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1. The association between time of in hospital cardiac arrest and mortality; a retrospective analysis of two UK databases

Author: McGuigan, Peter J, Edwards, Julia, Blackwood, Bronagh, Dark, Paul, Doidge, James C, Harrison, David A, Kitchen, Gareth, Lawson, Izabella, Nichol, Alistair D, Rowan, Kathryn M, Shankar-Hari, Manu, and McAuley, Danny F
Subjects: Critical care, Circadian rhythm, Emergency Medicine, Emergency Nursing, Mortality, Cardiology and Cardiovascular Medicine, Cardiac arrest
Abstract: Aims: The incidence of in hospital cardiac arrest (IHCA) varies throughout the day. This study aimed to report the variation in incidence of IHCA, presenting rhythm and outcome based on the hour in which IHCA occurred. Methods: We conducted a retrospective analysis of the National Cardiac Arrest Audit (NCAA) including patients who suffered an IHCA from 1st April 2011 to 31st December 2019. We then linked the NCAA and intensive care Case Mix Programme databases to explore the effect of time of IHCA on hospital survival in the subgroup of patients admitted to intensive care following IHCA. Results: We identified 115,690 eligible patients in the NCAA database. Pulseless electrical activity was the commonest presenting rhythm (54.8%). 66,885 patients died in the immediate post resuscitation period. Overall, hospital survival in the NCAA cohort was 21.3%. We identified 13,858 patients with linked ICU admissions in the Case Mix Programme database; 37.0% survived to hospital discharge. The incidence of IHCA peaked at 06.00. Rates of return of spontaneous circulation, survival to hospital discharge and good neurological outcome were lowest between 05.00 and 07.00. Among those admitted to ICU, no clear diurnal variation in hospital survival was seen in the unadjusted or adjusted analysis. This pattern was consistent across all presenting rhythms. Conclusions: We observed higher rates of IHCA, and poorer outcomes at night. However, in those admitted to ICU, this variation was absent. This suggests patient factors and processes of care issues contribute to the variation in IHCA seen throughout the day.
Published: 2023
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2. A Machine Learning Tutorial for Operational Meteorology, Part II: Neural Networks and Deep Learning

Author: Chase, Randy J., Harrison, David R., Lackmann, Gary, and McGovern, Amy
Subjects: FOS: Computer and information sciences, Computer Science - Machine Learning, Physics - Atmospheric and Oceanic Physics, Atmospheric Science, Computer Vision and Pattern Recognition (cs.CV), Atmospheric and Oceanic Physics (physics.ao-ph), Computer Science - Computer Vision and Pattern Recognition, FOS: Physical sciences, Machine Learning (cs.LG)
Abstract: Over the past decade the use of machine learning in meteorology has grown rapidly. Specifically neural networks and deep learning have been used at an unprecedented rate. In order to fill the dearth of resources covering neural networks with a meteorological lens, this paper discusses machine learning methods in a plain language format that is targeted for the operational meteorological community. This is the second paper in a pair that aim to serve as a machine learning resource for meteorologists. While the first paper focused on traditional machine learning methods (e.g., random forest), here a broad spectrum of neural networks and deep learning methods are discussed. Specifically this paper covers perceptrons, artificial neural networks, convolutional neural networks and U-networks. Like the part 1 paper, this manuscript discusses the terms associated with neural networks and their training. Then the manuscript provides some intuition behind every method and concludes by showing each method used in a meteorological example of diagnosing thunderstorms from satellite images (e.g., lightning flashes). This paper is accompanied with an open-source code repository to allow readers to explore neural networks using either the dataset provided (which is used in the paper) or as a template for alternate datasets.
Published: 2023
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3. Deep Multiple Instance Learning with Distance-Aware Self-Attention

Author: Wölflein, Georg, Magister, Lucie Charlotte, Liò, Pietro, Harrison, David J., and Arandjelović, Ognjen
Subjects: FOS: Computer and information sciences, Computer Science - Machine Learning, Computer Vision and Pattern Recognition (cs.CV), Computer Science - Computer Vision and Pattern Recognition, Machine Learning (cs.LG)
Abstract: Traditional supervised learning tasks require a label for every instance in the training set, but in many real-world applications, labels are only available for collections (bags) of instances. This problem setting, known as multiple instance learning (MIL), is particularly relevant in the medical domain, where high-resolution images are split into smaller patches, but labels apply to the image as a whole. Recent MIL models are able to capture correspondences between patches by employing self-attention, allowing them to weigh each patch differently based on all other patches in the bag. However, these approaches still do not consider the relative spatial relationships between patches within the larger image, which is especially important in computational pathology. To this end, we introduce a novel MIL model with distance-aware self-attention (DAS-MIL), which explicitly takes into account relative spatial information when modelling the interactions between patches. Unlike existing relative position representations for self-attention which are discrete, our approach introduces continuous distance-dependent terms into the computation of the attention weights, and is the first to apply relative position representations in the context of MIL. We evaluate our model on a custom MNIST-based MIL dataset that requires the consideration of relative spatial information, as well as on CAMELYON16, a publicly available cancer metastasis detection dataset, where we achieve a test AUROC score of 0.91. On both datasets, our model outperforms existing MIL approaches that employ absolute positional encodings, as well as existing relative position representation schemes applied to MIL. Our code is available at https://anonymous.4open.science/r/das-mil.
Published: 2023

4. Impact of different mammography systems on artificial intelligence performance in breast cancer screening

Author: de Vries, Clarisse F., Colosimo, Samantha J., Staff, Roger T., Dymiter, Jaroslaw A., Yearsley, Joseph, Dinneen, Deirdre, Boyle, Moragh, Harrison, David J., Anderson, Lesley A., Lip, Gerald, Black, Corri, Murray, Alison D., Wilde, Katie, Blackwood, James D., Butterly, Claire, Zurowski, John, Eilbeck, Jon, McSkimming, Colin, Innovate UK, University of St Andrews. School of Medicine, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, and University of St Andrews. Cellular Medicine Division
Subjects: MCC, RC0254, SDG 3 - Good Health and Well-being, RC0254 Neoplasms. Tumors. Oncology (including Cancer), primary [Neoplasms], Screening, Breast, Technology assessment, 3rd-DAS, detection/diagnosis [Computer applications], Mammography
Abstract: Funding: Supported by the Industrical Centre of Artificial Intelligence Research in Digital Diagnosis (iCAIRD), which is funded by Innovate UK on behalf of UK Research and Innovation (UKRI) (project no. 104690). Artificial intelligence (AI) tools may assist breast screening mammography programs, but limited evidence supports their generalizability to new settings. This retrospective study used a 3-year dataset (April 1, 2016-March 31, 2019) from a U.K. regional screening program. The performance of a commercially available breast screening AI algorithm was assessed with a prespecified and site-specific decision threshold to evaluate whether its performance was transferable to a new clinical site. The dataset consisted of women (aged approximately 50-70 years) who attended routine screening, excluding self-referrals, those with complex physical requirements, those who had undergone a previous mastectomy, and those who underwent screening that had technical recalls or did not have the four standard image views. In total, 55916 screening attendees (mean age, 60 years ± 6 [SD]) met the inclusion criteria. The prespecified threshold resulted in high recall rates (48.3%, 21929 of 45444), which reduced to 13.0% (5896 of 45444) following threshold calibration, closer to the observed service level (5.0%, 2774 of 55916). Recall rates also increased approximately threefold following a software upgrade on the mammography equipment, requiring per-software version thresholds. Using software-specific thresholds, the AI algorithm would have recalled 277 of 303 (91.4%) screen-detected cancers and 47 of 138 (34.1%) interval cancers. AI performance and thresholds should be validated for new clinical settings before deployment, while quality assurance systems should monitor AI performance for consistency. Postprint
Published: 2023

5. Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial

Author: Writing Committee for the REMAP-CAP Investigators, Lawler, Patrick R, Derde, Lennie PG, van de Veerdonk, Frank L, McVerry, Bryan J, Huang, David T, Berry, Lindsay R, Lorenzi, Elizabeth, van Kimmenade, Roland, Gommans, Frank, Vaduganathan, Muthiah, Leaf, David E, Baron, Rebecca M, Kim, Edy Y, Frankfurter, Claudia, Epelman, Slava, Kwan, Yvonne, Grieve, Richard, O'Neill, Stephen, Sadique, Zia, Puskarich, Michael, Marshall, John C, Higgins, Alisa M, Mouncey, Paul R, Rowan, Kathryn M, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Au, Carly, Beane, Abi, van Bentum-Puijk, Wilma, Bonten, Marc JM, Bradbury, Charlotte A, Brunkhorst, Frank M, Burrell, Aidan, Buzgau, Adrian, Buxton, Meredith, Cecconi, Maurizio, Cheng, Allen C, Cove, Matthew, Detry, Michelle A, Estcourt, Lise J, Ezekowitz, Justin, Fitzgerald, Mark, Gattas, David, Godoy, Lucas C, Goossens, Herman, Haniffa, Rashan, Harrison, David A, Hills, Thomas, Horvat, Christopher M, Ichihara, Nao, Lamontagne, Francois, Linstrum, Kelsey M, McAuley, Daniel F, McGlothlin, Anna, McGuinness, Shay P, McQuilten, Zoe, Murthy, Srinivas, Nichol, Alistair D, Owen, David RJ, Parke, Rachael L, Parker, Jane C, Pollock, Katrina M, Reyes, Luis Felipe, Saito, Hiroki, Santos, Marlene S, Saunders, Christina T, Seymour, Christopher W, Shankar-Hari, Manu, Singh, Vanessa, Turgeon, Alexis F, Turner, Anne M, Zarychanski, Ryan, Green, Cameron, Lewis, Roger J, Angus, Derek C, Berry, Scott, Gordon, Anthony C, McArthur, Colin J, Webb, Steve A, and Apollo - University of Cambridge Repository
Subjects: Male, Renin-Angiotensin System, Hospitalization, Angiotensin Receptor Antagonists, Critical Illness, Humans, COVID-19, Female, Angiotensin-Converting Enzyme Inhibitors, Bayes Theorem, Receptors, Chemokine, Middle Aged, COVID-19 Drug Treatment
Abstract: IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES: The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS: On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE: In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.
Published: 2023

6. Impact of Different Mammography Systems on Artificial Intelligence Performance in Breast Cancer Screening

Author: de Vries, Clarisse F., Colosimo, Samantha J., Staff, Roger T., Dymiter, Jaroslaw A., Yearsley, Joseph, Dinneen, Deirdre, Boyle, Moragh, Harrison, David J., Anderson, Lesley A., and Lip, Gerald
Subjects: AI in Brief
Abstract: Artificial intelligence (AI) tools may assist breast screening mammography programs, but limited evidence supports their generalizability to new settings. This retrospective study used a 3-year dataset (April 1, 2016–March 31, 2019) from a U.K. regional screening program. The performance of a commercially available breast screening AI algorithm was assessed with a prespecified and site-specific decision threshold to evaluate whether its performance was transferable to a new clinical site. The dataset consisted of women (aged approximately 50–70 years) who attended routine screening, excluding self-referrals, those with complex physical requirements, those who had undergone a previous mastectomy, and those who underwent screening that had technical recalls or did not have the four standard image views. In total, 55 916 screening attendees (mean age, 60 years ± 6 [SD]) met the inclusion criteria. The prespecified threshold resulted in high recall rates (48.3%, 21 929 of 45 444), which reduced to 13.0% (5896 of 45 444) following threshold calibration, closer to the observed service level (5.0%, 2774 of 55 916). Recall rates also increased approximately threefold following a software upgrade on the mammography equipment, requiring per–software version thresholds. Using software-specific thresholds, the AI algorithm would have recalled 277 of 303 (91.4%) screen-detected cancers and 47 of 138 (34.1%) interval cancers. AI performance and thresholds should be validated for new clinical settings before deployment, while quality assurance systems should monitor AI performance for consistency. Keywords: Breast, Screening, Mammography, Computer Applications–Detection/Diagnosis, Neoplasms-Primary, Technology Assessment Supplemental material is available for this article. © RSNA, 2023
Published: 2023

7. Balancing renewable energy and river resources by moving from individual assessments of hydropower projects to energy system planning

Author: Opperman, Jeffrey J., Carvallo, Juan Pablo, Kelman, Rafael, Schmitt, Rafael J. P., Almeida, Rafael, Chapin, Emily, Flecker, Alexander, Goichot, Marc, Grill, Guenther, Harou, Julien J., Hartmann, Joerg, Higgins, Jonathan, Kammen, Daniel, Martin, Erik, Martins, Taina, Newsock, Amy, Rogéliz, Carlos, Raepple, Justus, Sada, Rajesh, Thieme, Michele L., and Harrison, David
Subjects: General Environmental Science
Abstract: As governments and non-state actors strive to minimize global warming, a primary strategy is the decarbonization of power systems which will require a massive increase in renewable electricity generation. Leading energy agencies forecast a doubling of global hydropower capacity as part of that necessary expansion of renewables. While hydropower provides generally low-carbon generation and can integrate variable renewables, such as wind and solar, into electrical grids, hydropower dams are one of the primary reasons that only one-third of the world’s major rivers remain free-flowing. This loss of free-flowing rivers has contributed to dramatic declines of migratory fish and sediment delivery to agriculturally productive deltas. Further, the reservoirs behind dams have displaced tens of millions of people. Thus, hydropower challenges the world’s efforts to meet climate targets while simultaneously achieving other Sustainable Development Goals. In this paper, we explore strategies to achieve the needed renewable energy expansion while sustaining the diverse social and environmental benefits of rivers. These strategies can be implemented at scales ranging from the individual project (environmental flows, fish passage and other site-level mitigation) to hydropower cascades to river basins and regional electrical power systems. While we review evidence that project-level management and mitigation can reduce environmental and social costs, we posit that the most effective scale for finding balanced solutions occurs at the scale of power systems. We further hypothesize that the pursuit of solutions at the system scale can also provide benefits for investors, developers and governments; evidence of benefits to these actors will be necessary for achieving broad uptake of the approaches described in this paper. We test this hypothesis through cases from Chile and Uganda that demonstrate the potential for system-scale power planning to allow countries to meet low-carbon energy targets with power systems that avoid damming high priority rivers (e.g., those that would cause conflicts with other social and environmental benefits) for a similar system cost as status quo approaches. We also show that, through reduction of risk and potential conflict, strategic planning of hydropower site selection can improve financial performance for investors and developers, with a case study from Colombia.
Published: 2023
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8. Werede A. AIDS conference_2022_CW.pdf

Author: Werede, Ayoda, Terry, James G., Nair, Sangeeta, Temu, Tecla M., E Shepherd, Bryan, Bailin, Samuel, Mashayekhi, Mona, Gabriel, Curtis L., Lima, Morgan, Woodward, Beverly O., Hannah, LaToya, Mallal, Simon A., Beckman, Joshua A, Z. Li, Jonathan, Fajnzylber, Jesse, G. Harrison, David, Carr, John Jeffrey, Koethe, John R., and Wanjalla, Celestine N.
Subjects: Virology, Infectious agents
Abstract: IAS Poster Presentation
Published: 2023
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9. The renal lineage factor PAX8 controls oncogenic signalling in kidney cancer

Author: Patel, Saroor A, Hirosue, Shoko, Rodrigues, Paulo, Vojtasova, Erika, Richardson, Emma K, Ge, Jianfeng, Syafruddin, Saiful E, Speed, Alyson, Papachristou, Eva, Baker, David, Clarke, David, Purvis, Stephenie, Wesolowski, Ludovic, Dyas, Anna, Castillon, Leticia, Caraffini, Veronica, Bihary, Dóra, Yong, Cissy, Harrison, David J, Stewart, Grant, Machiela, Mitchell J, Purdue, Mark P, Chanock, Stephen J, Warren, Anne, Samarajiwa, Shamith A, Carroll, Jason, Vanharanta, Sakari, Hirosue, Shoko [0000-0003-1287-471X], Vojtasova, Erika [0000-0001-9255-8551], Papachristou, Eva [0000-0002-5835-2055], Harrison, David J [0000-0001-9041-9988], Stewart, Grant [0000-0003-3188-9140], Machiela, Mitchell J [0000-0001-6538-9705], Chanock, Stephen J [0000-0002-2324-3393], Warren, Anne [0000-0002-1170-7867], Samarajiwa, Shamith A [0000-0003-1046-0601], Carroll, Jason [0000-0003-3643-0080], Vanharanta, Sakari [0000-0001-5619-7963], Apollo - University of Cambridge Repository, University of St Andrews. School of Medicine, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, CAN-PRO - Translational Cancer Medicine Program, Department of Physiology, Faculty of Medicine, University of Helsinki, Papachristou, Evangelia K [0000-0002-5835-2055], Stewart, Grant D [0000-0003-3188-9140], Warren, Anne Y [0000-0002-1170-7867], and Carroll, Jason S [0000-0003-3643-0080]
Subjects: 82/29, PROMOTES, Carcinogenesis, 45/41, 692/699/67/589/1588/1351, 45/43, SUSCEPTIBILITY, Kidney, 13, 59/5, 59, BINDING, Basic Helix-Loop-Helix Transcription Factors, Cyclin D1, SPECIFICITY, CYCLIN D1, 64, Multidisciplinary, Kidney Neoplasms, Multidisciplinary Sciences, Gene Expression Regulation, Neoplastic, 38/32, 13/31, TARGET, Von Hippel-Lindau Tumor Suppressor Protein, 38/35, Science & Technology - Other Topics, 38/39, 64/60, 631/67/70, Signal Transduction, 3122 Cancers, 13/106, QH426 Genetics, 631/67/69, Article, 38/91, RC0254, ENHANCER, Proto-Oncogene Proteins c-myc, 82/80, PAX8 Transcription Factor, SDG 3 - Good Health and Well-being, 38/89, 631/208/200, HIF, Humans, QH426, Carcinoma, Renal Cell, Alleles, 38/109, 42, Science & Technology, 45, RC0254 Neoplasms. Tumors. Oncology (including Cancer), 82/58, DAS, 45/15, GENE, Mutation, 631/208/191
Abstract: Large-scale human genetic data1-3 have shown that cancer mutations display strong tissue-selectivity, but how this selectivity arises remains unclear. Here, using experimental models, functional genomics and analyses of patient samples, we demonstrate that the lineage transcription factor paired box 8 (PAX8) is required for oncogenic signalling by two common genetic alterations that cause clear cell renal cell carcinoma (ccRCC) in humans: the germline variant rs7948643 at 11q13.3 and somatic inactivation of the von Hippel-Lindau tumour suppressor (VHL)4-6. VHL loss, which is observed in about 90% of ccRCCs, can lead to hypoxia-inducible factor 2α (HIF2A) stabilization6,7. We show that HIF2A is preferentially recruited to PAX8-bound transcriptional enhancers, including a pro-tumorigenic cyclin D1 (CCND1) enhancer that is controlled by PAX8 and HIF2A. The ccRCC-protective allele C at rs7948643 inhibits PAX8 binding at this enhancer and downstream activation of CCND1 expression. Co-option of a PAX8-dependent physiological programme that supports the proliferation of normal renal epithelial cells is also required for MYC expression from the ccRCC metastasis-associated amplicons at 8q21.3-q24.3 (ref. 8). These results demonstrate that transcriptional lineage factors are essential for oncogenic signalling and that they mediate tissue-specific cancer risk associated with somatic and inherited genetic variants., Medical Research Council (MC_UU_12022/7 and MC_UU_12022/10) and Kidney Research UK (RP_033_20170303).
Published: 2022
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10. Interpreting lymphocyte classification from Hoechst stained slides with deep learning

