. In addition, tumor-derived lactate is known to be immunosuppressive, so MCT4 inhibition may be of interest for immuno-oncology. At the outset, no potent and selective MCT4 inhibitors had been reported, but a screen identified a triazolopyrimidine hit, with no close structural analogues. Minor modifications to the triazolopyrimidine were made, alongside design of a constrained linker and broad SAR exploration of the biaryl tail to improve potency, physical properties, PK, and hERG. The resulting clinical candidate 15 (AZD0095) has excellent potency (1.3 nM), MCT1 selectivity (>1000×), secondary pharmacology, clean mechanism of action, suitable properties for oral administration in the clinic, and good preclinical efficacy in combination with cediranib.

The ESCAPE Open-source Software and Service Repository.

Purpose: The purpose of the ESCAPE Open-source Software and Service Repository (OSSR) is to provide a central location for the dissemination and use of trusted open-source software in the fields of astronomy, astroparticle physics, and particle physics. The repository allows users to easily access and download tools and services developed within the community, and to contribute their own tools and services. Methods: The ESCAPE project has set up a curated repository of software that provides tools and an environment to make it easy for users to find and download the software and services that they need. The repository is regularly updated and is maintained by a curation board, ensuring that the software and services are reliable and up-to-date. The curation and onboarding process makes the OSSR a trustworthy source of software that can be used for scientific analysis. The software included in the repository must include documentation and instructions and follow a set of modern best practices in software development. Training is provided to students and researchers to help them provide high-quality scientific software following modern software development practices. Outcome: The OSSR currently contains a wide range of software and services, including those for data management, data analysis, and machine learning. These tools and services are used by researchers and other users around the world. The OSSR has proven to be an effective means for disseminating and providing open-source software and services developed by the ESCAPE project partners and welcomes contributions from the entire community.

The ESCAPE (European Science Cluster of Astronomy & Particle physics ESFRI research infrastructures) Open-source Software and Service Repository (OSSR) is a place where scientists can find and download software and services they need for their work in astronomy, astroparticle physics, and particle physics. This repository is updated regularly and maintained by a group of experts to make sure that the software is reliable and open-source to maximize its reuse. The software available on the repository must come with instructions and follow good software development practices. The OSSR provides training to students, researchers, and software developers to help them create high-quality software. The OSSR includes a variety of tools and services for things like data management and analysis that are used by researchers worldwide.

Understanding how the university curriculum impacts student wellbeing: a qualitative study.

There is increasing pressure within universities to address student mental health. From a whole university or settings-based perspective, this could include curriculum-embedded approaches. There is little research about how this should work or what approaches might be most effective. Semi -structured interviews were conducted with fifty-seven undergraduate students from five disciplines (Psychology, English studies, Nursing, International Politics, and War Studies) to understand students' perspectives. Students reflected on wellbeing module content and, more broadly, on curriculum processes (teaching, pedagogy, assessment) within their degree. Reflexive thematic analysis was applied to transcripts, generating three themes: embedding wellbeing in the curriculum; assessment, challenge, and academic support; and social connection and interaction. The findings provide evidence for teaching, pedagogy, and assessment practices supporting higher education student wellbeing. These align with recommended good teaching practices, such as considering appropriate assessment methods followed by effective feedback. Students saw the benefits of being academically challenged if scaffolded appropriately. Strong peer connection, teacher-student interaction, and communication were crucial to learning and wellbeing. These findings provide implications for future curriculum design that can support learning and wellbeing.

Real-world clinical effectiveness and sustainability of universal bloodborne virus testing in an urban emergency department in the UK.

