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The pathogenesis of exercise intolerance and persistent fatigue which can follow an infection with the SARS‐CoV‐2 virus (“long COVID”) is not fully understood. Cases were recruited from a long COVID clinic (N = 32; 44 ± 12 years; 10 (31%) men), and age‐/sex‐matched healthy controls (HC) (N = 19; 40 ± 13 years; 6 (32%) men) from University College London staff and students. We assessed exercise performance, lung and cardiac function, vascular health, skeletal muscle oxidative capacity, and autonomic nervous system (ANS) function. Key outcome measures for each physiological system were compared between groups using potential outcome means (95% confidence intervals) adjusted for potential confounders. Long COVID participant outcomes were compared to normative values. When compared to HC, cases exhibited reduced oxygen uptake efficiency slope (1847 (1679, 2016) vs. 2176 (1978, 2373) mL/min, p = 0.002) and anaerobic threshold (13.2 (12.2, 14.3) vs. 15.6 (14.4, 17.2) mL/kg/min, p < 0.001), and lower oxidative capacity, measured using near infrared spectroscopy (τ: 38.7 (31.9, 45.6) vs. 24.6 (19.1, 30.1) s, p = 0.001). In cases, ANS measures fell below normal limits in 39%. Long COVID is associated with reduced measures of exercise performance and skeletal muscle oxidative capacity in the absence of evidence of microvascular dysfunction, suggesting mitochondrial pathology. There was evidence of attendant ANS dysregulation in a significant proportion. These multisystem factors might contribute to impaired exercise tolerance in long COVID sufferers.

PurposeThe pathogenesis of the long-lasting symptoms which can follow an infection with the SARS-CoV-2 virus (‘long covid’) is not fully understood. The ‘COroNaVirus post-Acute Long-term EffectS: Constructing an evidENCE base’ (CONVALESCENCE) study was established as part of the Longitudinal Health and Wellbeing COVID-19 UK National Core Study. We performed a deep phenotyping case-control study nested within two cohorts (the Avon Longitudinal Study of Parents and Children and TwinsUK) as part of CONVALESCENCE.ParticipantsFrom September 2021 to May 2023, 349 participants attended the CONVALESCENCE deep phenotyping clinic at University College London. Four categories of participants were recruited: cases of long covid (long covid(+)/SARS-CoV-2(+)), alongside three control groups: those with neither long covid symptoms nor evidence of prior COVID-19 (long covid(-)/SARS-CoV-2(-); control group 1), those who self-reported COVID-19 and had evidence of SARS-CoV-2 infection, but did not report long covid (long covid(-)/SARS-CoV-2(+); control group 2) and those who self-reported persistent symptoms attributable to COVID-19 but no evidence of SARS-CoV-2 infection (long covid(+)/SARS-CoV-2(-); control group 3). Remote wearable measurements were performed up until February 2024.Findings to dateThis cohort profile describes the baseline characteristics of the CONVALESCENCE cohort. Of the 349 participants, 141 (53±15 years old; 21 (15%) men) were cases, 89 (55±16 years old; 11 (12%) men) were in control group 1, 75 (49±15 years old; 25 (33%) men) were in control group 2 and 44 (55±16 years old; 9 (21%) men) were in control group 3.Future plansThe study aims to use a multiorgan score calculated as the cumulative total for each of nine domains (ie, lung, vascular, heart, kidney, brain, autonomic function, muscle strength, exercise capacity and physical performance). The availability of data preceding acute COVID-19 infection in cohorts may help identify the consequences of infection independent of pre-existing subclinical disease and also provide evidence of determinants that influence the development of long covid.

Background : Most biomedical research has focused on sampling COVID-19 patients presenting to hospital with advanced disease, with less focus on the asymptomatic or paucisymptomatic. We established a bioresource with serial sampling of health care workers (HCWs) designed to obtain samples before and during mainly mild disease, with follow-up sampling to evaluate the quality and duration of immune memory. Methods : We conducted a prospective study on HCWs from three hospital sites in London, initially at a single centre (recruited just prior to first peak community transmission in London), but then extended to multiple sites 3 weeks later (recruitment still ongoing, target n=1,000). Asymptomatic participants attending work complete a health questionnaire, and provide a nasal swab (for SARS-CoV-2 RNA by RT-PCR tests) and blood samples (mononuclear cells, serum, plasma, RNA and DNA are biobanked) at 16 weekly study visits, and at 6 and 12 months. Results : Preliminary baseline results for the first 731 HCWs (400 single-centre, 331 multicentre extension) are presented. Mean age was 38±11 years; 67% are female, 31% nurses, 20% doctors, and 19% work in intensive care units. COVID-19-associated risk factors were: 37% black, Asian or minority ethnicities; 18% smokers; 13% obesity; 11% asthma; 7% hypertension and 2% diabetes mellitus. At baseline, 41% reported symptoms in the preceding 2 weeks. Preliminary test results from the initial cohort (n=400) are available: PCR at baseline for SARS-CoV-2 was positive in 28 of 396 (7.1%, 95% CI 4.9-10.0%) and 15 of 385 (3.9%, 2.4-6.3%) had circulating IgG antibodies. Conclusions : This COVID-19 bioresource established just before the peak of infections in the UK will provide longitudinal assessments of incident infection and immune responses in HCWs through the natural time course of disease and convalescence. The samples and data from this bioresource are available to academic collaborators by application  https://covid-consortium.com/application-for-samples/ .