Author: Cooper, Jessica, Um, In Hwa, Arandelovic, Oggie, Harrison, David James, Innovate UK, University of St Andrews. School of Computer Science, University of St Andrews. School of Medicine, University of St Andrews. Cellular Medicine Division, and University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis
Subjects: QA75, Image classification, RC0254 Neoplasms. Tumors. Oncology (including Cancer), QA75 Electronic computers. Computer science, QH301 Biology, Lymphocyte subsets, Deep learning, DAS, Imaging, RC0254, QH301, SDG 3 - Good Health and Well-being, MCP, Computer vision
Abstract: Funding: This work is supported by the Industrial Centre for AI Research in Digital Diagnostics (iCAIRD) which is funded by Innovate UK on behalf of UK Research and Innovation (UKRI) [project number: 104690]. Multiplex immunofluorescence and immunohistochemistry benefit patients by allowing cancer pathologists to identify proteins expressed on the surface of cells. This enables cell classification, better understanding of the tumour microenvironment, and more accurate diagnoses, prognoses, and tailored immunotherapy based on the immune status of individual patients. However, these techniques are expensive. They are time consuming processes which require complex staining and imaging techniques by expert technicians. Hoechst staining is far cheaper and easier to perform, but is not typically used as it binds to DNA rather than to the proteins targeted by immunofluorescence techniques. In this work we show that through the use of deep learning it is possible to identify an immune cell subtype without immunofluorescence. We train a deep convolutional neural network to identify cells expressing the T lymphocyte marker CD3 from Hoechst 33342 stained tissue only. CD3 expressing cells are often used in key prognostic metrics such as assessment of immune cell infiltration, and by identifying them without the need for costly immunofluorescence, we present a promising new approach to cheaper prediction and improvement of patient outcomes. We also show that by using deep learning interpretability techniques, we can gain insight into the previously unknown morphological features which make this possible. Publisher PDF
Published: 2022

11. Moral Foundation Violations and Responses to Anti-Racist Workplace Policies

Author: Harrison, David, Hall, Alison, Bell, Myrtle, Samuel, Naomi, and Garcia, Larissa
Subjects: Moral Foundations, Diversity, Workplace policies, Anti-racism, Social and Behavioral Sciences, Anti-racist policies
Abstract: Experiment jointly examining the impact of the strength of anti-racist policies (ARPs) with the priming of moral foundation violations (MFVs) regarding workplace policies for performance management.
Published: 2022
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12. Can Triggering Moral Foundations Overcome Resistance To Anti-Racist Policies at Work?

Author: Harrison, David, Hall, Alison, Bell, Myrtle, Samuel, Naomi, and Garcia, Larissa
Subjects: anti-racism, moral foundations, Business, Social and Behavioral Sciences, racism, discrimination
Abstract: Our goal for applied psychological science is to identify a theory-driven, pragmatic way to reduce opposition to workplace practices that vigorously confront systemic racism. We blend both organizational systems and psychology, coupling conceptual clarity about what constitutes anti-racist policies with ideas about how moral framing can influence employees’ attitudinal and behavioral responses to them. We will test hypotheses about the main effects of those constructs in three ongoing, methodologically interlocking and triangulating investigations.
Published: 2022
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13. Breast cancer chemotherapy induces vascular dysfunction and hypertension through NOX4 dependent mechanism

Author: Szczepaniak, Piotr, Siedlinski, Mateusz, Hodorowicz-Zaniewska, Diana, Nosalski, Ryszard, Mikolajczyk, Tomasz P., Dobosz, Aneta M., Dikalova, Anna, Dikalov, Sergey, Streb, Joanna, Gara, Katarzyna, Basta, Pawel, Krolczyk, Jaroslaw, Sulicka-Grodzicka, Joanna, Jozefczuk, Ewelina, Dziewulska, Anna, Saju, Blessy, Laksa, Iwona, Chen, Wei, Dormer, John, Tomaszewski, Maciej, Maffia, Pasquale, Czesnikiewicz-Guzik, Marta, Crea, Filippo, Dobrzyn, Agnieszka, Moslehi, Javid, Grodzicki, Tomasz, Harrison, David G., and Guzik, Tomasz J.
Abstract: Cardiovascular disease is the major cause of morbidity and mortality in breast cancer survivors. Chemotherapy contributes to this risk. We aimed to define the mechanisms of long-term vascular dysfunction caused by neoadjuvant chemotherapy (NACT) and identify novel therapeutic targets.\ud \ud We studied arteries from postmenopausal women who had undergone breast cancer treatment using docetaxel, doxorubicin and cyclophosphamide (NACT), and women with no history of such treatment matched for key clinical parameters. Mechanisms were explored in wild-type and Nox4-/- mice and human microvascular endothelial cells.\ud \ud Endothelium-dependent vasodilatation is severely impaired in patients after NACT, while endothelium-independent responses remain normal. This was mimicked by 24-hour exposure of arteries to NACT agents ex-vivo. When applied individually, only docetaxel impaired endothelial function in human vessels. Mechanistic studies showed that NACT increased inhibitory eNOS phosphorylation of threonine 495 in a ROCK-dependent manner and augmented vascular superoxide and hydrogen peroxide production and NADPH oxidase activity. Docetaxel increased expression of NADPH oxidase NOX4 in endothelial and smooth muscle cells and NOX2 in the endothelium. NOX4 increase in human arteries may be mediated epigenetically by diminished DNA methylation of the NOX4 promoter. Docetaxel induced endothelial dysfunction and hypertension in mice. These were prevented in Nox4-/- and by pharmacological inhibition of Nox4 or Rock.\ud \ud Commonly used chemotherapeutic agents, and in particular, docetaxel, alter vascular function by promoting inhibitory phosphorylation of eNOS and enhancing ROS production by NADPH oxidases.
Published: 2022

14. Incidence and factors related to SARS-CoV-2 infection in a cohort of patients with rheumatoid arthritis from a health service provider in Colombia during the COVID-19 pandemic

Author: Luis Fernando Valladales-Restrepo, Manuel Enrique Machado-Duque, Andrés Gaviria-Mendoza, Harrison David Ospina-Arzuaga, Maritza Ruiz-Zapata, and Jorge Enrique Machado-Alba
Subjects: Infectious Diseases, Pharmacology (medical)
Abstract: Background: Patients with rheumatoid arthritis (RA) have an increased risk of SARS-CoV-2 infection due to intrinsic characteristics of the pathology and the medications used to treat it. The aim was to evaluate the incidence of and factors related to SARS-CoV-2 infection in patients with RA in Colombia. Methods: This was an observational study of patients diagnosed with RA who were treated at a health care institution in Colombia. The study evaluated whether the patients presented SARS-CoV-2 infection and other clinical variables. Variables associated with the risk of SARS-CoV-2 infection were identified. Results: A total of 2566 patients with RA were identified. They had a median age of 61.9 years, and 81.1% were women. They were mainly treated with synthetic disease-modifying antirheumatic drugs (DMARDs) (85.3%), glucocorticoids (52.2%), and biological DMARDs (26.8%). The incidence of SARS-CoV-2 infection was 5.1%, and the factors that increased the risk included treatment with synthetic DMARDs with or without biological DMARDs but with concomitant systemic glucocorticoids [odds ratio (OR): 2.18, 95% confidence interval (CI): 1.21–3.93 and OR: 1.69, 95% CI: 1.05–2.74, respectively] and receiving antidiabetic drugs (OR: 2.24, 95% CI: 1.27–3.94). A total of 20.8% of patients with COVID-19 required hospitalization and 3.8% died. Conclusion: The incidence of COVID-19 is higher among patients with RA who receive DMARDs and glucocorticoids simultaneously or who have diabetes mellitus than among patients with RA not receiving these drug combinations, which should guide treatment strategies.
Published: 2022

15. COVID-19 in critical care: epidemiology of the first epidemic wave across England, Wales and Northern Ireland

Author: Richards-Belle, Alvin, Orzechowska, Izabella, Gould, Doug W., Thomas, Karen, Doidge, James C., Mouncey, Paul R., Christian, Michael D., Shankar-Hari, Manu, Harrison, David A., Rowan, Kathryn M., Banjo, Yemi, Borowczak, Kasia, Cousins, Tom, Cummins, Peter, Dalemo, Keji, Darnell, Robert, Demissie, Hanna, Drikite, Laura, Fleming, Andrew, Frederiksen, Ditte, Furnell, Sarah, Hussein, Abdo, Koelewyn, Abby, Matthews, Tim, Peters, Sam, Samuels, Tyrone, and Saull, Michelle
Subjects: Clinical audit, medicine.medical_specialty, Pandemic, business.industry, Original, COVID-19, 030208 emergency & critical care medicine, Retrospective cohort study, Outcomes, Critical Care and Intensive Care Medicine, medicine.disease, Comorbidity, Coronavirus, 03 medical and health sciences, Critical care, 0302 clinical medicine, Case mix index, 030228 respiratory system, Emergency medicine, Cohort, Epidemiology, medicine, business, Prospective cohort study, Cohort study
Abstract: Purpose To describe critical care patients with COVID-19 across England, Wales and Northern Ireland and compare them with a historic cohort of patients with other viral pneumonias (non-COVID-19) and with international cohorts of COVID-19. Methods Extracted data on patient characteristics, acute illness severity, organ support and outcomes from the Case Mix Programme, the national clinical audit for adult critical care, for a prospective cohort of patients with COVID-19 (February to August 2020) are compared with a recent retrospective cohort of patients with other viral pneumonias (non-COVID-19) (2017–2019) and with other international cohorts of critical care patients with COVID-19, the latter identified from published reports. Results 10,834 patients with COVID-19 (70.1% male, median age 60 years, 32.6% non-white ethnicity, 39.4% obese, 8.2% at least one serious comorbidity) were admitted across 289 critical care units. Of these, 36.9% had a PaO2/FiO2 ratio of ≤ 13.3 kPa (≤ 100 mmHg) consistent with severe ARDS and 72% received invasive ventilation. Acute hospital mortality was 42%, higher than for 5782 critical care patients with other viral pneumonias (non-COVID-19) (24.7%), and most COVID-19 deaths (88.7%) occurred before 30 days. Meaningful international comparisons were limited due to lack of standardised reporting. Conclusion Critical care patients with COVID-19 were disproportionately non-white, from more deprived areas and more likely to be male and obese. Conventional severity scoring appeared not to adequately reflect their acute severity, with the distribution across PaO2/FiO2 ratio categories indicating acutely severe respiratory disease. Critical care patients with COVID-19 experience high mortality and place a great burden on critical care services. Electronic supplementary material The online version of this article (10.1007/s00134-020-06267-0) contains supplementary material, which is available to authorized users.
Published: 2020

16. OpenSAFELY: factors associated with COVID-19 death in 17 million patients

Author: Williamson, Elizabeth J, Walker, Alex J, Bhaskaran, Krishnan, Bacon, Seb, Bates, Chris, Morton, Caroline E, Curtis, Helen J, Mehrkar, Amir, Evans, David, Inglesby, Peter, Cockburn, Jonathan, McDonald, Helen I, MacKenna, Brian, Tomlinson, Laurie, Douglas, Ian J, Rentsch, Christopher T, Mathur, Rohini, Wong, Angel YS, Grieve, Richard, Harrison, David, Forbes, Harriet, Schultze, Anna, Croker, Richard, Parry, John, Hester, Frank, Harper, Sam, Perera, Rafael, Evans, Stephen JW, Smeeth, Liam, and Goldacre, Ben
Subjects: SARS-CoV-2, Pneumonia, Viral, COVID-19, Article, Asthma, deprivation, Betacoronavirus, death, risk factors, ethnicity, informatics, Humans, Coronavirus Infections, Pandemics
Abstract: Summary COVID-19 has rapidly impacted on mortality worldwide.1 There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets. Working on behalf of NHS England we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor. Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19 related deaths. COVID-19 related death was associated with: being male (hazard ratio 1.59, 95%CI 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared to people with white ethnicity, black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.29-1.69 and 1.45, 1.32-1.58 respectively). We have quantified a range of clinical risk factors for COVID-19 related death in the largest cohort study conducted by any country to date. OpenSAFELY is rapidly adding further patients’ records; we will update and extend results regularly.
Published: 2020

17. Quasiparticle Poisoning of Superconducting Qubits from Resonant Absorption of Pair-breaking Photons

Author: Liu, Chuan-Hong, Harrison, David C., Patel, Shravan, Wilen, Christopher D., Rafferty, Owen, Shearrow, Abigail, Ballard, Andrew, Iaia, Vito, Ku, Jaseung, Plourde, Britton L. T., and McDermott, Robert
Subjects: Quantum Physics, Computer Science::Emerging Technologies, Condensed Matter::Superconductivity, FOS: Physical sciences, Quantum Physics (quant-ph)
Abstract: The ideal superconductor provides a pristine environment for the delicate states of a quantum computer: because there is an energy gap to excitations, there are no spurious modes with which the qubits can interact, causing irreversible decay of the quantum state. As a practical matter, however, there exists a high density of excitations out of the superconducting ground state even at ultralow temperature; these are known as quasiparticles. Observed quasiparticle densities are of order 1~$\mu$m$^{-3}$, tens of orders of magnitude larger than the equilibrium density expected from theory. Nonequilibrium quasiparticles extract energy from the qubit mode and induce discrete changes in qubit offset charge, a potential source of dephasing. Here we show that a dominant mechanism for quasiparticle poisoning in superconducting qubits is direct absorption of high-energy photons at the qubit junction. We use a Josephson junction-based photon source to controllably dose qubit circuits with millimeter-wave radiation, and we use an interferometric quantum gate sequence to reconstruct the charge parity on the qubit island. We find that the structure of the qubit itself acts as a resonant antenna for millimeter-wave radiation, providing an efficient path for photons to generate quasiparticle excitations. A deep understanding of this physics will pave the way to realization of next-generation superconducting qubits that are robust against quasiparticle poisoning and could enable a new class of quantum sensors for dark matter detection., Comment: 13 pages, 11 figures, 3 tables
Published: 2022

18. Comparison of methods for predicting COVID-19-related death in the general population using the OpenSAFELY platform

Author: OpenSAFELY Collaborative, Williamson, Elizabeth J, Tazare, John, Bhaskaran, Krishnan, McDonald, Helen I, Walker, Alex J, Tomlinson, Laurie, Wing, Kevin, Bacon, Sebastian, Bates, Chris, Curtis, Helen J, Forbes, Harriet J, Minassian, Caroline, Morton, Caroline E, Nightingale, Emily, Mehrkar, Amir, Evans, David, Nicholson, Brian D, Leon, David A, Inglesby, Peter, MacKenna, Brian, Davies, Nicholas G, DeVito, Nicholas J, Drysdale, Henry, Cockburn, Jonathan, Hulme, William J, Morley, Jessica, Douglas, Ian, Rentsch, Christopher T, Mathur, Rohini, Wong, Angel, Schultze, Anna, Croker, Richard, Parry, John, Hester, Frank, Harper, Sam, Grieve, Richard, Harrison, David A, Steyerberg, Ewout W, Eggo, Rosalind M, Diaz-Ordaz, Karla, Keogh, Ruth, Evans, Stephen JW, Smeeth, Liam, and Goldacre, Ben
Abstract: BACKGROUND: Obtaining accurate estimates of the risk of COVID-19-related death in the general population is challenging in the context of changing levels of circulating infection. METHODS: We propose a modelling approach to predict 28-day COVID-19-related death which explicitly accounts for COVID-19 infection prevalence using a series of sub-studies from new landmark times incorporating time-updating proxy measures of COVID-19 infection prevalence. This was compared with an approach ignoring infection prevalence. The target population was adults registered at a general practice in England in March 2020. The outcome was 28-day COVID-19-related death. Predictors included demographic characteristics and comorbidities. Three proxies of local infection prevalence were used: model-based estimates, rate of COVID-19-related attendances in emergency care, and rate of suspected COVID-19 cases in primary care. We used data within the TPP SystmOne electronic health record system linked to Office for National Statistics mortality data, using the OpenSAFELY platform, working on behalf of NHS England. Prediction models were developed in case-cohort samples with a 100-day follow-up. Validation was undertaken in 28-day cohorts from the target population. We considered predictive performance (discrimination and calibration) in geographical and temporal subsets of data not used in developing the risk prediction models. Simple models were contrasted to models including a full range of predictors. RESULTS: Prediction models were developed on 11,972,947 individuals, of whom 7999 experienced COVID-19-related death. All models discriminated well between individuals who did and did not experience the outcome, including simple models adjusting only for basic demographics and number of comorbidities: C-statistics 0.92-0.94. However, absolute risk estimates were substantially miscalibrated when infection prevalence was not explicitly modelled. CONCLUSIONS: Our proposed models allow absolute risk estimation in the context of changing infection prevalence but predictive performance is sensitive to the proxy for infection prevalence. Simple models can provide excellent discrimination and may simplify implementation of risk prediction tools.
Published: 2022