Innovative testing approaches and care pathways are required to meet HIV, hepatitis B (HBV) and hepatitis C (HCV) elimination goals. Routine testing for blood-borne viruses (BBVs) within emergency departments (EDs) is suggested by the European Centre for Disease Prevention and Control but there is a paucity of supporting evidence. We evaluated the introduction of routine BBV testing in EDs at a large teaching hospital in northern England. In October 2018, we modified the electronic laboratory ordering system to reflex opt-out HIV, HBV and HCV testing for all ED attendees aged 16-65 years who had a routine blood test for urea and electrolytes (U&Es). Linkage to care (LTC) was attempted for newly diagnosed patients, those never referred and those who had previously disengaged from care. The project operated for 18 months, here we present evaluation of the initial nine months (2 October 2018-1 July 2019). We analysed testing uptake, BBV seropositivity, LTC and treatment initiation within six months post-diagnosis. Over 9 months, 17,026/28,178 (60.4%) ED attendees who had U&Es performed were tested for ≥ 1 BBV. 299 active BBV infections were identified: 70 HIV Ab/Ag-positive (0.4% seroprevalence), 73 HBsAg-positive (0.4%) and 156 HCV RNA-positive (1.0%). Only 24.3% (17/70) HIV Ab/Ag-positive individuals required LTC, compared to 94.9% (148/156) HCV RNA-positive and 53.4% (39/73) HBsAg-positive individuals. LTC was successful in 94.1% (16/17) HIV Ab/Ag-positive and 69.3% (27/39) HBsAg-positive individuals. However, at 6 months LTC was just 39.2% (58/148) for HCV RNA-positive individuals, with 64% (37/58) of these commencing treatment. Universal opt-out ED BBV testing proved feasible and effective in identifying active BBV infections, especially among marginalised populations with reduced healthcare access. Our integrated approach achieved good LTC rates although further service development is necessary, particularly for HCV RNA-positive people who inject drugs.

ATM Regulates Differentiation of Myofibroblastic Cancer-Associated Fibroblasts and Can Be Targeted to Overcome Immunotherapy Resistance.

Myofibroblastic cancer-associated fibroblast (myoCAF)-rich tumors generally contain few T cells and respond poorly to immune-checkpoint blockade. Although myoCAFs are associated with poor outcome in most solid tumors, the molecular mechanisms regulating myoCAF accumulation remain unclear, limiting the potential for therapeutic intervention. Here, we identify ataxia-telangiectasia mutated (ATM) as a central regulator of the myoCAF phenotype. Differentiating myofibroblasts in vitro and myoCAFs cultured ex vivo display activated ATM signaling, and targeting ATM genetically or pharmacologically could suppress and reverse differentiation. ATM activation was regulated by the reactive oxygen species-producing enzyme NOX4, both through DNA damage and increased oxidative stress. Targeting fibroblast ATM in vivo suppressed myoCAF-rich tumor growth, promoted intratumoral CD8 T-cell infiltration, and potentiated the response to anti-PD-1 blockade and antitumor vaccination. This work identifies a novel pathway regulating myoCAF differentiation and provides a rationale for using ATM inhibitors to overcome CAF-mediated immunotherapy resistance. SIGNIFICANCE: ATM signaling supports the differentiation of myoCAFs to suppress T-cell infiltration and antitumor immunity, supporting the potential clinical use of ATM inhibitors in combination with checkpoint inhibition in myoCAF-rich, immune-cold tumors.

ATM kinase inhibitor AZD0156 in combination with irinotecan and 5-fluorouracil in preclinical models of colorectal cancer.

BACKGROUND: AZD0156 is an oral inhibitor of ATM, a serine threonine kinase that plays a key role in DNA damage response (DDR) associated with double-strand breaks. Topoisomerase-I inhibitor irinotecan is used clinically to treat colorectal cancer (CRC), often in combination with 5-fluorouracil (5FU). AZD0156 in combination with irinotecan and 5FU was evaluated in preclinical models of CRC to determine whether low doses of AZD0156 enhance the cytotoxicity of irinotecan in chemotherapy regimens used in the clinic. METHODS: Anti-proliferative effects of single-agent AZD0156, the active metabolite of irinotecan (SN38), and combination therapy were evaluated in 12 CRC cell lines. Additional assessment with clonogenic assay, cell cycle analysis, and immunoblotting were performed in 4 selected cell lines. Four colorectal cancer patient derived xenograft (PDX) models were treated with AZD0156, irinotecan, or 5FU alone and in combination for assessment of tumor growth inhibition (TGI). Immunofluorescence was performed on tumor tissues. The DDR mutation profile was compared across in vitro and in vivo models. RESULTS: Enhanced effects on cellular proliferation and regrowth were observed with the combination of AZD0156 and SN38 in select models. In cell cycle analysis of these models, increased G2/M arrest was observed with combination treatment over either single agent. Immunoblotting results suggest an increase in DDR associated with irinotecan therapy, with a reduced effect noted when combined with AZD0156, which is more pronounced in some models. Increased TGI was observed with the combination of AZD0156 and irinotecan as compared to single-agent therapy in some PDX models. The DDR mutation profile was variable across models. CONCLUSIONS: AZD0156 and irinotecan provide a rational and active combination in preclinical colorectal cancer models. Variability across in vivo and in vitro results may be related to the variable DDR mutation profiles of the models evaluated. Further understanding of the implications of individual DDR mutation profiles may help better identify patients more likely to benefit from treatment with the combination of AZD0156 and irinotecan in the clinical setting.