Background: The mechanism for traumatic ruptures of the native anterior cruciate ligament (ACL) is frequently a noncontact injury involving a valgus moment with internal rotation of the tibia. The abnormal rotation and translation of the lateral femoral condyle posteroinferiorly relative to the lateral tibial plateau is thought to be related to the geometry of the tibial plateau. Purpose/Hypothesis: The purpose of the study was to mathematically model the posterior tibial plateau geometry in patients with ACL injuries and compare it with that of matched controls. The hypothesis was that increased convexity and steepness of the posterior aspect of the lateral plateau would subject knees to higher forces, leading to a potentially higher risk of ACL injury. Study Design: Cross-sectional study; Level of evidence, 3. Methods: We mathematically modeled the posterior curvature of the lateral tibial plateau in 64 patients with ACL injuries and 68 matched controls. Using sagittal magnetic resonance imaging scans of the knee, points on the articular cartilage of the posterolateral tibial plateau were selected and curve-fitted to a power function (y = a × xn ). For coefficient a and coefficient n, both variables modulated the shape of the curve, where a larger magnitude represented an increase in slope steepness. Groups were compared using a Mann-Whitney test and α < .05. Results: There was a significant difference in surface geometry between the patients with ACL injuries and matched controls. The equation coefficients were significantly larger in the patients with ACL injuries: coefficient a (ACL injury, 0.9 vs control, 0.68; P < .0001) and coefficient n (ACL injury, 0.34 vs control, 0.30; P = .07). For coefficient a, there was a 78.9% sensitivity, 77.5% specificity, and odds ratio of 12.6 (95% CI, 5.5-29.0) for ACL injury using a cutoff coefficient a = .78. Conclusion: Patients with ACL injuries had a significantly greater posterolateral plateau slope. The steeper drop off may play a role in higher anterior translation forces, coupled with internal rotation torques on the knee in noncontact injury, which could increase ACL strain and predispose to ACL injury.

Individuals with potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not necessarily develop PCR or antibody positivity, suggesting that some individuals may clear subclinical infection before seroconversion. T cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections 1 – 3 . Here we hypothesize that pre-existing memory T cell responses, with cross-protective potential against SARS-CoV-2 (refs. 4 – 11 ), would expand in vivo to support rapid viral control, aborting infection. We measured SARS-CoV-2-reactive T cells, including those against the early transcribed replication–transcription complex (RTC) 12 , 13 , in intensively monitored healthcare workers (HCWs) who tested repeatedly negative according to PCR, antibody binding and neutralization assays (seronegative HCWs (SN-HCWs)). SN-HCWs had stronger, more multispecific memory T cells compared with a cohort of unexposed individuals from before the pandemic (prepandemic cohort), and these cells were more frequently directed against the RTC than the structural-protein-dominated responses observed after detectable infection (matched concurrent cohort). SN-HCWs with the strongest RTC-specific T cells had an increase in IFI27 , a robust early innate signature of SARS-CoV-2 (ref. 14 ), suggesting abortive infection. RNA polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and SARS-CoV-2 clades. RNA polymerase was preferentially targeted (among the regions tested) by T cells from prepandemic cohorts and SN-HCWs. RTC-epitope-specific T cells that cross-recognized HCoV variants were identified in SN-HCWs. Enriched pre-existing RNA-polymerase-specific T cells expanded in vivo to preferentially accumulate in the memory response after putative abortive compared to overt SARS-CoV-2 infection. Our data highlight RTC-specific T cells as targets for vaccines against endemic and emerging Coronaviridae . Seronegative healthcare workers with an innate signature of infection preferentially expand pre-existing T cells targeting the conserved replication transcription complex of SARS-CoV-2 in abortive infection.