19. Assessing the Evolution and Impacts of Brazilian Hydropower

Author: Harrison, David
Subjects: Environmental Impact Assessment, Sustainable development, Hydropower, Brazil
Abstract: For over a century, hydropower has represented the largest source of Brazilian electricity, supplying more than three-quarters of power today. This paper traces Brazil’s reliance on hydropower over the 20th century alongside a growing concern for the impacts of industrialization on the environment, which culminated in the implementation of the Environmental Impact Assessment (EIA) in 1988. The adoption of the EIA was a defining moment for Brazilian environmental regulation. It required detailed analysis of proposed projects and allowed officials to make informed decisions regarding environmental and social impacts. This paper conducts a review of the EIA system, including both its global and Brazilian implementation, its influence on hydropower projects, and the fundamental challenges it faces as a regulatory tool. The theoretical evaluation of the EIA is expanded on through the comparison of Brazil’s largest Amazonian hydropower projects, the Tucuruí Dam, constructed before the EIA, and the Belo Monte Dam, constructed after. This comparative analysis demonstrates that the EIA has significantly altered the planning of hydropower dams, while also highlighting flaws in the EIA process that undermine its ability to mitigate environmental and social impacts. Although it is possible to reduce certain impacts associated with hydropower, this study suggests that issues such as deforestation, flooding, mass-displacement, loss of ecosystems, greenhouse gas emissions, and impacts on indigenous peoples are virtually unavoidable when constructing mega-dams within the Amazon region. These results recommend a renewed focus on alternative energy sources and necessitate careful consideration of hydropower’s role in Brazilian sustainable development.
Published: 2022
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20. Additional file 1 of Comparison of methods for predicting COVID-19-related death in the general population using the OpenSAFELY platform

Author: Williamson, Elizabeth J., Tazare, John, Bhaskaran, Krishnan, McDonald, Helen I., Walker, Alex J., Tomlinson, Laurie, Wing, Kevin, Bacon, Sebastian, Bates, Chris, Curtis, Helen J., Forbes, Harriet J., Minassian, Caroline, Morton, Caroline E., Nightingale, Emily, Mehrkar, Amir, Evans, David, Nicholson, Brian D., Leon, David A., Inglesby, Peter, MacKenna, Brian, Davies, Nicholas G., DeVito, Nicholas J., Drysdale, Henry, Cockburn, Jonathan, Hulme, William J., Morley, Jessica, Douglas, Ian, Rentsch, Christopher T., Mathur, Rohini, Wong, Angel, Schultze, Anna, Croker, Richard, Parry, John, Hester, Frank, Harper, Sam, Grieve, Richard, Harrison, David A., Steyerberg, Ewout W., Eggo, Rosalind M., Diaz-Ordaz, Karla, Keogh, Ruth, Evans, Stephen J. W., Smeeth, Liam, and Goldacre, Ben
Abstract: Additional file 1. Supplementary materials
Published: 2022
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21. The measurement of user benefits of urban transport projects : an analytical framework

Author: Harrison, David S.
Subjects: ComputingMilieux_COMPUTERSANDEDUCATION, ComputerApplications_COMPUTERSINOTHERSYSTEMS, Uncategorized
Abstract: This thesis was scanned from the print manuscript for digital preservation and is copyright the author. Researchers can access this thesis by asking their local university, institution or public library to make a request on their behalf. Monash staff and postgraduate students can use the link in the References field.
Published: 2022
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22. MultiPathGAN: Structure Preserving Stain Normalization using Unsupervised Multi-domain Adversarial Network with Perception Loss

Author: Nazki, Haseeb, Arandjelović, Ognjen, Um, InHwa, and Harrison, David
Subjects: FOS: Computer and information sciences, Computer Vision and Pattern Recognition (cs.CV), Image and Video Processing (eess.IV), Computer Science - Computer Vision and Pattern Recognition, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, FOS: Electrical engineering, electronic engineering, information engineering, Electrical Engineering and Systems Science - Image and Video Processing
Abstract: Histopathology relies on the analysis of microscopic tissue images to diagnose disease. A crucial part of tissue preparation is staining whereby a dye is used to make the salient tissue components more distinguishable. However, differences in laboratory protocols and scanning devices result in significant confounding appearance variation in the corresponding images. This variation increases both human error and the inter-rater variability, as well as hinders the performance of automatic or semi-automatic methods. In the present paper we introduce an unsupervised adversarial network to translate (and hence normalize) whole slide images across multiple data acquisition domains. Our key contributions are: (i) an adversarial architecture which learns across multiple domains with a single generator-discriminator network using an information flow branch which optimizes for perceptual loss, and (ii) the inclusion of an additional feature extraction network during training which guides the transformation network to keep all the structural features in the tissue image intact. We: (i) demonstrate the effectiveness of the proposed method firstly on H\&E slides of 120 cases of kidney cancer, as well as (ii) show the benefits of the approach on more general problems, such as flexible illumination based natural image enhancement and light source adaptation.
Published: 2022
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23. Realising the full potential of data-enabled trials in the UK: a call for action

Author: Sydes, Matthew R, Barbachano, Yolanda, Bowman, Louise, Denwood, Tom, Farmer, Andrew, Garfield-Birkbeck, Steph, Gibson, Martin, Gulliford, Martin C, Harrison, David A, Hewitt, Catherine, Logue, Jennifer, Navaie, Will, Norrie, John, O'Kane, Martin, Quint, Jennifer K, Rycroft-Malone, Jo, Sheffield, Jonathan, Smeeth, Liam, Sullivan, Frank, Tizzard, Juliet, Walker, Paula, Wilding, John, Williamson, Paula R, Landray, Martin, Morris, Andrew, Walker, Rhoswyn R, Williams, Hywel C, Valentine, Janet, Data Enabled Trials Group Workshop Group Members, Sydes, Matthew R [0000-0002-9323-1371], Bowman, Louise [0000-0003-1125-8616], Denwood, Tom [0000-0002-7337-2425], Farmer, Andrew [0000-0002-6170-4402], Garfield-Birkbeck, Steph [0000-0002-3181-2840], Gibson, Martin [0000-0002-1331-1524], Gulliford, Martin C [0000-0003-1898-9075], Harrison, David A [0000-0002-9002-9098], Hewitt, Catherine [0000-0002-0415-3536], Logue, Jennifer [0000-0001-9549-2738], Norrie, John [0000-0001-9823-9252], Quint, Jennifer K [0000-0003-0149-4869], Rycroft-Malone, Jo [0000-0003-3858-5625], Smeeth, Liam [0000-0002-9168-6022], Sullivan, Frank [0000-0002-6623-4964], Wilding, John [0000-0003-2839-8404], Williamson, Paula R [0000-0001-9802-6636], Landray, Martin [0000-0001-6646-827X], Morris, Andrew [0000-0002-1766-0473], Walker, Rhoswyn R [0000-0001-5605-2879], Williams, Hywel C [0000-0002-5646-3093], and Apollo - University of Cambridge Repository
Subjects: clinical trials, SARS-CoV-2, Patient Selection, statistics & research methods, COVID-19, Humans, health informatics, United Kingdom
Abstract: RATIONALE: Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up. APPROACH: The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for 'data-enabled clinical trials'. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation. REFLECTION: Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a 'route map' to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution. DISCUSSION: EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial's specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR's funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.
Published: 2021

24. Therapeutic targeting of inflammation in hypertension: from novel mechanisms to translational perspective

Author: Murray, Eleanor C., Nosalski, Ryszard, MacRitchie, Neil, Tomaszewski, Maciej, Maffia, Pasquale, Harrison, David G., and Guzik, Tomasz J.
Abstract: Animal models, human observational and genetic studies have shown that immune and inflammatory mechanisms play a key role in hypertension and its complications. We review the effects of immunomodulatory interventions on blood pressure, target organ damage and cardiovascular risk in humans. In experimental and small clinical studies both non-specific immunomodulatory approaches, such as mycophenolate mofetil and methotrexate, and medications targeting T and B lymphocytes, such as tacrolimus, cyclosporine, everolimus, rituximab, lower blood pressure and reduce organ damage. Mechanistically targeted immune interventions include isolevuglandin (isoLG) scavengers to prevent neo-antigen formation, co-stimulation blockade (abatacept, belatacept), and anti-cytokine therapies (secukinumab, tocilizumab, canakinumab, TNF-α inhibitors). In many studies, trial designs have been complicated by a lack of blood pressure related endpoints, inclusion of largely normotensive study populations, polypharmacy, and established comorbidities. Among a wide range of interventions reviewed, TNF-α inhibitors have provided the most robust evidence of blood pressure lowering. Treatment of periodontitis also appears to deliver non-pharmacological antihypertensive effects. Evidence of immunomodulatory drugs influencing hypertension-mediated organ damage are discussed. Animal model, observational studies, and trial data in humans support the therapeutic potential of immune targeted therapies in blood pressure lowering and in hypertension-mediated organ damage. Targeted studies are now needed to address their effects on blood pressure in hypertensive individuals.
Published: 2021

25. Guidelines for cellular and molecular pathology content in clinical trial protocols : the SPIRIT-Path extension

Author: Kendall, Timothy J, Robinson, Max, Brierley, Daniel J, Lim, Shujing Jane, O'Connor, Daniel J, Shaaban, Abeer M, Lewis, Ian, Chan, An-Wen, Harrison, David J, SPIRIT-Path group, University of St Andrews. School of Medicine, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, and University of St Andrews. Cellular Medicine Division
Subjects: medicine.medical_specialty, RM, Consensus, Delphi Technique, education, MEDLINE, Delphi method, E-NDAS, RC0254, Clinical Trial Protocols as Topic, SDG 3 - Good Health and Well-being, medicine, Humans, Medical physics, Pathology, Molecular, Protocol (science), Clinical Trials as Topic, Molecular pathology, business.industry, RC0254 Neoplasms. Tumors. Oncology (including Cancer), Digital pathology, Checklist, humanities, AC, RM Therapeutics. Pharmacology, Clinical trial, Oncology, Research Design, RB Pathology, Standard protocol, business, RB
Abstract: This Series paper was funded by the NCRI through the CMPath initiative. MS is supported by the Birmingham Cancer Research UK Centre (C17422/A25154). The SPIRIT-Path project is part of the NCRI CMPath initiative and is funded by Blood Cancer UK, Breast Cancer Now, Cancer Research UK, Chief Scientist Office (Scotland), Department of Health and Social Care (England), Health and Care Research Wales, Public Health Agency (Northern Ireland), Medical Research Council, Prostate Cancer UK, and the Tenovus Cancer Care. The 2013 SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) Statement provides evidence-based recommendations for the minimum content to be included in a clinical trial protocol. Assessment of biospecimens is often required for trial eligibility or as part of an outcome evaluation, and precision molecular approaches are increasingly used in trial design. However, cellular and molecular pathology practices within trials have not been codified or formalised. We developed international consensus reporting guidelines for cellular and molecular pathology content in clinical trial protocols (the SPIRIT-Path extension) using an international Delphi process, which assesses candidate items generated from a previous systematic review, followed by an expert consensus meeting. 74 individuals from five continents responded, including clinicians, statisticians, laboratory scientists, patient advocates, funders, industry representatives, journal editors, and regulators. The SPIRIT-Path guidelines recommend 14 additional items (seven extensions to the SPIRIT checklist and seven elaborations) that should be addressed in trial protocols containing pathology content, alongside the SPIRIT 2013 Statement items. SPIRIT-Path recommends that protocols should document the individuals, processes, and standards for all cellular and molecular pathology components of the trial, including all stages of the specimen pathway and any digital pathology methods, with specific consideration of the value of trial data and biological tissues for additional translational studies. Postprint
Published: 2021
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26. Rapamycin-mediated mouse lifespan extension: Late-life dosage regimes with sex-specific effects

Author: Strong, Randy, Miller, Richard A, Bogue, Molly, Fernandez, Elizabeth, Javors, Martin A, Libert, Sergiy, Marinez, Paul Anthony, Murphy, Michael P, Musi, Nicolas, Nelson, James F, Petrascheck, Michael, Reifsnyder, Peter, Richardson, Arlan, Salmon, Adam B, Macchiarini, Francesca, Harrison, David E, Strong, Randy [0000-0001-6643-3288], Miller, Richard A [0000-0001-9266-9649], Reifsnyder, Peter [0000-0001-5666-8040], Harrison, David E [0000-0003-2298-0954], and Apollo - University of Cambridge Repository
Subjects: Male, Sirolimus, β-GPA, Antibiotics, Antineoplastic, rapamycin, Longevity, MitoQ, survival, Mice, minocycline, Sex Factors, 17-DMAG, Animals, Female
Abstract: To see if variations in timing of rapamycin (Rapa), administered to middle aged mice starting at 20 months, would lead to different survival outcomes, we compared three dosing regimens. Initiation of Rapa at 42 ppm increased survival significantly in both male and female mice. Exposure to Rapa for a 3-month period led to significant longevity benefit in males only. Protocols in which each month of Rapa treatment was followed by a month without Rapa exposure were also effective in both sexes, though this approach was less effective than continuous exposure in female mice. Interpretation of these results is made more complicated by unanticipated variation in patterns of weight gain, prior to the initiation of the Rapa treatment, presumably due to the use of drug-free food from two different suppliers. The experimental design included tests of four other drugs, minocycline, β-guanidinopropionic acid, MitoQ, and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), but none of these led to a change in survival in either sex.
Published: 2020