Radiologist opinions regarding reporting incidental coronary and cardiac calcification on thoracic CT.

Objectives: Coronary and cardiac calcification are frequent incidental findings on non-gated thoracic computed tomography (CT). However, radiologist opinions and practices regarding the reporting of incidental calcification are poorly understood. Methods: UK radiologists were invited to complete this online survey, organised by the British Society of Cardiovascular Imaging (BSCI). Questions included anonymous information on subspecialty, level of training and reporting practices for incidental coronary artery, aortic valve, mitral and thoracic aorta calcification. Results: The survey was completed by 200 respondents: 10% trainees and 90% consultants. Calcification was not reported by 11% for the coronary arteries, 22% for the aortic valve, 35% for the mitral valve and 37% for the thoracic aorta. Those who did not subspecialise in cardiac imaging were less likely to report coronary artery calcification (p = 0.005), aortic valve calcification (p = 0.001) or mitral valve calcification (p = 0.008), but there was no difference in the reporting of thoracic aorta calcification. Those who did not subspecialise in cardiac imaging were also less likely to provide management recommendations for coronary artery calcification (p < 0.001) or recommend echocardiography for aortic valve calcification (p < 0.001), but there was no difference for mitral valve or thoracic aorta recommendations. Conclusion: Incidental coronary artery, valvular and aorta calcification are frequently not reported on thoracic CT and there are differences in reporting practices based on subspeciality. Advances in knowledge: On routine thoracic CT, 11% of radiologists do not report coronary artery calcification. Radiologist reporting practices vary depending on subspeciality but not level of training.

Comparative symptomatology of infection with SARS-CoV-2 variants Omicron (B.1.1.529) and Delta (B.1.617.2) from routine contact tracing data in England.

Symptoms are currently used as testing indicators for SARS-CoV-2 in England. In this study, we analysed national contact tracing data for England (NHS Test and Trace) for the period 1 December to 28 December 2021 to explore symptom differences between the variants, Delta and Omicron. We found that at least one of the symptoms currently used as indicators (fever, cough and loss of smell and taste) were reported in 61.5% of Omicron cases and 72.2% in Delta cases, suggesting that these symptoms are less predictive of Omicron infections. Nearly 40% of Omicron infections did not report any of the three key indicative symptoms, reinforcing the importance of the entire spectrum of symptoms for targeted testing. After adjusting for potential confounding factors, fever and cough were more commonly associated with Omicron infections compared to Delta, showing the importance of considering age and vaccination status when assessing symptom profiles. Sore throat was also more commonly reported in Omicron infections, and loss of smell and taste more commonly reported in Delta infections. Our study shows the value of continued monitoring of symptoms associated with SARS-CoV-2, as changes may influence the effectiveness of testing policy and case ascertainment approaches.

The impact of clinical simulation on the development of advanced practice skills.

This article considers the findings of a qualitative research study into the impact of simulation on the development of advanced clinical practitioners' skills and knowledge. STUDY AIM: To explore simulated learning through the eyes of trainee and trained advanced clinical practitioners (ACPs) and consider its potential in supporting their development. METHOD: This qualitative research study explored the experiences of trained and trainee ACP volunteers undertaking a structured simulated event provided by a local acute hospital trust simulation team. A questionnaire (n=10) and a focus group (n=4) acted as the data gathering tools. RESULTS: Although simulation can be daunting for the participants, the overwhelming outcome was positive. Participants stated that they gained confidence and suggested that simulation offered a safe place to practise the challenging scenarios that occur in the clinical environment. Additionally, they emphasised that simulation provided a place to network and receive constructive feedback that was non-judgemental, and which helped them to develop clinical knowledge and appreciate their limitations. CONCLUSION: Simulation is a valuable addition to the education and development of ACPs. It should be considered for inclusion within the educational curriculum as a supplement to theoretical knowledge and to the structured clinical supervision provided within the clinical environment.