BackgroundCurrent electrocardiographic (ECG) devices built into cardiovascular magnetic resonance (CMR) scanners have a narrow bandwidth (0.5–60Hz) and signals suffer from distortion due to magnetic field gradient artefact and magnetohydrodynamic effects, so ECGs are non-diagnostic except for R-peak detection. Despite advanced QRS detection algorithms, incorrect R peak detection hampers image acquisition, especially at higher field strengths, thus prolonging scan time and producing suboptimal images. Previous feasibility studies at 1.5 and 3 Tesla (T) using external ECG devices were small: n=14 and n=4 healthy volunteers respectively. We implemented a novel hardware and software system for integrating an external device into a clinical 3T CMR scanner to derive diagnostic 12-lead ECGs from inside the scanner bore and during stress perfusion acquisition.MethodsStandard 12-lead ECGs were first recorded on participants of the MyoFit46 cardiovascular sub-study of the National Survey of Health and Development outside the CMR environment using conventional electrode placement. CMR was then performed using Siemens Prisma 3T magnet. Three electrodes (each with 3 measurement and 1 reference electrodes, figure 1a) were applied to the chest of participants. Short leads connected each electrode to a sensor for signal amplification and digitalisation (figure 1b). Signals were then transmitted via 10 m-long dual fibre-optic cables running through a penetration hole into the adjacent room to reach an electronics signal module and connected laptop (32 cores, 5.2GHz) equipped with easyG/truzyG/Epsidy software (figure 1c). ECGs were recorded for 30 seconds prior to image acquisition in all participants and repeated during stress perfusion acquisition in one participant as proof-of-principle. Post-processing denoise filtering removed gradient artefact and a subject-specific matrix was applied to reconstruct 12-lead ECGs from the raw signal. The morphology of each beat of the in-bore 12-lead ECG was compared to the reference ECG (outside the scanner) using Pearson’s correlation coefficient on the PQRST waveform.Results20 participants were prospectively recruited (60% male, 76±0 years). In-bore 12-lead ECGs were safe and successfully reconstructed in all cases (3 examples at rest: figures 2A-C). The reconstructed 12-lead ECGs (red lines) correlated closely with the standard ECGs (green lines)- mean correlation coefficient r=0.86 (95% confidence interval 0.82;0.90) when comparing PQRST morphology. The mean difference (MD) in QRS duration between ECGs was 4 ms (limit of agreement [LOA] -17 to 25 ms) and MD in cQT interval 1 ms(LOA -22 to 21 ms).ECG recording during adenosine infusion proved feasible in the exemplar (figure 2D- green line, same participant as figure 2C). Recording at peak stress (after 4 minutes of adenosine) showed evolving ST elevation in leads II, III, aVf, V1 and V2 and ST depression in I and aVl.ConclusionHigh-quality diagnostic 12-lead ECGs can be collected in real-time during a 3T CMR scan with potential to improve triggering and image acquisition. Our ability to detect transient ischaemic changes during stress perfusion may enhance the interpretation of quantitative perfusion maps and the technology may have several neurocardiology applications.Abstract BS19 Figure 1A) Example electrode patch with 3 separate measurement electrodes and 1 reference (black) electrode. B) Electrode configuration on a participant’s chest (if female, lateral electrode is positioned under the breast). Each electrode connects to a sensor (grey box) via a short lead (black line) for signal amplification and digitalization. Short leads prevent overheating from the radiofrequency gradient minimizing the risk of burns. C) Hardware set-up inside and out of the CMR environment. Cables are bound together and passed through a penetration hole to reach the adjacent control roomAbstract BS19 Figure 2A, B and C) Examples from 3 participants each showing reference 12-lead ECG from outside the CMR environment (green line) and superimposed reconstructed 12-lead ECG from inside the CMR bore (red line). A: mean correlation 89.7%; B mean correlation 90.1%; C: mean correlation 76.7%. D) Feasibility of 12-lead ECG recording during adenosine stress perfusion for same participant as figure 2D showing ST elevation in leads II, III , aVf, V1 and V2 and ST depression in I and aVl when compared to the resting in-bore ECGConflict of InterestNo