27. Mitochondrial physiology: Gnaiger Erich et al ― MitoEAGLE Task Group

Author: Gnaiger, Erich, Aasander Frostner, Eleonor, Abdul Karim, Norwahidah, Abdel-Rahman, Engy Ali, Abumrad, Nada A, Acuna-Castroviejo, Dario, Adiele, Reginald C, Ahn, Bumsoo, Alencar, MB, Ali, Sameh S, Almeida, Angeles, Alton, Lesley, Alves, Marco G, Amati, Francesca, Amoedo, Nivea Dias, Amorim, Ricardo, Anderson, Ethan J, Andreadou, Ioanna, Antunes, Diana, Arago, Marc, Aral, Cenk, Arandarcikaite, Odeta, Arias-Reyes, Christian, Armand, Anne-Sophie, Arnould, Thierry, Avram, Vlad Florian, Axelrod, Christopher L, Bairam, Aida, Bailey, Damian M, Bajpeyi, Sudip, Bajzikova, Martina, Bakker, Barbara M, Barlow, Jonathan, Bardal, Tora, Banni, A, Bastos Sant'Anna Silva, Ana Carolina, Batterson, Philip, Battino, Maurizio, Bazil, Jason, Beard, Daniel A, Beleza, Jorge, Bednarczyk, Piotr, Bello, Fiona, Ben-Shachar, Dorit, Bento Guida, Jose Freitas, Bergdahl, Andreas, Berge, Rolf K, Bergmeister, Lisa, Bernardi, Paolo, Berridge, Michael V, Bettinazzi, Stefano, Bishop, David, Blier, Pierre U, Blindheim, Dan Filip, Boardman, Neoma T, Boetker, Hans Erik, Borchard, Sabine, Boros, Mihaly, Borsheim, Elisabet, Borras, Consuelo, Borutaite, Vilma, Botella, Javier, Bouillaud, Frederic, Bouitbir, Jamal, Boushel, Robert C, Bovard, Josh, Bravo-Sagua, Roberto, Breton, Sophie, Brown, David A, Brown, Guy C, Brown, Robert A, Brozinick, Joseph T, Buettner, Garry R, Burtscher, Johannes, Bustos, Matilde, Calabria, Elisa, Calbet, Jose A, Calzia, Enrico, Cannon, Daniel T, Cano Sanchez, Maria, Canto Alvarez, Carles, Cardinale, D, Cardoso, Luiza Helena Daltro, Carvalho, Eugenia, Casado Pinna, Marta, Cassar, Samantha, Castelo, Maria P, Castilho, Roger F, Cavalcanti-de-Albuquerque, Joao Paulo, Cecatto, Cristiane, Celen, Murat C, Cervinkova, Zuzana, Chabi, Beatrice, Chakrabarti, Lisa, Chakrabarti, Sasanka, Chaurasia, Bhagirath, Chen, Quan, Chicco, Adam J, Chinopoulos, Christos, Chowdhury, Subir K, Cizmarova, Beata, Clementi, Emilio, Coen, Paul M, Cohen, Bruce H, Coker, Robert H, Collin-Chenot, Anne, Coughlan, Melinda T, Coxito, Petro, Crisostomo, Luis, Crispim, Marcell, Crossland, Hannah, Dahdah, Norma, Dalgaard, Louise T, Dambrova, Maija, Danhelovska, Tereza, Darveau, Charles A, Darwin, Paula M, Das, Anibh M, Dash, Ranjan K, Davidova, Eliska, Davis, Michael S, Dayanidhi, Sudarshan, De Bem, Andreza Fabro, De Goede, Paul, De Palma, Clara, De Pinto, Vito, Dela, F, Dembinska-Kiec, Aldona, Detraux, Damien, Devaux, Yvan, Di Marcello, Marco, Di Paola, Floriana Jessica, Dias, Candida, Dias, Tania R, Diederich, Marc, Distefano, Giovanna, Djafarzadeh, Siamak, Doermann, Niklas, Doerrier, Carolina, Dong, Lan-Feng, Donnelly, Chris, Drahota, Zdenek, Duarte, Filipe Valente, Dubouchaud, Herve, Duchen, Michael R, Dumas, Jean-Francois, Durham, William J, Dymkowska, Dorota, Dyrstad, Sissel E, Dyson, Alex, Dzialowski, Edward M, Eaton, Simon, Ehinger, Johannes, Elmer, Eskil, Endlicher, Rene, Engin, Ayse B, Escames, Germaine, Evinova, Andrea, Ezrova, Zuzana, Falk, Marni Joy, Fell, David A, Ferdinandy, Peter, Ferko, Miroslav, Fernandez-Ortiz, Marisol, Erika, Fernandez-Vizarra, Ferreira, Julio Cesar Batista, Ferreira, Rita, Ferri, Alessandra, Festuccia, WT, Fessel, Joshua P, Filipovska, Aleksandra, Fisar, Zdenek, Fischer, Christine, Fischer, Michael, Fisher, Gordon, Fisher, Joshua J, Fontanesi, Flavia, Forbes-Hernandez, Tamara Y, Ford, Ellen, Fornaro, Mara, Fuertes Agudo, Marina, Fulton, Montana, Galina, Antonio, Galkin, Alexander, Gallee, Leon, Galli, Gina L, Gama Perez, Pau, Gan, Zhenji, Ganetzky, Rebecca, Gao, Yun, Garcia, Geovana S, Garcia-Rivas, Gerardo, Garcia-Roves, Pablo Miguel, Garcia-Souza, Luiz Felipe, Garlid, Keith D, Garrabou, Gloria, Garten, Antje, Gastaldelli, Amalia, Gayen, Jiaur, Genders, Amanda J, Genova, Maria Luisa, Giampieri, Francesca, Glatz, Jan FC, Giovarelli, Matteo, Goikoetxea Usandizaga, Naroa, Goncalo Teixeira da Silva, Rui, Goncalves, Debora Farina, Gonzalez-Armenta, Jenny L, Gonzalez-Francesqua, A, Gonzalez-Freire, Marta, Gonzalo, Hugo, Goodpaster, Bret H, Gorr, Thomas A, Gourlay, Campbell W, Grams, Bente, Granata, Cesare, Grefte, Sander, Grilo, Luis, Guarch, Meritxell Espino, Gueguen, Naig, Gumeni, Sentiljana, Haas, Clarissa B, Haavik, Jan, Hachmo, Yafit, Haendeler, Judith, Haider, Markus, Hajrulahovic, Anesa, Hamann, Andrea, Han, Jin, Han, Woo Hyun, Hancock, Chad R, Hand, Steven C, Handl, Jiri, Hansikova, Hana, Hardee, Justin P, Hargreaves, Ian P, Harper, Mary Ellen, Harrison, David K, Hassan, Hazirah, Hatakova, Zuzana, Hausenloy, Derek J, Heales, Simon JR, Heiestad, Christina, Hellgren, Kim T, Henrique, Alexandrino, Hepple, Russell T, Hernansanz-Agustin, Pablo, Hewakapuge, Sudinna, Hickey, Anthony J, Ho, Dieu Hien, Hoehn, Kyle L, Hoel, Frederik, Holland, Olivia J, Holloway, Graham P, Holzner, Lorenz, Hoppel, Charles L, Hoppeler, H, Hoppel, Florian, Houstek, Josef, Huete-Ortega, Maria, Hyrossova, Petra, Iglesias-Gonzalez, Javier, Indiveri, Cesare, Irving, Brian A, Isola, Raffaella, Iyer, Shilpa, Jackson, Christophe B, Jadiya, Pooja, Jana, Prado Fabian, Jandeleit-Dahm, K, Jang, David H, Jang, Young C, Janowska, Joanna, Jansen, Kirsten, Jansen-Duerr, Pidder, Jansone, Baiba, Jarmuszkiewicz, Wieslawa, Jaskiewicz, Anna, Jaspers, Richard T, Jedlicka, Jan, Jerome, Estaquier, Jespersen, Nichlas R, Jha, Rajan K, Joseph, Vincent, Juhasz, Laszlo, Jurczak, Michael J, Jurk, Diana, Kaambre, Tuuli, Kaczor, Jan J, Kainulainen, Heikki, Kampa, Rafal Pawel, Kandel, Sunil M, Kane, Daniel A, Kapferer, Werner, Kapnick, Senta, Kappler, Lisa, Karabatsiakis, Alexander, Karavaeva, Iuliia, Karkucinska-Wieckowska, Agnieszka, Kaur, Sarbjot, Keijer, Jaap, Keller, Markus A, Keppner, Gloria, Khamoui, Andy V, Kidere, Dita, Kilbaugh, Todd, Kim, Hyoung Kyu, Kim, Julian KS, Kimoloi, Sammy, Klepinin, Aleksandr, Klepinina, Lyudmila, Klingenspor, Martin, Klocker, Helmut, Komlódi, Timea, Kolasa, Iris, Koopman, Werner JH, Kopitar-Jerala, Natasa, Kowaltowski, Alicia J, Kozlov, Andrey V, Krajcova, Adela, Krako Jakovljevic, Nina, Kristal, Bruce S, Krycer, Jamer R, Kuang, Jujiao, Kucera, Otto, Kuka, Janis, Kwak, Hyo Bum, Kwast, Kurt, Kwon, Oh Sung, Laasmaa, Martin, Labieniec-Watala, Magdalena, Lai, Nicola, Lalic, Nebojsa M, Land, John M, Lane, Nick, Laner, Verena, Lanza, Ian R, Laouafa, Sofien, Larsen, Steen, Larsen, Terje S, Lavery, Gareth G, Lazou, Antigone, Ledo, Ana Margarida, Lee, Hong Kyu, Leeuwenburgh, Christiaan, Lehti, Maarit, Lemieux, Helene, Lenaz, Giorgio, Lerfall, Jorgen, Li, Pingan A, Li Puma, Lance, Liang, Liping, Liepins, Edgars, Lin, Chien-Te, Liu, Jiankang, Lopez, Luis C, Lucchinetti, Eliana, Ma, Tao, Macedo, Maria P, Machado, Ivo F, Maciej, Sarah, MacMillan-Crow, Lee Ann, Magalhaes, Jose, Magri, Andrea, Majtnerova, Pavlina, Makarova, Elina, Makrecka-Kuka, Marina, Malik, Afshan N, Marcouiller, Francois, Marechal, Amandine, Markova, Michaela, Markovic, Ivanka, Martin, Daniel S, Martins, Ana Dias, Martins, Joao D, Maseko, Tumisang Edward, Maull, Felicia, Mazat, Jean Pierre, McKenna, Helen T, McKenzie, Matthew, McMillan, Duncan GG, McStay, Gavin P, Menze, Michael A, Mendham, Amy, Mercer, John R, Merz, Tamara, Messina, Angela, Meszaros, Andras T, Methner, Axel, Michalak, Slawomir, Mila Guasch, Maria, Minuzzi, Luciele M, Misirkic Marjanovic, Maja, Moellering, Douglas R, Moisoi, Nicoleta, Molina, Anthony JA, Montaigne, David, Moore, Anthony L, Moore, Christy, Moreau, Kerrie, Moreira, Bruno P, Moreno-Sanchez, Rafael, Mracek, Tomas, Muccini, Anna Maria, Muntane, Jordi, Muntean, Danina M, Murray, Andrew J, Musiol, Eva, Nabben, Miranda, Nair, K Sreekumaran, Nehlin, Jan O, Nemec, Michal, Nesci, Salvatore, Neufer, P Darrell, Neuzil, Jiri, Neviere, Remi, Newsom, Sean A., Norman, Jennifer, Nozickova, Katerina, Nunes, Sara, Nuoffer, Jean-Marc, O'Brien, Kristin, O'Brien, Katie A, O'Gorman, Donal, Olgar, Yusuf, Oliveira, Ben, Oliveira, Jorge, Oliveira, Marcus F, Oliveira, Marcos Tulio, Oliveira, Pedro F, Oliveira, Paulo J, Olsen, Rolf Erik, Orynbayeva, Zulfiya, Osiewacz, Heinz D, Paez, Hector, Pak, Youngmi K, Pallotta, Maria L, Palmeira, Carlos M, Parajuli, Nirmala, Passos, Joao F, Passrugger, Manuela, Patel, Hemal H, Pavlova, Nadia, Pavlovic, Kasja, Pecina, Petr, Pedersen, Tina M, Perales, Jose Carlos, Pereira da Silva Grilo da Silva, Filomena, Pereira, Rita, Perez Valencia, Juan A, Perks, Kara L, Pesta, Dominik, Petit, Patrice X, Pettersen Nitschke, Ina Katrine, Pichaud, Nicolas, Pichler, Irene, Piel, Sarah, Pietka, Terri A, Pinho, Sonia A, Pino, Maria F, Pirkmajer, Sergej, Place, Nicolas, Plangger, Mario, Porter, Craig, Porter, Richard K, Preguica, Ines, Procaccio, Vincent, Prochownik, Edward V, Prola, Alexandre, Pulinilkunnil, Thomas, Puskarich, Michael A, Puurand, Marju, Radenkovic, Filip, Ramzan, Rabia, Rattan, Suresh IS, Reano, Simone, Reboredo, Patricia, Rees, Bernard B, Renner-Sattler, Kathrin, Rial, Eduardo, Robinson, Matthew M, Roden, Michael, Rodrigues, Ana Sofia, Rodriguez, Enrique, Rodriguez-Enriquez, Sara, Roesland, Gro Vatne, Rolo, Anabela Pinto, Ropelle, Eduardo R, Roshanravan, Baback, Rossignol, Rodrigue, Rossiter, Harry B, Rousar, Tomas, Rubelj, Ivica, Rybacka-Mossakowska, Joanna, Saada, Ann, Safaei, Zahra, Sarlak, Saharnaz, Salin, Karine, Salvadego, Desy, Sandi, Carmen, Saner, Nicholas, Santos, Diana, Sanz, Alberto, Sardao, Vilma, Sazanov, Leonid A, Scaife, Paula, Scatena, Roberto, Schartner, Melanie, Scheibye-Knudsen, Morten, Schilling, Jan M, Schlattner, Uwe, Schmitt, Sabine, Schneider Gasser, Edith Mariane, Schoenfeld, Peter, Schots, Pauke C, Schulz, Rainer, Schwarzer, Christoph, Scott, Graham R, Selman, Colin, Sendon, Pamella Marie, Shabalina, Irina G, Sharma, Pushpa, Sharma, Vipin, Shevchuk, Igor, Shirazi, Reza, Shiroma, Jonathan G, Siewiera, Karolina, Silber, Ariel M, Silva, Ana Maria, Sims, Carrie A, Singer, Dominique, Singh, Brijesh Kumar, Skolik, Robert A, Smenes, Benedikte Therese, Smith, James, Soares, Félix Alexandre Antunes, Sobotka, Ondrej, Sokolova, Inna, Solesio Torregrosa, M De la Encarnacion, Soliz, Jorge, Sonkar, Vijay K, Sova, Marina, Sowton, Alice P, Sparagna, Genevieve C, Sparks, Lauren M, Spinazzi, Marco, Stankova, Pavla, Starr, Jonathan, Stary, Creed, Stefan, Eduard, Stelfa, Gundega, Stepto, Nigel K, Stevanovic, Jelena, Stiban, Johnny, Stier, Antoine, Stocker, Roland, Storder, Julie, Sumbalova, Zuzana, Suomalainen, Wartiovaara Anu, Suravajhala, Prashanth, Svalbe, Baiba, Swerdlow, Russel H, Swiniuch, Daria, Szabo, Ildiko, Szewczyk, Adam, Szibor, Marten, Tanaka, Masashi, Tandler, Bernard, Tarnopolsky, Mark A, Tausan, Daniel, Tavernarakis, Nektarios, Tepp, Kersti, Teodoro, J, Thakkar, Himani, Thapa, Maheshwo, Thyfault, John P, Tomar, Dhanendra, Ton, Riccardo, Torp, May-Kristin, Torres-Quesada, Omar, Towheed, Atif, Treberg, Jason R, Tretter, Laszlo, Trewin, Adam J, Trifunovic, Aleksandra, Trivigno, Catherine, Tronstad, Karl Johan, Trougakos, Ioannis P, Truu, Laura, Tuncay, Erkan, Turan, Belma, Tyrrell, Daniel J, Urban, Tomas, Urner, Sofia, Valentine, Joseph Marco, Van Bergen, Nicole J, Van der Ende, Miranda, Varricchio, Frederick, Vaupel, Peter, Vella, Joanna, Vendelin, Marko, Verdaguer, IB, Vercesi, Anibal E, Vernerova, Andrea, Victor, Victor Manuel, Vieira Ligo Teixeira, Camila, Vidimce, Josif, Viel, Christian, Vieyra, Adalberto, Vilks, Karlis, Villena, Joseph A, Vincent, Vinnyfred, Vinogradov, Andrey D, Viscomi, Carlo, Vitorino, Rui Miguel Pinheiro, Vlachaki Walker, Julia, Vogt, Sebastian, Volani, Chiara, Volska, Kristine, Votion, Dominique-Marie, Vujacic-Mirski, Ksenija, Wagner, Brett A, Ward, Marie Louise, Warnsmann, Verena, Wasserman, David H, Watala, Cezary, Wei, Yau-Huei, Weinberger, Klaus M, White, Sarah, Whitfield, Jamie, Wickert, Anika, Wieckowski, Mariusz R, Wiesner, Rudolf J, Williams, Caroline M, Winwood-Smith, Hugh, Wohlgemuth, Stephanie E, Wohlwend, Martin, Wolff, Jonci Nikolai, Wrutniak-Cabello, Chantal, Wuest, Rob C I, Yokota, Takashi, Zablocki, Krzysztof, Zanon, Alessandra, Zanou, Nadege, Zaugg, Kathrin, Zaugg, Michael, Zdrazilova, Lucie, Zhang, Yong, Zhang, Yi Zhu, Zikova, Alena, Zischka, Hans, Zorzano, Antonio, Zujovic, Tijana, Zurmanova, Jitka, Zvejniece, Liga, Lagarrigue, Sylviane, Munro, Daniel, Pereira, Susana, Laranjinha, Joäo, Hecker, Matthias, Jusic, Amela, Prigione, Alessandro, Sommer, Natascha, Weissig, Volkmar, Guida, Bento, G, John G, Jones, JG, AMS - Tissue Function & Regeneration, AMS - Rehabilitation & Development, Physiology, Mito-Eagle - Evolution-Age-Gender-Lifestyle-Environment (Mito-Eagle), Oroboros Instruments, Dynamique Musculaire et Métabolisme (DMEM), Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Gnaiger Erich, Aasander Frostner Eleonor, Abdul Karim Norwahidah, Abdel-Rahman Engy Ali, Abumrad Nada A, Acuna-Castroviejo Dario, Adiele Reginald C, Ahn Bumsoo, Alencar Mayke Bezerra, Ali Sameh S, Almeida Angeles, Alton Lesley, Alves Marco G, Amati Francesca, Amoedo Nivea Dias, Amorim Ricardo, Anderson Ethan J, Andreadou Ioanna, Antunes Diana, Arago Marc, Aral Cenk, Arandarcikaite Odeta, Arias-Reyes Christian, Armand Anne-Sophie, Arnould Thierry, Avram Vlad F, Axelrod Christopher L, Bailey Damian M, Bairam Aida, Bajpeyi Sudip, Bajzikova Martina, Bakker Barbara M, Banni Aml, Bardal Tora, Barlow J, Bastos Sant'Anna Silva Ana Carolina, Batterson Philip M, Battino Maurizio, Bazil Jason N, Beard Daniel A, Bednarczyk Piotr, Beleza Jorge, Bello Fiona, Ben-Shachar Dorit, Bento Guida Jose Freitas, Bergdahl Andreas, Berge Rolf K, Bergmeister Lisa, Bernardi Paolo, Berridge Michael V, Bettinazzi Stefano, Bishop David J, Blier Pierre U, Blindheim Dan Filip, Boardman Neoma T, Boetker Hans Erik, Borchard Sabine, Boros Mihaly, Boersheim Elisabet, Borras Consuelo, Borutaite Vilma, Botella Javier, Bouillaud Frederic, Bouitbir Jamal, Boushel Robert C, Bovard Josh, Bravo-Sagua Roberto, Breton Sophie, Brown David A, Brown Guy C, Brown Robert Andrew, Brozinick Joseph T, Buettner Garry R, Burtscher Johannes, Bustos Matilde, Calabria Elisa, Calbet Jose AL, Calzia Enrico, Cannon Daniel T, Cano Sanchez Maria Consolacion, Canto Alvarez Carles, Cardinale Daniele A, Cardoso Luiza HD, Carvalho Eugenia, Casado Pinna Marta, Cassar Samantha, Castelo Rueda Maria Paulina, Castilho Roger F, Cavalcanti-de-Albuquerque Joao Paulo, Cecatto Cristiane, Celen Murat C, Cervinkova Zuzana, Chabi Beatrice, Chakrabarti Lisa, Chakrabarti Sasanka, Chaurasia Bhagirath, Chen Quan, Chicco Adam J, Chinopoulos Christos, Chowdhury Subir Kumar, Cizmarova Beata, Clementi Emilio, Coen Paul M, Cohen Bruce H, Coker Robert H, Collin-Chenot Anne, Coughlan Melinda T, Coxito Pedro, Crisostomo Luis, Crispim Marcell, Crossland Hannah, Dahdah Norma Ramon, Dalgaard Louise T, Dambrova Maija, Danhelovska Tereza, Darveau Charles-A, Darwin Paula M, Das Anibh Martin, Dash Ranjan K, Davidova Eliska, Davis Michael S, Dayanidhi Sudarshan, De Bem Andreza Fabro, De Goede Paul, De Palma Clara, De Pinto Vito, Dela Flemming, Dembinska-Kiec Aldona, Detraux Damian, Devaux Yvan, Di Marcello Marco, Di Paola Floriana Jessica, Dias Candida, Dias Tania R, Diederich Marc, Distefano Giovanna, Djafarzadeh Siamak, Doermann Niklas, Doerrier Carolina, Dong Lan-Feng, Donnelly Chris, Drahota Zdenek, Duarte Filipe Valente, Dubouchaud Herve, Duchen Michael R, Dumas Jean-Francois, Durham William J, Dymkowska Dorota, Dyrstad Sissel E, Dyson Alex, Dzialowski Edward M, Eaton Simon, Ehinger Johannes K, Elmer Eskil, Endlicher Rene, Engin Ayse Basak, Escames Germaine, Evinova Andrea, Ezrova Zuzana, Falk Marni J, Fell David A, Ferdinandy Peter, Ferko Miroslav, Fernandez-Ortiz Marisol, Fernandez-Vizarra Erika, Ferreira Julio Cesar B, Ferreira Rita Maria P, Ferri Alessandra, Fessel Joshua Patrick, Festuccia William T, Filipovska Aleksandra, Fisar Zdenek, Fischer Christine, Fischer Michael J, Fisher Gordon, Fisher Joshua J, Fontanesi Flavia, Forbes-Hernandez Tamara Y, Ford Ellen, Fornaro Mara, Fuertes Agudo Marina, Fulton Montana, Galina Antonio, Galkin Alexander, Gallee Leon, Galli Gina L J, Gama Perez Pau, Gan Zhenji, Ganetzky Rebecca, Gao Yun, Garcia Geovana S, Garcia-Rivas Gerardo, Garcia-Roves Pablo Miguel, Garcia-Souza Luiz F, Garlid Keith D, Garrabou Gloria, Garten Antje, Gastaldelli Amalia, Gayen Jiaur, Genders Amanda J, Genova Maria Luisa, Giampieri Francesca, Giovarelli Matteo, Glatz Jan FC, Goikoetxea Usandizaga Naroa, Goncalo Teixeira da Silva Rui, Goncalves Debora Farina, Gonzalez- Armenta Jenny L, Gonzalez-Franquesa Alba, Gonzalez-Freire Marta, Gonzalo Hugo, Goodpaster Bret H, Gorr Thomas A, Gourlay Campbell W, Grams Bente, Granata Cesare, Grefte Sander, Grilo Luis, Guarch Meritxell Espino, Gueguen Naig, Gumeni Sentiljana, Haas Clarissa, Haavik Jan, Hachmo Yafit, Haendeler Judith, Haider Markus, Hajrulahovic Anesa, Hamann Andrea, Han Jin, Han Woo Hyun, Hancock Chad R, Hand Steven C, Handl Jiri, Hansikova Hana, Hardee Justin P, Hargreaves Iain P, Harper Mary- Ellen, Harrison David K, Hassan Hazirah, Hatokova Zuzana, Hausenloy Derek J, Heales Simon JR, Hecker Matthias, Heiestad Christina, Hellgren Kim T, Henrique Alexandrino, Hepple Russell T, Hernansanz- Agustin Pablo, Hewakapuge Sudinna, Hickey Anthony J, Ho Dieu Hien, Hoehn Kyle L, Hoel Fredrik, Holland Olivia J, Holloway Graham P, Holzner Lorenz, Hoppel Charles L, Hoppel Florian, Hoppeler Hans, Houstek Josef, Huete-Ortega Maria, Hyrossova Petra, Iglesias-Gonzalez Javier, Indiveri Cesare, Irving Brian A, Isola Raffaella, Iyer Shilpa, Jackson Christopher Benjamin, Jadiya Pooja, Jana Prado Fabian, Jandeleit-Dahm Karin, Jang David H, Jang Young Charles, Janowska Joanna, Jansen Kirsten M, Jansen-Duerr Pidder, Jansone Baiba, Jarmuszkiewicz Wieslawa, Jaskiewicz Anna, Jaspers Richard T, Jedlicka Jan, Jerome Estaquier, Jespersen Nichlas Riise, Jha Rajan Kumar, Jones John G, Joseph Vincent, Juhasz Laszlo, Jurczak Michael J, Jurk Diana, Jusic Amela, Kaambre Tuuli, Kaczor Jan Jacek, Kainulainen Heikki, Kampa Rafal Pawel, Kandel Sunil Mani, Kane Daniel A, Kapferer Werner, Kapnick Senta, Kappler Lisa, Karabatsiakis Alexander, Karavaeva Iuliia, Karkucinska-Wieckowska Agnieszka, Kaur Sarbjot, Keijer Jaap, Keller Markus A, Keppner Gloria, Khamoui Andy V, Kidere Dita, Kilbaugh Todd, Kim Hyoung Kyu, Kim Julian KS, Kimoloi Sammy, Klepinin Aleksandr, Klepinina Lyudmila, Klingenspor Martin, Klocker Helmut, Kolassa Iris, Komlodi Timea, Koopman Werner JH, Kopitar-Jerala Natasa, Kowaltowski Alicia J, Kozlov Andrey V, Krajcova Adela, Krako Jakovljevic Nina, Kristal Bruce S, Krycer James R, Kuang Jujiao, Kucera Otto, Kuka Janis, Kwak Hyo Bum, Kwast Kurt E, Kwon Oh Sung, Laasmaa Martin, Labieniec-Watala Magdalena, Lagarrigue Sylviane, Lai Nicola, Lalic Nebojsa M, Land John M, Lane Nick, Laner Verena, Lanza Ian R, Laouafa Sofien, Laranjinha Joao, Larsen Steen, Larsen Terje S, Lavery Gareth G, Lazou Antigone, Ledo Ana Margarida, Lee Hong Kyu, Leeuwenburgh Christiaan, Lehti Maarit, Lemieux Helene, Lenaz Giorgio, Lerfall Joergen, Li Pingan Andy, Li Puma Lance, Liang Liping, Liepins Edgars, Lin Chien-Te, Liu Jiankang, Lopez Garcia Luis Carlos, Lucchinetti Eliana, Ma Tao, Macedo Maria Paula, Machado Ivo F, Maciej Sarah, MacMillan-Crow Lee Ann, Magalhaes Jose, Magri Andrea, Majtnerova Pavlina, Makarova Elina, Makrecka-Kuka Marina, Malik Afshan N, Marcouiller Francois, Marechal Amandine, Markova Michaela, Markovic Ivanka, Martin Daniel S, Martins Ana Dias, Martins Joao D, Maseko Tumisang Edward, Maull Felicia, Mazat Jean-Pierre, McKenna Helen T, McKenzie Matthew, McMillan Duncan GG, McStay Gavin P, Mendham Amy, Menze Michael A, Mercer John R, Merz Tamara, Messina Angela, Meszaros Andras, Methner Axel, Michalak Slawomir, Mila Guasch Maria, Minuzzi Luciele M, Misirkic Marjanovic Maja, Moellering Douglas R, Moisoi Nicoleta, Molina Anthony JA, Montaigne David, Moore Anthony L, Moore Christy, Moreau Kerrie, Moreira Bruno P, Moreno-Sanchez Rafael, Mracek Tomas, Muccini Anna Maria, Munro Daniel, Muntane Jordi, Muntean Danina M, Murray Andrew James, Musiol Eva, Nabben Miranda, Nair K Sreekumaran, Nehlin Jan O, Nemec Michal, Nesci Salvatore, Neufer P Darrell, Neuzil Jiri, Neviere Remi, Newsom Sean A, Norman Jennifer, Nozickova Katerina, Nunes Sara, Nuoffer Jean-Marc, O'Brien Kristin, O'Brien Katie A, O'Gorman Donal, Olgar Yusuf, Oliveira Ben, Oliveira Jorge, Oliveira Marcus F, Oliveira Marcos Tulio, Oliveira Pedro Fontes, Oliveira Paulo J, Olsen Rolf Erik, Orynbayeva Zulfiya, Osiewacz Heinz D, Paez Hector, Pak Youngmi Kim, Pallotta Maria Luigia, Palmeira Carlos, Parajuli Nirmala, Passos Joao F, Passrugger Manuela, Patel Hemal H, Pavlova Nadia, Pavlovic Kasja, Pecina Petr, Pedersen Tina M, Perales Jose Carles, Pereira da Silva Grilo da Silva Filomena, Pereira Rita, Pereira Susana P, Perez Valencia Juan Alberto, Perks Kara L, Pesta Dominik, Petit Patrice X, Pettersen Nitschke Ina Katrine, Pichaud Nicolas, Pichler Irene, Piel Sarah, Pietka Terri A, Pinho Sonia A, Pino Maria F, Pirkmajer Sergej, Place Nicolas, Plangger Mario, Porter Craig, Porter Richard K, Preguica Ines, Prigione Alessandro, Procaccio Vincent, Prochownik Edward V, Prola Alexandre, Pulinilkunnil Thomas, Puskarich Michael A, Puurand Marju, Radenkovic Filip, Ramzan Rabia, Rattan Suresh IS, Reano Simone, Reboredo-Rodriguez Patricia, Rees Bernard B, Renner-Sattler Kathrin, Rial Eduardo, Robinson Matthew M, Roden Michael, Rodrigues Ana Sofia, Rodriguez Enrique, Rodriguez-Enriquez Sara, Roesland Gro Vatne, Rohlena Jakub, Rolo Anabela Pinto, Ropelle Eduardo R, Roshanravan Baback, Rossignol Rodrigue, Rossiter Harry B, Rousar Tomas, Rubelj Ivica, Rybacka-Mossakowska Joanna, Saada Reisch Ann, Safaei Zahra, Salin Karine, Salvadego Desy, Sandi Carmen, Saner Nicholas, Santos Diana, Sanz Alberto, Sardao Vilma, Sarlak Saharnaz, Sazanov Leonid A, Scaife Paula, Scatena Roberto, Schartner Melanie, Scheibye-Knudsen Morten, Schilling Jan M, Schlattner Uwe, Schmitt Sabine, Schneider Gasser Edith Mariane, Schoenfeld Peter, Schots Pauke C, Schulz Rainer, Schwarzer Christoph, Scott Graham R, Selman Colin, Sendon Pamella Marie, Shabalina Irina G, Sharma Pushpa, Sharma Vipin, Shevchuk Igor, Shirazi Reza, Shiroma Jonathan G, Siewiera Karolina, Silber Ariel M, Silva Ana Maria, Sims Carrie A, Singer Dominique, Singh Brijesh Kumar, Skolik Robert A, Smenes Benedikte Therese, Smith James, Soares Felix Alexandre Antunes, Sobotka Ondrej, Sokolova Inna, Solesio Maria E, Soliz Jorge, Sommer Natascha, Sonkar Vijay K, Sova Marina, Sowton Alice P, Sparagna Genevieve C, Sparks Lauren M, Spinazzi Marco, Stankova Pavla, Starr Jonathan, Stary Creed, Stefan Eduard, Stelfa Gundega, Stepto Nigel K, Stevanovic Jelena, Stiban Johnny, Stier Antoine, Stocker Roland, Storder Julie, Sumbalova Zuzana, Suomalainen Anu, Suravajhala Prashanth, Svalbe Baiba, Swerdlow Russell H, Swiniuch Daria, Szabo Ildiko, Szewczyk Adam, Szibor Marten, Tanaka Masashi, Tandler Bernard, Tarnopolsky Mark A, Tausan Daniel, Tavernarakis Nektarios, Teodoro Joao Soeiro, Tepp Kersti, Thakkar Himani, Thapa Maheshwor, Thyfault John P, Tomar Dhanendra, Ton Riccardo, Torp May-Kristin, Torres-Quesada Omar, Towheed Atif, Treberg Jason R, Tretter Laszlo, Trewin Adam J, Trifunovic Aleksandra, Trivigno Catherine, Tronstad Karl Johan, Trougakos Ioannis P, Truu Laura, Tuncay Erkan, Turan Belma, Tyrrell Daniel J, Urban Tomas, Urner Sofia, Valentine Joseph Marco, Van Bergen Nicole J, Van der Ende Miranda, Varricchio Frederick, Vaupel Peter, Vella Joanna, Vendelin Marko, Vercesi Anibal E, Verdaguer Ignasi Bofill, Vernerova Andrea, Victor Victor Manuel, Vieira Ligo Teixeira Camila, Vidimce Josif, Viel Christian, Vieyra Adalberto, Vilks Karlis, Villena Josep A, Vincent Vinnyfred, Vinogradov Andrey D, Viscomi Carlo, Vitorino Rui Miguel Pinheiro, Vlachaki Walker Julia, Vogt Sebastian, Volani Chiara, Volska Kristine, Votion Dominique-Marie, Vujacic-Mirski Ksenija, Wagner Brett A, Ward Marie Louise, Warnsmann Verena, Wasserman David H, Watala Cezary, Wei Yau-Huei, Weinberger Klaus M, Weissig Volkmar, White Sarah Haverty, Whitfield Jamie, Wickert Anika, Wieckowski Mariusz R, Wiesner Rudolf J, Williams Caroline M, Winwood-Smith Hugh, Wohlgemuth Stephanie E, Wohlwend Martin, Wolff Jonci Nikolai, Wrutniak-Cabello Chantal, Wuest Rob CI, Yokota Takashi, Zablocki Krzysztof, Zanon Alessandra, Zanou Nadege, Zaugg Kathrin, Zaugg Michael, Zdrazilova Lucie, Zhang Yong, Zhang Yizhu, Zikova Alena, Zischka Hans, Zorzano Antonio, Zujovic Tijana, Zurmanova Jitka, Zvejniece Liga
Subjects: uncoupling, MitoPedia: Respiratory states, SI - The International System of Units, IUPAC, Coupling control, Mitochondrial preparations, Protonmotive force, Uncoupling, Oxidative phosphorylation, Phosphorylation efficiency, Electron transfer-pathway, LEAK-respiration, Residual oxygen consumption, Normalization of rate, Flow, Flux, Flux control ratio, Mitochondrial marker, Cell count, Oxygen, [SDV]Life Sciences [q-bio], coupling control, protonmotive force, oxidative phosphorylation, mitochondrial respiratory control, State 4, electron transfer, State 2, State 3, Mitochondrial physiology, residual oxygen consumption, flux, normalization, ion leak and slip compensatory state, efficiency, electron transfer system, flow, mitochondrial physiology, oxygen, mitochondrial preparations, proton leak
Abstract: As the knowledge base and importance of mitochondrial physiology to evolution, health and diseaseexpands, the necessity for harmonizing the terminologyconcerning mitochondrial respiratory states and rates has become increasingly apparent. Thechemiosmotic theoryestablishes the mechanism of energy transformationandcoupling in oxidative phosphorylation. Theunifying concept of the protonmotive force providestheframeworkfordeveloping a consistent theoretical foundation ofmitochondrial physiology and bioenergetics.We followthe latest SI guidelines and those of the International Union of Pure and Applied Chemistry(IUPAC)onterminology inphysical chemistry, extended by considerationsofopen systems and thermodynamicsof irreversible processes.Theconcept-driven constructive terminology incorporates the meaning of each quantity and alignsconcepts and symbols withthe nomenclature of classicalbioenergetics. We endeavour to provide a balanced view ofmitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes.Uniform standards for evaluation of respiratory states and rates will ultimatelycontribute BEC 2020.1 doi:10.26124/bec:2020-0001.v1www.bioenergetics-communications.org3of 44to reproducibility between laboratories and thussupport the development of datarepositoriesof mitochondrial respiratory function in species, tissues, and cells.Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery.
Published: 2020
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28. WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies

Author: Warren, Anne Y, Harrison, David, Warren, Anne Y [0000-0002-1170-7867], Harrison, David [0000-0001-9041-9988], and Apollo - University of Cambridge Repository
Subjects: Nephrology, medicine.medical_specialty, Staging, Urology, Pathological staging, 030232 urology & nephrology, Review, urologic and male genital diseases, World Health Organization, 03 medical and health sciences, 0302 clinical medicine, Renal cell carcinoma, Internal medicine, Biopsy, medicine, Pathology, Humans, Grading (tumors), Pathological, Carcinoma, Renal Cell, Societies, Medical, Neoplasm Staging, Characteristic morphology, medicine.diagnostic_test, business.industry, Digital pathology, medicine.disease, Topic Paper, Kidney Neoplasms, Grading, 030220 oncology & carcinogenesis, Radiology, Neoplasm Grading, business
Abstract: PURPOSE: Pathological parameters assessed on biopsies and resection specimens have a pivotal role in the diagnosis, prognosis and management of patients with renal cell carcinoma (RCC). METHODS: A non-systematic literature search was performed, updated to January 2018, to identify key standards and controversies in the pathological classification, grading and staging of RCC. RESULTS: Although most RCCs exhibit characteristic morphology that enables easy categorisation, RCCs show considerable morphological heterogeneity and it is not uncommon for there to be difficulty in assigning a tumour type, especially with rarer tumour subtypes. The differentiation between benign and malignant oncocytic tumours remains a particular challenge. The development of additional immunohistochemical and molecular tests is needed to facilitate tumour typing, because of the prognostic and therapeutic implications, and to enable more reliable identification of poorly differentiated metastatic tumours as being of renal origin. Any new tests need to be applicable to small biopsy samples, to overcome the heterogeneity of renal tumours. There is also a need to facilitate identification of tumour types that have genetic implications, to allow referral and management at specialist centres. Digital pathology has a potential role in such referral practice. CONCLUSION: Much has been done to standardise pathological assessment of renal cell carcinomas in recent years, but there still remain areas of difficulty in classification and grading of these heterogeneous tumours.
Published: 2018

29. The novel nucleoside analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human Phase 1 clinical trial

Author: Schwenzer, Hagen, De Zan, Erica, Elshani, Mustafa, van Stiphout, Ruud, Kudsy, Mary, Morris, Josephine, Ferrari, Valentina, Um, In Hwa, Chettle, James, Kazmi, Farasat, Campo, Leticia, Easton, Alistair, Nijman, Sebastian, Serpi, Michaela, Symeonides, Stefan, Plummer, Ruth, Harrison, David J., Bond, Gareth, Blagden, Sarah P., University of St Andrews. School of Medicine, University of St Andrews. Cellular Medicine Division, and University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis
Subjects: RC0254, RM, fluids and secretions, SDG 3 - Good Health and Well-being, RC0254 Neoplasms. Tumors. Oncology (including Cancer), NDAS, QH426 Genetics, QH426, RM Therapeutics. Pharmacology
Abstract: We thank the Oxford Genomics Centre at the Wellcome Centre for Human Genetics (funded by Wellcome Trust grant reference 203141/Z/16/Z) for the generation and initial processing of the sequencing data. This work was funded in part by NuCana plc. The Oxford Early Phase Clinical Trials Unit, the Edinburgh and Newcastle Trials units are grateful for support from CRUK and Experimental Cancer Medicine Centre (ECMC) funding. Purpose: Nucleoside analogues form the backbone of many therapeutic regimens in oncology and require the presence of intracellular enzymes for their activation. A ProTide is comprised of a nucleoside fused to a protective phosphoramidate cap. ProTides are easily incorporated into cells whereupon the cap is cleaved and a pre-activated nucleoside released. 3'-deoxyadenosine (3'-dA) is a naturally-occurring adenosine analogue with established anti-cancer activity in vitro but limited bioavailability due to its rapid in vivo deamination by the circulating enzyme adenosine deaminase, poor uptake into cells and reliance on adenosine kinase for its activation. In order to overcome these limitations, 3'-dA was chemically modified to create the novel ProTide NUC-7738. Experimental Design: We describe the synthesis of NUC-7738. We determine the IC50 of NUC-7738 using pharmacokinetics (PK) and conduct genome-wide analyses to identify its mechanism of action using different cancer model systems. We validate these findings in cancer patients. Results: We show that NUC-7738 overcomes the cancer resistance mechanisms that limit the activity of 3'-dA and that its activation is dependent on ProTide cleavage by the enzyme histidine triad nucleotide binding protein 1. PK and tumour samples obtained from the ongoing first-in-human Phase 1 clinical trial of NUC-7738 further validate our in vitro findings and show NUC-7738 is an effective pro-apoptotic agent in cancer cells with effects on the NF-kappaB pathway. Conclusions: Our study provides proof that NUC-7738 overcomes cellular resistance mechanisms and support its further clinical evaluation as a novel cancer treatment within the growing pantheon of anti-cancer ProTides. Publisher PDF
Published: 2021
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30. Airway management during in-hospital cardiac arrest in adults: UK national survey and interview study with anaesthetic and intensive care trainees