Background The life course accumulation of overt and subclinical myocardial dysfunction contributes to older age mortality, frailty, disability and loss of independence. The Medical Research Council National Survey of Health and Development (NSHD) is the world’s longest running continued surveillance birth cohort providing a unique opportunity to understand life course determinants of myocardial dysfunction as part of MyoFit46–the cardiac sub-study of the NSHD. Methods We aim to recruit 550 NSHD participants of approximately 75 years+ to undertake high-density surface electrocardiographic imaging (ECGI) and stress perfusion cardiovascular magnetic resonance (CMR). Through comprehensive myocardial tissue characterization and 4-dimensional flow we hope to better understand the burden of clinical and subclinical cardiovascular disease. Supercomputers will be used to combine the multi-scale ECGI and CMR datasets per participant. Rarely available, prospectively collected whole-of-life data on exposures, traditional risk factors and multimorbidity will be studied to identify risk trajectories, critical change periods, mediators and cumulative impacts on the myocardium. Discussion By combining well curated, prospectively acquired longitudinal data of the NSHD with novel CMR–ECGI data and sharing these results and associated pipelines with the CMR community, MyoFit46 seeks to transform our understanding of how early, mid and later-life risk factor trajectories interact to determine the state of cardiovascular health in older age. Trial registration : Prospectively registered on ClinicalTrials.gov with trial ID: 19/LO/1774 Multimorbidity Life-Course Approach to Myocardial Health- A Cardiac Sub-Study of the MCRC National Survey of Health and Development (NSHD).

Background : Most biomedical research has focused on sampling COVID-19 patients presenting to hospital with advanced disease, with less focus on the asymptomatic or paucisymptomatic. We established a bioresource with serial sampling of health care workers (HCWs) designed to obtain samples before and during mainly mild disease, with follow-up sampling to evaluate the quality and duration of immune memory. Methods : We conducted a prospective observational study on HCWs from three hospital sites in London, initially at a single centre (recruited just prior to first peak community transmission in London), but then extended to multiple sites 3 weeks later (recruitment still ongoing, target n=1,000). Asymptomatic participants attending work complete a health questionnaire, and provide a nasal swab (for SARS-CoV-2 RNA by RT-PCR tests) and blood samples (mononuclear cells, serum, plasma, RNA and DNA are biobanked) at 16 weekly study visits, and at 6 and 12 months. Results : Preliminary baseline results for the first 731 HCWs (400 single-centre, 331 multicentre extension) are presented. Mean age was 38±11 years; 67% are female, 31% nurses, 20% doctors, and 19% work in intensive care units. COVID-19-associated risk factors were: 37% black, Asian or minority ethnicities; 18% smokers; 13% obesity; 11% asthma; 7% hypertension and 2% diabetes mellitus. At baseline, 41% reported symptoms in the preceding 2 weeks. Preliminary test results from the initial cohort (n=400) are available: PCR at baseline for SARS-CoV-2 was positive in 28 of 396 (7.1%, 95% CI 4.9-10.0%) and 15 of 385 (3.9%, 2.4-6.3%) had circulating IgG antibodies. Conclusions : This COVID-19 bioresource established just before the peak of infections in the UK will provide longitudinal assessments of incident infection and immune responses in HCWs through the natural time course of disease and convalescence. The samples and data from this bioresource are available to academic collaborators by application  https://covid-consortium.com/application-for-samples/ .

Heterogeneous Computing with OpenCL, Second Edition teaches OpenCL and parallel programming for complex systems that may include a variety of device architectures: multi-core CPUs, GPUs, and fully-integrated Accelerated Processing Units (APUs) such as AMD Fusion technology. It is the first textbook that presents OpenCL programming appropriate for the classroom and is intended to support a parallel programming course. Students will come away from this text with hands-on experience and significant knowledge of the syntax and use of OpenCL to address a range of fundamental parallel algorithms.Designed to work on multiple platforms and with wide industry support, OpenCL will help you more effectively program for a heterogeneous future. Written by leaders in the parallel computing and OpenCL communities, Heterogeneous Computing with OpenCL explores memory spaces, optimization techniques, graphics interoperability, extensions, and debugging and profiling. It includes detailed examples throughout, plus additional online exercises and other supporting materials that can be downloaded at http://www.heterogeneouscompute.org/?page_id=7This book will appeal to software engineers, programmers, hardware engineers, and students/advanced students.Explains principles and strategies to learn parallel programming with OpenCL, from understanding the four abstraction models to thoroughly testing and debugging complete applications.Covers image processing, web plugins, particle simulations, video editing, performance optimization, and more.Shows how OpenCL maps to an example target architecture and explains some of the tradeoffs associated with mapping to various architecturesAddresses a range of fundamental programming techniques, with multiple examples and case studies that demonstrate OpenCL extensions for a variety of hardware platforms