Author: Goodwin, Laura, Samuel, Katie, Schofield, Behnaz, Voss, Sarah, Brett, Stephen J., Couper, Keith, Gould, Doug, Harrison, David, Lall, Ranjit, Nolan, Jerry P., Perkins, Gavin D., Soar, Jasmeet, Thomas, Matthew, Benger, Jonathan, and Research and Audit Federation of Trainees (RAFT) network
Subjects: Critical Care, Centre for Health and Clinical Research, respiratory system, Critical Care and Intensive Care Medicine
Abstract: Background: The optimal airway management strategy for in-hospital cardiac arrest is unknown. Methods: An online survey and telephone interviews with anaesthetic and intensive care trainee doctors identified by the United Kingdom Research and Audit Federation of Trainees. Questions explored in-hospital cardiac arrest frequency, grade and specialty of those attending, proportion of patients receiving advanced airway management, airway strategies immediately available, and views on a randomised trial of airway management strategies during in-hospital cardiac arrest. Results: Completed surveys were received from 128 hospital sites (76% response rate). Adult in-hospital cardiac arrests were attended by anaesthesia staff at 40 sites (31%), intensive care staff at 37 sites (29%) and a combination of specialties at 51 sites (40%). The majority (123/128, 96%) of respondents reported immediate access to both tracheal intubation and supraglottic airways. A bag-mask technique was used ‘very frequently’ or ‘frequently’ during in-hospital cardiac arrest by 111/128 (87%) of respondents, followed by supraglottic airways (101/128, 79%) and tracheal intubation (69/128, 54%). The majority (60/100, 60%) of respondents estimated that ≤30% of in-hospital cardiac arrest patients undergo tracheal intubation, while 34 (34%) estimated this to be between 31% and 70%. Most respondents (102/128, 80%) would be ‘likely’ or ‘very likely’ to recruit future patients to a trial of alternative airway management strategies during in-hospital cardiac arrest. Interview data identified several barriers and facilitators to conducting research on airway management in in-hospital cardiac arrest. Conclusions: There is variation in airway management strategies for adult in-hospital cardiac arrest across the UK. Most respondents would be willing to take part in a randomised trial of airway management during in-hospital cardiac arrest.
Published: 2021

31. Hoechst Is All You Need: Lymphocyte Classification with Deep Learning

Author: Cooper, Jessica, Um, In Hwa, Arandjelovi��, Ognjen, and Harrison, David J
Subjects: FOS: Computer and information sciences, Computer Science - Machine Learning, Artificial Intelligence (cs.AI), Computer Science - Artificial Intelligence, Computer Vision and Pattern Recognition (cs.CV), Computer Science - Computer Vision and Pattern Recognition, Machine Learning (cs.LG)
Abstract: Multiplex immunofluorescence and immunohistochemistry benefit patients by allowing cancer pathologists to identify several proteins expressed on the surface of cells, enabling cell classification, better understanding of the tumour micro-environment, more accurate diagnoses, prognoses, and tailored immunotherapy based on the immune status of individual patients. However, they are expensive and time consuming processes which require complex staining and imaging techniques by expert technicians. Hoechst staining is much cheaper and easier to perform, but is not typically used in this case as it binds to DNA rather than to the proteins targeted by immunofluorescent techniques, and it was not previously thought possible to differentiate cells expressing these proteins based only on DNA morphology. In this work we show otherwise, training a deep convolutional neural network to identify cells expressing three proteins (T lymphocyte markers CD3 and CD8, and the B lymphocyte marker CD20) with greater than 90% precision and recall, from Hoechst 33342 stained tissue only. Our model learns previously unknown morphological features associated with expression of these proteins which can be used to accurately differentiate lymphocyte subtypes for use in key prognostic metrics such as assessment of immune cell infiltration,and thereby predict and improve patient outcomes without the need for costly multiplex immunofluorescence., 15 pages, 4 figures
Published: 2021

32. Clinical and genetic characteristics of late-onset Huntington's disease

Author: Oosterloo, Mayke, Bijlsma, Emilia K., van Kuijk, Sander MJ., Minkels, Floor, de Die-Smulders, Christine EM., Bachoud-Lévi, Anne-Catherine, Bentivoglio, Anna-Rita, Biunno, Ida, Bonelli, Raphael M., Bronzova, Juliana, Burgunder, Jean-Marc, Dunnett, Stephen B., Ferreira, Joaquim J., Frich, Jan, Giuliano, Joe, Handley, Olivia J., Heiberg, Arvid, Illarioshkin, Sergey, Illmann, Torsten, Klempir, Jiri, Landwehrmeyer, G. Bernhard, Levey, Jamie, Mclean, Tim, Nielsen, Jørgen E., Koivisto, Susana Pro, Päivärinta, Markku, Pålhagen, Sven, Quarrell, Oliver, Ramos-Arroyo, Maria, Roos, Raymund A. C., Saft, Carsten, Sebastián, Ana Rojo, Tabrizi, Sarah J., Vandenberghe, Wim, Verellen-Dumoulin, Christine, Uhrova, Tereza, Wahlström+, Jan, Zaremba, Jacek (formerly Rödig, Verena, Baake, Barth, Katrin, Garde, Monica Bascuñana, Becanovic, Kristina, Bernard, Tomáš, Betz, Sabrina, Bos, Reineke, Come, Adrien, Guedes, Leonor Correia, Callaghan, Jenny, Capodarca, Selene, Charpentier, Sébastien, Vieira da Silva, Wildson, Di Renzo, Martina, Ecker, Daniel, Finisterra, Ana Maria, Fullam, Ruth, Genoves, Camille, Gilling, Mette, Horta, Andrea, Hvalstedt, Carina, Held, Christine, Hussain, Hasina, Koppers, Kerstin, Lamanna, Claudia, Laurà, Matilde, Descals, Asunción Martínez, Martinez-Horta, Saul, Mestre, Tiago, Minster, Sara, Monza, Daniela, Münkel, Kristina, Mütze, Lisanne, Oehmen, Martin, Padieu, Helene, Paterski, Laurent, Peppa, Nadia, Rindal, Beate, Rogers, Dawn, Røren (formerly Heinonen), Niini, Salgueiro, Ana, Šašinková, Pavla, Seliverstov, Yury, Taylor, Catherine, Timewell, Erika, Townhill, Jenny, Cubillo, Patricia Trigo, van Walsem, Marleen R., Witjes-Ané, Marie-Noelle, Witkowski, Grzegorz, Wright, Abigail, Yudina, Elizaveta, Zielonka, Daniel, Zielonka, Eugeniusz, Zinzi, Paola, Hecht, Karen, Herranhof, Brigitte, Holl (formerly Hödl), Anna, Kapfhammer, Hans-Peter, Koppitz, Michael, Lilek, Sabine, Magnet, Markus, Müller, Nicole, Otti, Daniela, Painold, Annamaria, Reisinger, Karin, Scheibl, Monika, Schöggl, Helmut, Ullah, Jasmin, Braunwarth, Eva-Maria, Brugger, Florian, Buratti, Lisa, Hametner, Eva-Maria, Hepperger, Caroline, Holas, Christiane, Hotter, Anna, Hussl, Anna, Larcher, Barbara, Mahlknecht, Philipp, Müller, Christoph, Pinter, Bernadette, Poewe, Werner, Reiter, Eva-Magdalena, Seppi, Klaus, Sprenger, Fabienne, Wenning, Gregor, Ladurner, Gunther, Lilek, Stefan, Sinadinosa, Daniela, Staffen, Wolfgang, Walleczek, Anna Maria, Linder, Christoph, Pirker, Walter, Liessens, Dirk, Calmeyn, Godelinde, Somers, Nele, Delvaux, Isabelle, Boogaerts, Andrea, Flamez, Anja, de Raedt, Sylvie, Alaerts, Nick, Slama, Hichem, Supiot, Frédéric, Constant, Eric, Gillardin, Anne-Françoise, Léonard, Marie-Claude, van de Wyngaerde, Françoise, Dupuis, Michel, Minet, Cécile, Ribaï, Pascale, Van Paemel, Dominique, van Reijen, Dimphna, Weckx, Petra, Kaiserova, Michaela, Šenkárová, Zuzana, Bezdíček, Ondřej, Klempíř, Jiří, Klempířová, Olga, Majerová-Ibarburu, Veronika, Nikolai, Tomáš, Roth, Jan, Stárková, Irena, Madsen, Louise Hasselstrøm, Møller, Anette Torvin, Hjermind, Lena, Jacobsen, Oda, Larsen, Ida Unmack, Lindquist, Suzanne, Nielsen, Jørgen, Regeur, Lisbeth, Roos, Peter, Stockholm, Jette, Vangsted-Hansen, Christina, Vinther-Jensen, Tua, Lolk, Annette, Lundsgaard, Marianne, Wermuth, Lene, Andersson, Christian, Nyberg, Clara, Sundblom, Jimmy, Peippo, Maarit, Sipponen, Marjatta, Bruun, Anu, Hartikainen, Paivi, Mäkipää, Seija, Ollokainen, Mari, Åman, Jaana, Kärppä, Mikko, Ignatius, Jaakko, Jääskeläinen, Outi, Kajula, Outi, Moilanen, Jukka, Mustonen, Aki, Santala, Maire, Eklund, Pia, Hiivola, Heli, Hyppönen, Hannele, Martikainen, Kirsti, Ojala, Marjut, Tähkäpää, Sirkku, Tuuha, Katri, Allain, Philippe, Bonneau, Dominique, Bost, Marie, Gohier, Bénédicte, Guérid, Marie-Anne, Olivier, Audrey, Prouzet, Julie, Prundean, Adriana, Scherer-Gagou, Clarisse, Verny, Christophe, Babiloni, Blandine, Bled, Déborah, Debruxelles, Sabrina, Duché, Charlotte, Fraisse, Sonia, Goizet, Cyril, Jameau, Laetitia, Lafoucrière, Danielle, Spampinato, Umberto, Couttier, Julien, Debilly, Bérengère, Delaigue, Christine, Derost, Philippe, Durif, Franck, Germain, Véronique, Legendre, Perrine, Loiseau, Sylvie, Marques, Ana, Ulla, Miguel, Vidal, Tiphaine, Badei, Farideh, Boissé, Marie-Françoise, Boudali, Lotfi, Cleret de Langavant, Laurent, Lemoine, Laurie, Morgado, Graca, Youssov, Katia, Annic, Agnès, Barthélémy, Recka, De Bruycker, Christelle, Cabaret, Maryline, Carette, Anne-Sophie, Carrière, Nicolas, Decorte, Eric, Defebvre, Luc, Delliaux, Marie, Delval, Arnaud, Depelchin, Alizé, Destee, Alain, Dewulf-Pasz, Nelly, Dondaine, Thibaut, Dugauquier, Florence, Dujardin, Kathy, Hopes, Lucie, Krystkowiak, Pierre, Lemaire, Marie-Hélène, Manouvrier, Sylvie, Mutez, Eugénie, Peter, Mireille, Plomhause, Lucie, Sablonnière, Bernard, Simonin, Clémence, Tard, Céline, Thibault-Tanchou, Stéphanie, Vuillaume, Isabelle, Bellonet, Marcellin, Blin, Stéphanie, Chen, Simone, Masmoudi, Kamel, Morin, Gilles, Roussel, Martine, Tir, Mélissa, Schüler, Béatrice, Wannepain, Sandrine, Zouitina, Yassine, Azulay, Jean-Philippe, Delfini, Marie, Eusebio, Alexandre, Fluchere, Frédérique, Guenam, Aicha, Mundler, Laura, Nguyen, Karine, Benaich, Sandra, Brice, Alexis, Boster, Sarah, Charles, Perrine, Durr, Alexandra, Ewenczyk, Claire, Francisque, Hélène, Jauffret, Céline, Justo, Damian, Kassar, Abdulrahman, Klebe, Stephan, Lesne, Fabien, Milani, Paolo, Monin, Marie-Lorraine, Monnier, Tiffany, Roze, Emmanuel, Tataru, Alina, Tchikviladzé, Maya, Bioux, Sandrine, Bliaux, Evangeline, Girard, Carole, Guyant-Maréchal, Lucie, Hannequin, Didier, Hannier, Véronique, Jourdain, Séverine, Maltête, David, Pouliquen, Dorothée, Anheim, Mathieu, Barun, Nadia, Lagha-Boukbiza, Ouhaid, Longato, Nadine, Marcel, Christophe, Phillipps, Clélie, Rudolf, Gabrielle, Steinmetz, Gisèle, Tranchant, Christine, Wagner, Caroline, Zimmermann, Marie-Agathe, Blondeau, Leily, Calvas, Fabienne, Cheriet, Samia, Delabaere, Helène, Demonet, Jean-François, Marquine, Laurent, Pariente, Jérémie, Pierre, Michèle, Pomies, Elsa, Rolland, Sandrine, Souyris, Corinne, Kosinski, Christoph Michael, Milkereit, Eva, Probst, Daniela, Reetz, Kathrin, Sass, Christian, Schiefer, Johannes, Schlangen, Christiane, Werner, Cornelius J., Beuth, Markus, Gelderblom, Harald, Priller, Josef, Prüß, Harald, Spruth, Eike, Thiel, Silvia, Andrich, Jürgen, Ellrichmann, Gisa, Herrmann, Lennard, Hoffmann, Rainer, Kaminski, Barbara, Kraus, Peter, Stamm, Christiane, Ganos, Christos, Stubbe, Lars, Tadic, Vera, Tübing, Jennifer, Lange, Herwig, Bosredon, Cecile, Hunger, Ulrike, Löhle, Matthias, Maass, Antonia, Ossig, Christiana, Schmidt, Simone, Storch, Alexander, Wolz, Annett, Wolz, Martin, Kohl, Zacharias, Kozay, Christina, Winkler, Jürgen, Bergmann, Ulrike, Böringer, Regina, Capetian, Philipp, Kammel, Gerit, Lambeck, Johann, Mächtel, Miriam, Meier, Simone, Rijntjes, Michel, Zucker, Birgit, Boelmans, Kai, Goerendt, Ines, Heinicke, Walburgis, Hidding, Ute, Lewerenz, Jan, Münchau, Alexander, Orth, Michael, Schmalfeld, Jenny, Zittel, Simone, Diercks, Gabriele, Dressler, Dirk, Francis, Flverly, Gayde-Stephan, Sabine, Gorzolla, Heike, Kramer, Bianca, Minschke, Rebecca, Schrader, Christoph, Tacik, Pawel, Ribbat+, Michael, Longinus, Bernhard, Möller, Carsten, Bürk, Katrin, Lüsebrink, Antje, Mühlau, Mark, Peinemann, Alexander, Städtler, Michael, Weindl, Adolf, Winkelmann, Juliane, Ziegler, Cornelia, Bechtel, Natalie, Beckmann, Heike, Bohlen, Stefan, Göpfert, Nicole, Hölzner, Eva, Reilmann, Ralf, Rohm, Stefanie, Rumpf, Silke, Schepers, Sigrun, Weber, Nathalia, Bachmeier, Michael, Dose, Matthias, Hofstetter, Nina, Marquard, Ralf, Mühlbäck, Alzbeta, Buck, Andrea, Connemann, Julia, Geitner, Carolin, Kesse, Andrea, Landwehrmeyer, Bernhard, Lezius, Franziska, Nepper, Solveig, Niess, Anke, Schneider, Ariane, Schwenk, Daniela, Süssmuth, Sigurd, Trautmann, Sonja, Vogel, Melanie, Weydt, Patrick, Musacchio, Thomas, Leypold, Christine, Nöth, Kerstin, Cormio, Claudia, Difruscolo, Olimpia, Franco, Giovanni, Nuzzi, Angela, Sciruicchio, Vittorio, Serpino, Claudia, de Tommaso, Marina, Calandra-Buonaura, Giovanna, Capellari, Sabina, Cortelli, Pietro, Gallassi, Roberto, Poda, Roberto, Scaglione, Cesa, Agosti, Chiara, Barlati, Sergio, Compostella, Silvia, Marchina, Eleonora, Padovani, Alessando, Figorilli, Michela, Marrosu, Francesco, Muroni, Antonella, Piras, Valeria, Vacca, Melisa, Bertini, Elisabetta, Bartoli, Caterina, Fortunato, Fernanda, Ghelli, Elena, Ginestroni, Andrea, Mechi, Claudia, Paganini, Marco, Piacentini, Silvia, Pradella, Silvia, Romoli, Anna Maria, Sorbi, Sandro, Abbruzzese, Giovanni, Bandettini di Poggio, Monica, Ferrandes, Giovanna, Mandich, Paola, Marchese, Roberta, Di Maria, Emilio, Tamburini, Tiziano, Albanese, Alberto, Castagliuolo, Simona, Castaldo, Anna, Di Donato, Stefano, Di Bella, Daniela, Gellera, Cinzia, Genitrini, Silvia, Mariotti, Caterina, Nanetti, Lorenzo, Panzeri, Marta, Paridi, Dominga, Soliveri, Paola, Spagnolo, Francesca, Taroni, Franco, Tomasello, Chiara, De Michele, Giuseppe, Di Maio, Luigi, Rinaldi, Carlo, Massarelli, Marco, Peluso, Silvio, Roca, Alessandro, Russo, Cinzia Valeria, Salvatore, Elena, Sorrentino, Pierpaolo, Tucci, Tecla, Cannella, Milena, Codella, Valentina, De Gregorio, Francesca, De Nicola, Annunziata, Elifani, Francesca, Esposito, Chiara, Martino, Tiziana, Mazzante, Irene, Petrollini, Martina, Simonelli, Maria, Vezza, Maurizio, Squitieri, Ferdinando, D'Alessio, Barbara, Lovo, Francesca, Bentivoglio, Anna Rita, Bove, Francesco, Catalli, Claudio, Di Giacopo, Raffaella, Fasano, Alfonso, Frontali, Marina, Guidubaldi, Arianna, Ialongo, Tamara, Jacopini, Gioia, Loria, Giovanna, Modoni, Anna, Petracca, Martina, Piano, Carla, Chiara, Piccininni, Quaranta, Davide, Romano, Silvia, Soleti, Francesco, Solito, Marcella, Spadaro, Maria, Torlizzi, Flavia, Coarelli, Giulia, Ferraldeschi, Michela, Ristori, Giovanni, van Hout, Monique S. E., van Vugt, Jeroen P. P., Marit de Weert, A., Verhoeven, Marloes, Dekker, Meike, Klooster, Jesper, Leenders, Nico, van Oostrom, Joost, Kremer, Berry, Baake, Verena, van den Bogaard, Simon J. A., Dumas, Eve M., t Hart, Ellen P., Hogenboom, Marye, Jacobs, Milou, Jurgens, Caroline, Kampstra, Anne, Schoonderbeek, Anne, Witjes-Ané, Marie-Noëlle, Duits, Annelien, Waber, Mirella, Verstappen, Carla, Blinkenberg, Ellen Økland, Hauge, Erik, Tyvoll, Hilde, Aaserud, Olaf, Aanonsen, Nils Olaf, Bjørgo, Kathrine, Borgerød, Nancy, Dramstad, Elisabeth, Fannemel, Madeleine, Frich, Jan C., Gørvell, Per F., Haggag, Kathrine, Johannessen, Cecilie Haggag, Retterstøl, Lars, Røsby, Oddveig, Rummel, Jutta, Sikiric, Alma, Stokke, Bodil, van Walsem, Marleen, Wehus, Ragnhild, Arntsen, Vibeke, Bjørnevoll, Inga, Sando, Sigrid Botne, Haug, Marte Gjøl, Størseth, Hanna Haugan, Østern, Rune, Paulsen, Julie, Dziadkiewicz, Artur, Konkel, Agnieszka, Narożańska, Ewa, Nowak, Malgorzata, Robowski, Piotr, Sitek, Emilia, Slawek, Jaroslaw, Soltan, Witold, Szinwelski, Michal, Arkuszewski, Michał, Błaszczyk, Magdalena, Boczarska-Jedynak, Magdalena, Ciach-Wysocka, Ewelina, Gorzkowska, Agnieszka, Jasińska-Myga, Barbara, Kaczmarczyk, Aleksandra, Kłodowska – Duda, Gabriela, Opala, Grzegorz, Rudzińska, Monika, Stompel, Daniel, Banaszkiewicz, Krzysztof, Boćwińska, Dorota, Bojakowska-Jaremek, Kamila, Dec, Małgorzata, Grabska, Natalia, Krawczyk, Malgorzata, Kubowicz, Ewelina, Malec-Litwinowicz, Michalina, Stenwak, Agata, Szczudlik, Andrzej, Szczygieł, Elżbieta, Wójcik, Magdalena, Wasielewska, Anna, Anna Bryl, Jacek Anioła, Ciesielska, Anna, Klimberg, Aneta, Marcinkowski, Jerzy, Samara, Husam, Sempołowicz, Justyna, Wiśniewski, Bartłomiej, Gogol (formerly Kalbarczyk), Anna, Janik, Piotr, Jamrozik, Zygmunt, Kaminska, Anna, Kwiecinski+, Hubert, Antczak, Jakub, Jachinska, Katarzyna, Krysa, Wioletta, Rakowicz, Maryla, Rola, Rafal, Ryglewicz, Danuta, Sienkiewicz-Jarosz, Halina, Stępniak, Iwona, Sułek, Anna, Zaremba, Jacek, Zdzienicka, Elzbieta, Ziora-Jakutowicz, Karolina, Januário, Cristina, Júlio, Filipa, Almeida, Manuel, Calado, Ana, Dias, Margarida, Morgado, Joana, Semedo, Cristina, Coelho, Miguel, Magalhães, Andreia, Mendes, Tiago, Neutel, Dulce, Rodrigues, Filipe, Valadas, Anabela, Costa, Cristina, Cardoso, Helena, Santos, Mariana, Cação, Gonçalo, Cavaco, Sara, Damásio, Joana, Fernandes, Joana, Gonçalves, Alexandra, Loureiro, Rui, Moreira, Inês, Magalhães, Marina, Salgado, Paula, Andrade, Carlos, Costa, Andreia, Garrett, Carolina, Gago, Miguel, Guimarães, Joana, Massano, João, Meireles, Joana, Monteiro, Ana, Khasanova, Diana, Zalyalova, Zuleykha, Klyushnikov, Sergey, Sidorova, Olga, Smirnov, Oleg, Antonova, Victoria, Kopishinskaya, Svetlana, Korotysh, Maria, Magzhanov, Rim, Saifullina, Elena, Kurbatov, Sergey, Solis, Pilar, Herrera, Carmen Durán, Moreno, Patrocinio Garcia, Bas, Jordi, Busquets, Núria, Calopa, Matilde, Classen, Serge Jaumà, Dedichá, Nadia Rodríguez, Buongiorno, María Teresa, María, Andrés de la Cerda Santa, Muñoz, Esteban, Santacruz, Pilar, Barbera, Miquel Aguilar, Pardo, Sonia Arribas, Guia, Dolors Badenes, Calzado, Noemi, Hernanz, Laura Casas, Tartari Díaz-Zorita, Juan Pablo, Catena, Judit López, Ferrer, Pilar Quiléz, Carruesco, Gemma Tome, Robert, Misericordia Floriach, Viladrich, Cèlia Mareca, Roca, Elvira, Ruiz Idiago, Jesús Miguel, Riballo, Antonio Villa, Campolongo, Antonia, Fernandez de Bobadilla, Ramon, Bojarsky, Jaime Kulisevsky, Pagonabarraga, Javier, Perez, Jesus Perez, Ribosa, Roser, Villa, Carolina, Acera Gil, Maria Angeles, Corrales, Koldo Berganzo, Gomez Esteban, Juan Carlos, González, Amaia, Merino, Beatriz Tijero, Cubo, Esther, Polo, Cecilia Gil, Mariscal, Natividad, Sánchez, Jesús, Romero, Sandra Gutierrez, Arbelo, José Matías, Malo de Molina, Rocío, Martín, Idaira, Periañez, Juan Manuel, Udaeta, Beatriz, Alonso-Frech, Fernando, Loarte, María del Valle, Barrero, Francisco, Morales, Blas, Frades, Belén, Villanueva, Marina Ávila, Zea Sevilla, Maria Ascension, Fenollar, María del Mar, García-Ramos García, Rocío, Villanueva, Clara, Bascuñana, Mónica, Ventura, Marta Fatás, Caldentey, Juan García, Ribas, Guillermo García, García de Yébenes, Justo, López-Sendón Moreno, José Luis, Barral, Verónica Mañanes, Feliz, Cici, García Ruíz, Pedro José, García, Ana, López, Rosa Guerrero, Bárcenas, Antonio Herranz, Martínez-Descals, Asunción, Pueyo, Angel Martínez, Martin, Veronica Puertas, Martínez, Noelia Rodríguez, Montojo, Teresa, Sainz Artiga, María José, Sánchez, Vicenta, Alarcón, María Dolores, Almagro, Carmen Antúnez, Diéguez, Esther, Fortuna, Lorenza, Legaz, Agustina, Manzanares, Salvadora, Muñoz, Juan Marín, Antequera Torres, María Martirio, Perea, Fuensanta Noguera, Vivancos, Laura, González, Sonia, Guisasola, Luis Menéndez, Prieto, Marta Para, Ribacoba, René, Salvador, Carlos, Lozano, Pablo Sánchez, Ramirez, Inés Legarda, Benito, Dolors Moragues, Arques, Penelope Navas, Lopera, Monica Rodriguez, Pastor, Barbara Vives, Gaston, Itziar, Garcia-Amigot, Fermin, Martinez-Jaurrieta, Maria Dolores, Ramos-Arroyo, Maria Antonia, Adarmes, Astrid, Bernal-Escudero, Maravilla, Carrillo, Fátima, Jesús, Silvia, Mir, Pablo, Vargas-González, Laura, Hermoso, Fátima Damas, García Moreno, José Manuel, Jaramillo, Javier Abril, Lucena, Carolina Mendez, Pacheco Cortegana, Eva María, Peña, José Chacón, Redondo, Luis, Sánchez, Violeta Sánchez, Fernandez, Cristina Melgar, Romero Lemos, María Dolores, Mata, Maite Paredes, Casado, Rocío Villagrán, Bosca, Maria, Burguera, Juan Andres, Brugada, Francisco Castera, Millán Salvador, Jose Maria, Vilaplana, Carmen Peiró, Solís, Pilar, Figuerola, Begoña Jeweinat, Palanca, Paloma Millan, Diago, Elena Bellosta, López del Val, Javier, Martinez, Laura Martinez, López, Elena, Høsterey-Ugander, Ulrika, Fredlund, Gunnel, Constantinescu, Radu, Lewin, Kajsa, Neleborn-Lingefjärd, Liselotte, Berglund, Maria, Berglund, Peter, Linnsand, Petra, Petersén, Åsa, Reimer, Jan, Widner, Håkan, Esmaeilzadeh, Mouna, Tedroff, Joakim, Winnberg, Elisabeth, Benaminov, Stanislav, Björnsson, Elisabeth, Merrick, Daniel, Paucar, Martin, Svenningsson, Per, Wallden, Tina, Berglund, Måns, Loutfi, Ghada, Olofsson, Carina, Stattin, Eva-Lena, Westman, Laila, Wikström, Birgitta, Ekwall, Camilla, Göller, Marie-Lousie, Johansson, Anders, Niemelä, Valter, Nyholm, Dag, Wiklund, Leif, Koehli, Jessica, Stebler, Yanik, Kaelin, Alain, Romero, Irene, Schüpbach, Michael, Zaugg, Sabine Weber, Esposito, Federica, Good, Jean-Marc, Paus, Karin, Vingerhoets, Francois, Wider+, Christian, Jung, Hans H., Petersen, Jens A., Ligon-Auer, Maria, Mihaylova, Violeta, Downie, Lorna, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, Simpson, Sheila A., Summers, Fiona, Ure, Alexandra, Vaughan, Vivien, Harrower, Timothy, Vernon, Nathan, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, de Souza (Keylock), Jenny, Piedad, John, Rickards, Hugh, Wright, Jan, Haig-Brown, Diane, Craven, Janet, Pallett, Andrew, Simpson, Steve, Weekes, Rebecca, Coulthard, Elizabeth, Gethin, Louise, Hayward, Beverley, Sieradzan, Kasia, Barker, Roger A., O'Keefe, Deidre, Gerrtiz (nee Di Pietro), Anna, Fisher, Kate, Goodman, Anna, Hill, Susan, Mason, Sarah, Swain, Rachel, Guzman, Natalie Valle, Busse, Monica, Butcher, Cynthia, Dunnett, Stephen, Clenaghan, Catherine, Hunt, Sarah, Jones, Lesley, Jones, Una, Khalil, Hanan, Owen, Michael, Price, Kathleen, Rosser, Anne, Goudie, David, Buchanan, Lindsay, Mcfadyen, Paula, Tonner, Alison, Taylor, Anne-Marie, Edwards, Maureen, Carrie, Ho, Mcgill, Marie, Porteous, Mary, Pearson, Pauline, Irvine, Sarah, Brockie, Peter, Foster, Jillian, Johns, Nicola, Mckenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Neumann, Christian, Patterson, Kirsten, Thomson, David, Deith, Catherine, Ireland, Jane, Ritchie, Stuart, Brown, Pauline, Burrows, Liz, Fletcher, Amy, Harding, Alison, Harrison, Kaye, Laver, Fiona, Silva, Mark, Thomson, Aileen, Chu, Carol, Evans, Carole, Gallentree, Deena, Hamer, Stephanie, Kraus, Alison, Markova, Ivana, Raman, Ashok, Rowett, Liz, Andrew, Alyson, Frost, Julie, Noad, Rupert, Cosgrove, Jeremy, Gallantree, Deena, Hobson, Emma, Jamieson, Stuart, Longthorpe, Mandy, Musgrave, Hannah, Peacy, Caroline, Toscano, Jean, Wild, Sue, Yardumian, Pam, Clayton, Carole, Dipple, Heather, Freire-Patino, Dawn, Hallam, Caroline, Middleton, Julia, Alusi, Sundus, Davies, Rhys, Foy, Kevin, Gerrans, Emily, Pate, Louise, Anjum, Uruj, Coebergh, Jan, Eddy, Charlotte, Lahiri, Nayana, Mcentagart, Meriel, Patton, Michael, Peterson, Maria, Rose, Sarah, Andrews, Thomasin, Dougherty, Andrew, Golding, Charlotte, Kavalier, Fred, Laing, Hana, Lashwood, Alison, Robertson, Dene, Ruddy, Deborah, Santhouse, Alastair, Whaite, Anna, Gosling (nee Brown), Stefanie, Bruno, Stefania, Chu, Elvina, Doherty, Karen, Haider, Salman, Hensman, Davina, Lewis, Monica, Novak, Marianne, Patel, Aakta, Robertson, Nicola, Rosser, Elisabeth, Tabrizi, Sarah, Taylor, Rachel, Warner, Thomas, Wild, Edward, Ackermann, Oda, Duport, Sophie, Scott, Adrienne, Stoy, Nicholas, Vaughn, Jenny, Arran, Natalie, Bek, Judith, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Krishnamoorthy, Ashok, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iris, Verstraelen (formerly Ritchie), Nichola, Westmoreland, Leann, Cass, Ginette, Davidson, Lynn, Davison, Jill, Fullerton, Neil, Holmes, Katrina, Komati, Suresh, Mcdonnell, Sharon, Mohammed, Zeid, Morgan, Karen, Savage, Lois, Singh, Baldev, Wood, Josh, Knight, Caroline, O'Neill, Mari, Purkayastha, Debasish Das, Nemeth, Andrea H., Siuda, Gill, Valentine, Ruth, Dixon, Kathryn, Armstrong, Richard, Harrison, David, Hughes, Max, Large, Sandra, Donovan, John O., Palmer, Amy, Parkinson, Andrew, Soltysiak, Beverley, Timings, Leanne, Williams, Josh, Burn, John, Bailey, Wendy, Coleman, Caroline, Majeed, Tahir, Verstraelen (Ritchie), Nicola, Barrett, Wendy, Aileen, Ho, Bandmann, Oliver, Bradbury, Alyson, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Gill, Paul, Kazoka, Mbombe, O'Donovan, Kirsty, Nevitt, Louise, Taylor, Cat, Tidswell, Katherine, Kipps, Christopher, Mackinnon, Lesley, Agarwal, Veena, Hayward, Elaine, Gunner, Kerry, Harris, Kayla, Anderson, Mary, Heywood, Melanie, Keys, Liane, Smalley, Sarah, El-Nimr, George, Duffell, Allison, Wood, Sue, Kennedy (nee Smith), Karen, Gowers, Lesley, Powell, Kingsley, Bethwaite, Pamela, Edwards, Rachel, Fuller, Kathleen, Phillips, Michelle, Tan, Louis, Lau, Puay Ngoh, Pica, Emmanuel, Roos, Raymund AC., Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), MUMC+: KIO Kemta (9), Epidemiologie, RS: CAPHRI - R2 - Creating Value-Based Health Care, Klinische Genetica, MUMC+: DA KG Polikliniek (9), and RS: GROW - R4 - Reproductive and Perinatal Medicine
Subjects: Male, HD, 0301 basic medicine, Pediatrics, Neurology, Huntingtin Protein/genetics, FEATURES, Disease, Neuropsychological Tests, 0302 clinical medicine, Cognitive Dysfunction/psychology, Medicine, Family history, Postural Balance, Huntington Disease/genetics, Huntingtin Protein, education.field_of_study, Chorea/physiopathology, Huntington's disease, Sensation Disorders/physiopathology, Middle Aged, Dystonia, Settore MED/26 - NEUROLOGIA, Huntington Disease, neurodegenerative disorders, Sensation Disorders, Disease Progression, Female, medicine.symptom, Adult, medicine.medical_specialty, Population, Age of onset, Late-onset Huntington's disease, Geriatrics and Gerontology, Neurology (clinical), 03 medical and health sciences, AGE, Chorea, Humans, Cognitive Dysfunction, education, Dystonia/physiopathology, Gait Disorders, Neurologic/physiopathology, Gait Disorders, Neurologic, business.industry, medicine.disease, Gait, 030104 developmental biology, Trinucleotide Repeat Expansion, business, 030217 neurology & neurosurgery, Balance problems
Abstract: Background: The frequency of late-onset Huntington's disease (>59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P
Published: 2019
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33. Verba volant. Aphasie et mutisme dans les Mémoires de Saint-Simon

Author: Harrison, David
Subjects: Applied Mathematics, General Mathematics
Abstract: Harrison David. Verba volant. Aphasie et mutisme dans les Mémoires de Saint-Simon. In: Cahiers Saint Simon, n°47, 2019. Saint-Simon et les égarements du Langage. Journée d’études du samedi 16 mars 2019. pp. 41-50.
Published: 2019
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34. Realising the full potential of data-enabled trials in the UK: a call for action

Author: Sydes, Matthew R, Barbachano, Yolanda, Bowman, Louise, Denwood, Tom, Farmer, Andrew, Garfield-Birkbeck, Steph, Gibson, Martin, Gulliford, Martin C, Harrison, David A, Hewitt, Catherine, Logue, Jennifer, Navaie, Will, Norrie, John, Quint, Jennifer K, Rycroft-Malone, Jo, Sheffield, Jonathan, Smeeth, Liam, Sullivan, Frank, Tizzard, Juliet, Walker, Paula, Wilding, John, Williamson, Paula R, Landray, Martin, Morris, Andrew, Walker, Rhoswyn R, Williams, Hywel C, and Valentine, Janet
Subjects: General Medicine
Abstract: Rationale: Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile, and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHR). Opportunities exist to utilise these in innovative ways to decrease duplication of effort, and speed trial recruitment, conduct and follow-up.Approach: The National Institute of Health Research (NIHR), Health Data Research UK (HDR UK) and Clinical Practice Research Datalink (CPRD) co-organised a national workshop to accelerate the agenda for “data-enabled clinical trials”. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation.Reflection: Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a “route map” to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution.Discussion: EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial’s specific challenges. The short-term emphasis should be on facilitating patient recruitment and for post-marketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR’s funding call. ambitious data-enabled trials at scale. There is the opportunity for the United Kingdom to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.
Published: 2021

35. Genetic mechanisms of critical illness in Covid-19

Author: Pairo-Castineira, Erola, Clohisey, Sara, Klaric, Lucija, Bretherick, Andrew D., Rawlik, Konrad, Pasko, Dorota, Walker, Susan, Parkinson, Nick, Head Fourman, Max, Russell, Clark D., Furniss, James, Richmond, Anne, Gountouna, Elvina, Wrobel, Nicola, Harrison, David, Wang, Bo, Wu, Yang, Meynert, Alison, Griffiths, Fiona, Oosthuyzen, Wilna, Kousathanas, Athanasios, Moutsianas, Loukas, Yang, Zhijian, Zhai, Ranran, Zheng, Chenqing, Grimes, Graeme, Beale, Rupert, Millar, Jonathan, Shih, Barbara, Keating, Sean, Zechner, Marie, Haley, Chris, Porteous, David J., Hayward, Caroline, Yang, Jian, Knight, Julian, Summers, Charlotte, Shankar-Hari, Manu, Klenerman, Paul, Turtle, Lance, Ho, Antonia, Moore, Shona C., Hinds, Charles, Horby, Peter, Maslove, David, Ling, Lowell, McAuley, Danny, Montgomery, Hugh, Walsh, Timothy, Pereira, Alex, Renieri, Alessandra, The GenOMICC Investigators, ., The ISARIC-4C Investigators, ., The Covid-19 Human Genetics Initiative, ., 23andMe Investigators, ., BRACOVID Investigators, ., Gen-COVID Investigators, ., Shen, Xia, Ponting, Chris P., Fawkes, Angie, Tenesa, Albert, Caulfield, Mark, Scott, Richard, Rowan, Kathy, Openshaw, Peter J.M., Semple, Malcolm G., Law, Andrew, Vitart, Veronique, Wilson, James F., and Baillie, J. Kenneth
Abstract: Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by Covid-19. Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study(GWAS) in 2244 critically ill Covid-19 patients from 208 UK intensive care units (ICUs). We identify and replicate novel genome-wide significant associations, on chr12q24.13 (rs10735079, p=1.65 × 10-8) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), on chr19p13.2 (rs2109069, p=2.3 × 10-12) near the gene encoding tyrosine kinase 2 (TYK2), on chr19p13.3 (rs2109069, p=3.98 × 10-12) within the gene encoding dipeptidyl peptidase 9 (DPP9), and on chr21q22.1 (rs2236757, p=4.99 × 10-8) in the interferon receptor gene IFNAR2. We identify potential targets for repurposing of licensed medications: using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease; transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms, and mediators of inflammatory organ damage in Covid-19. Both mechanisms may be amenable to targeted treatment with existing drugs. Large-scale randomised clinical trials will be essential before any change to clinical practice.
Published: 2021

36. Reduced exposure to vasopressors through permissive hypotension to reduce mortality in critically ill people aged 65 and over: the 65 RCT

Author: Mouncey, Paul R, Richards-Belle, Alvin, Thomas, Karen, Harrison, David A, Sadique, M Zia, Grieve, Richard D, Camsooksai, Julie, Darnell, Robert, Gordon, Anthony C, Henry, Doreen, Hudson, Nicholas, Mason, Alexina J, Saull, Michelle, Whitman, Chris, Young, J Duncan, Lamontagne, François, Rowan, Kathryn M, and 65 trial investigators
Abstract: BACKGROUND: Vasopressors are administered to critical care patients to avoid hypotension, which is associated with myocardial injury, kidney injury and death. However, they work by causing vasoconstriction, which may reduce blood flow and cause other adverse effects. A mean arterial pressure target typically guides administration. An individual patient data meta-analysis (Lamontagne F, Day AG, Meade MO, Cook DJ, Guyatt GH, Hylands M, et al. Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock. Intensive Care Med 2018;44:12-21) suggested that greater exposure, through higher mean arterial pressure targets, may increase risk of death in older patients. OBJECTIVE: To estimate the clinical effectiveness and cost-effectiveness of reduced vasopressor exposure through permissive hypotension (i.e. a lower mean arterial pressure target of 60-65 mmHg) in older critically ill patients. DESIGN: A pragmatic, randomised clinical trial with integrated economic evaluation. SETTING: Sixty-five NHS adult general critical care units. PARTICIPANTS: Critically ill patients aged ≥ 65 years receiving vasopressors for vasodilatory hypotension. INTERVENTIONS: Intervention - permissive hypotension (i.e. a mean arterial pressure target of 60-65 mmHg). Control (usual care) - a mean arterial pressure target at the treating clinician's discretion. MAIN OUTCOME MEASURES: The primary clinical outcome was 90-day all-cause mortality. The primary cost-effectiveness outcome was 90-day incremental net monetary benefit. Secondary outcomes included receipt and duration of advanced respiratory and renal support, mortality at critical care and acute hospital discharge, and questionnaire assessment of cognitive decline and health-related quality of life at 90 days and 1 year. RESULTS: Of 2600 patients randomised, 2463 (permissive hypotension, n = 1221; usual care, n = 1242) were analysed for the primary clinical outcome. Permissive hypotension resulted in lower exposure to vasopressors than usual care [mean duration 46.0 vs. 55.9 hours, difference -9.9 hours (95% confidence interval -14.3 to -5.5 hours); total noradrenaline-equivalent dose 31.5 mg vs. 44.3 mg, difference -12.8 mg (95% CI -18.0 mg to -17.6 mg)]. By 90 days, 500 (41.0%) patients in the permissive hypotension group and 544 (43.8%) patients in the usual-care group had died (absolute risk difference -2.85%, 95% confidence interval -6.75% to 1.05%; p = 0.154). Adjustment for prespecified baseline variables resulted in an odds ratio for 90-day mortality of 0.82 (95% confidence interval 0.68 to 0.98) favouring permissive hypotension. There were no significant differences in prespecified secondary outcomes or subgroups; however, patients with chronic hypertension showed a mortality difference favourable to permissive hypotension. At 90 days, permissive hypotension showed similar costs to usual care. However, with higher incremental life-years and quality-adjusted life-years in the permissive hypotension group, the incremental net monetary benefit was positive, but with high statistical uncertainty (£378, 95% confidence interval -£1347 to £2103). LIMITATIONS: The intervention was unblinded, with risk of bias minimised through central allocation concealment and a primary outcome not subject to observer bias. The control group event rate was higher than anticipated. CONCLUSIONS: In critically ill patients aged ≥ 65 years receiving vasopressors for vasodilatory hypotension, permissive hypotension did not significantly reduce 90-day mortality compared with usual care. The absolute treatment effect on 90-day mortality, based on 95% confidence intervals, was between a 6.8-percentage reduction and a 1.1-percentage increase in mortality. FUTURE WORK: Future work should (1) update the individual patient data meta-analysis, (2) explore approaches for evaluating heterogeneity of treatment effect and (3) explore 65 trial conduct, including use of deferred consent, to inform future trials. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10580502. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 14. See the NIHR Journals Library website for further project information.
Published: 2021

37. sj-pdf-1-inc-10.1177_17511437211047180 �� Supplemental Material for Timing and burden of persistent critical illnessin UK intensive care units: An observational cohort study

Author: Harrison, David A, Creagh-Brown, Ben C, and Rowan, Kathryn M
Subjects: 111708 Health and Community Services, FOS: Clinical medicine, Cardiology, 110323 Surgery, FOS: Health sciences, 110305 Emergency Medicine
Abstract: Supplemental Material, sj-pdf-1-inc-10.1177_17511437211047180 for Timing and burden of persistent critical illnessin UK intensive care units: An observational cohort study by David A Harrison, Ben C Creagh-Brown and Kathryn M Rowan in Journal of the Intensive Care Society
Published: 2021
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38. Irish National ICU Audit Annual Report 2018

Author: Dwyer, Rory, Baggot, Mary, Brych, Olga, Cronin, Marina, Fleming, Andrew, Gaffney, Alan, Harrison, David, Kelly, Fionnola, Marsh, Brian, Mc Donnell, Tim, Moriarty, Jeanne, Motherway, Catherine, Pecak, Magdalena, Power, Michael, Treanor, Fionnuala, Whelan, Eileen, Committee, The ICU Audit Governance, and (NOCA), The National Office of Clinical Audit
Subjects: paediatric, 110310 Intensive Care, Intensive care, adult, FOS: Clinical medicine, HSE hospitals, The Paediatric Intensive Care Audit Network (PICANet), The Intensive Care National Audit and Research Centre (ICNARC), audit, adult health service, intensive care unit, Ireland
Abstract: This report is based on data from 18 Units in 15 hospitals which undertook 70% of all critical care activity in Health Service Executive (HSE)-funded hospitals during 2018. Units varied widely in numbers of beds, numbers of admissions, and in case mix on admission to the Unit. Some Units were High Dependency Units (HDUs), some were Intensive Care Units (ICUs), some were mixed ICU/HDU, and some were specialist Units (e.g. neurosurgical, cardiothoracic). Our data provide a detailed insight into the characteristics of each Unit and allow Units to benchmark themselves against comparable Units. In addition, the data allow comparisons between Units in Ireland and those in the United Kingdom (UK).
Published: 2021
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39. Influence of the initial surface roughness on the ablation efficiency of metals

Author: Ruck, Simon, Harrison, David K., deSilva, Anjali, Dikel, Simon, Kleefoot, Max-Jonathan, and Riegel, Harald
Abstract: Die Laserablation als Verfahren der Pr��zisionsbearbeitung gewinnt sowohl in den Bereichen der Forschung als auch der industriellen Fertigung an Bedeutung. Insbesondere f��r industrielle Anwendungen stellt neben den erreichbaren Genauigkeiten die Prozesseffizient einen wichtigen Faktor dar. Meist werden f��r Untersuchungen in der Forschung polierte Oberfl��chen f��r die Untersuchung des Ablationsprozesses verwendet. Ziel dieser Arbeit ist die Untersuchung der Ablationseffizienz von Metallen bei der Bearbeitung mit gepulster Laserstrahlung in Abh��ngigkeit der Oberfl��chenrauheit. Erste Ergebnisse zeigen Unterschiede zwischen der Bearbeitung mit kurzen Pulsen und ultrakurzen Laserpulsen. W��hrend bei der Bearbeitung mit kurzen Laserpulsen die Ablationseffizienz mit zunehmender Oberfl��chenrauheit steigt, zeigen ultrakurze Laserpulse ein anderes Verhalten. Es konnten zwei Regime identifiziert werden. So wurde in einem ersten Bereich eine Abnahme der Ablationseffizienz bis zu einer gewissen Rauheit festgestellt, bevor wieder eine Zunahme der Effizienz stattfindet. Weiterhin l��sst sich eine Abh��ngigkeit der Ablationseffizienz von der Einzelpulsenergie bzw. der mittleren Leistung bei konstanter Repetitionsrate erkennen., Laser ablation is gaining importance in the areas of research and industrial manufacturing concerning micro machining technologies. In particular, for industrial applications the process efficiency is an important factor in addition to the achievable accuracy. Most investigations in research according the ablation efficiency are done with polished surfaces samples. The aim of this work is to investigate the ablation efficiency of metals during processing with pulsed laser radiation as a function of the surface roughness. First results show differences between laser ablation with short pulses and ultrashort laser pulses. While the ablation efficiency increases with an increasing surface roughness for short laser pulses, ultrashort laser pulses show a different behaviour. Here, two regimes could be identified. In the first regime, a decrease in ablation efficiency was observed up to a certain roughness, before an increase in efficiency takes place again. Further, we observed a dependency between the maximum achievable ablation efficiency and the adjusted single pulse energy, respectively average laser power at a fixed pulse repetition rate.
Published: 2021
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40. Additional file 1 of Treatment strategies for new onset atrial fibrillation in patients treated on an intensive care unit: a systematic scoping review

Author: Drikite, Laura, Bedford, Jonathan P., O’Bryan, Liam, Petrinic, Tatjana, Rajappan, Kim, Doidge, James, Harrison, David A., Rowan, Kathryn M., Mouncey, Paul R., Young, Duncan, Watkinson, Peter J., and Corbett, Mark
Abstract: Additional file 1. Search strategy; detailed tables of studies by study design; critical appraisal; summary of reviews, surveys and opinion pieces; list of excluded studies.
Published: 2021
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41. sj-pdf-1-inc-10.1177_17511437211047180 �� Supplemental Material for Timing and burden of persistent critical illnessin UK intensive care units: An observational cohort study

Author: Harrison, David A, Creagh-Brown, Ben C, and Rowan, Kathryn M
Subjects: 111708 Health and Community Services, FOS: Clinical medicine, Cardiology, 110323 Surgery, FOS: Health sciences, 110305 Emergency Medicine
Abstract: Supplemental Material, sj-pdf-1-inc-10.1177_17511437211047180 for Timing and burden of persistent critical illnessin UK intensive care units: An observational cohort study by David A Harrison, Ben C Creagh-Brown and Kathryn M Rowan in Journal of the Intensive Care Society
Published: 2021
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42. Genetic mechanisms of critical illness in COVID-19

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Andy, Law, J Kenneth Baillie, Trevor, Paterson, Tony, Wackett, Ruth, Armstrong, Richard, Clark, Audrey, Coutts, Lorna, Donnelly, Tammy, Gilchrist, Katarzyna, Hafezi, Louise, Macgillivray, Alan, Maclean, Sarah, Mccafferty, Kirstie, Morrice, Jane, Weaver, Ceilia, Boz, Ailsa, Golightly, Mari, Ward, Hanning, Mal, Helen, Szoor-McElhinney, Adam, Brown, Ross, Hendry, Andrew, Stenhouse, Louise, Cullum, Dawn, Law, Sarah, Law, Rachel, Law, Maaike, Swets, Nicky, Day, Filip, Taneski, Esther, Duncan, Nicholas, Parkinson, Collier, D, Wood, S, Zak, A, Borra, C, Matharu, M, May, P, Alldis, Z, Mitchelmore, O, Bowles, R, Easthope, A, Bibi, F, Lancoma-Malcolm, I, Gurasashvili, J, Pheby, J, Shiel, J, Bolton, M, Patel, M, Taylor, M, Zongo, O, Ebano, P, Harding, P, Astin-Chamberlain, R, Choudhury, Y, Cox, A, Kallon, D, Burton, M, Hall, R, Blowes, S, Prime, Z, Biddle, J, Prysyazhna, O, Newman, T, Tierney, C, Kassam, J, Shankar-Hari, M, Ostermann, M, Campos, S, Bociek, A, Lim, R, Grau, N, O Jones, T, Whitton, 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Konrad [0000-0002-0010-370X], Walker, Susan [0000-0002-5016-6426], Fourman, Max Head [0000-0001-7381-2278], Russell, Clark D [0000-0002-9873-8243], Gountouna, Elvina [0000-0001-7870-2780], Wang, Bo [0000-0002-1580-797X], Wu, Yang [0000-0002-0128-7280], Kousathanas, Athanasios [0000-0001-6265-6521], Moutsianas, Loukas [0000-0001-5453-345X], Zhai, Ranran [0000-0002-5834-9120], Beale, Rupert [0000-0002-6705-8560], Keating, Sean [0000-0001-8552-5604], Haley, Chris [0000-0002-9811-0210], Porteous, David J [0000-0003-1249-6106], Hayward, Caroline [0000-0002-9405-9550], Yang, Jian [0000-0003-2001-2474], Knight, Julian [0000-0002-0377-5536], Summers, Charlotte [0000-0002-7269-2873], Shankar-Hari, Manu [0000-0002-5338-2538], Turtle, Lance [0000-0002-0778-1693], Moore, Shona C [0000-0001-8610-2806], Hinds, Charles [0000-0001-5094-8324], McAuley, Danny [0000-0002-3283-1947], Montgomery, Hugh [0000-0001-8797-5019], Renieri, Alessandra [0000-0002-0846-9220], Shen, Xia [0000-0003-4390-1979], 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T., Massey, E., Croston, G., Reschreiter, H., Camsooksai, J., Patch, S., Jenkins, S., Humphrey, C., Wadams, B., Msiska, M., Adanini, O., Attwood, B., Parsons, P., Tatham, K., Jhanji, S., Black, E., Dela Rosa, A., Howle, R., Thomas, B., Bemand, T., Raobaikady, R., Saha, R., Staines, N., Daniel, A., Finn, J., Hutter, J., Doble, P., Shovelton, C., Pawley, C., Kannan, T., Hill, M., Combes, E., Monnery, S., Joefield, T., Popescu, M., Thankachen, M., Oblak, M., Little, J., Mcivor, S., Brady, A., Whittle, H., Prady, H., Chan, R., Ahmed, A., Morris, A., Gibson, C., Gordon, E., Keenan, S., Quinn, H., Benyon, S., Marriott, S., Zitter, L., Park, L., Baines, K., Lyons, M., Holland, M., Keenan, N., Young, M., Garrioch, S., Dawson, J., Tolson, M., Scholefield, B., Bi, R., Richardson, N., Schumacher, N., Cosier, T., Millen, G., Higham, A., Turki, S., Allen, L., Crisp, N., Hazleton, T., Knight, A., Deery, J., Price, C., Turney, S., Tilbey, S., Beranova, E., Wright, D., George, L., Twiss, S., Wadd, S., Postlethwaite, K., Gondo, P., Masunda, B., Kayani, A., Hadebe, B., Whiteside, J., Clarke, N., Donnison, P., Trim, F., Leadbitter, I., Butcher, D., O'Sullivan, S., Purewal, B., Bell, S., Rivers, V., O'Leary, R., Birch, J., Collins, E., Anderson, S., Hammerton, K., Andrews, E., Burns, K., Edmond, I., Todd, A., Donnachie, J., Turner, P., Prentice, L., Symon, L., Runciman, N., Auld, F., Halkes, M., Mercer, P., Thornton, L., Debreceni, G., Wilkins, J., Crickmore, V., Subramanian, G., Marshall, R., Jennings, C., Latif, M., Bunni, L., Spivey, M., Bean, S., Burt, K., Linnett, V., Ritzema, J., Sanderson, A., Mccormick, W., Bokhari, M., Kapoor, R., Loader, D., Ayers, A., Harrison, W., North, J., Belagodu, Z., Paramsothy, R., Olufuwa, O., Gherman, A., Fuller, B., Stuart, C., Kelsall, O., Davis, C., Wild, L., Wood, H., Thrush, J., Durie, A., Austin, K., Archer, K., Anderson, P., Vigurs, C., Thorpe, C., Knights, E., Boyle, N., Price, A., Kubisz-Pudelko, A., Wood, D., Lewis, A., Board, S., Pippard, L., Perry, J., Beesley, K., Rattray, A., Lee, E., Lennon, L., Douglas, K., Bell, D., Boyle, R., Glass, L., Nauman Akhtar, M., Dent, K., Potoczna, D., Pearson, S., Horsley, E., Spencer, S., Mullan, D., Skinner, D., Gaylard, J., Barber, R., Hewitt, C., Hilldrith, A., Shepardson, S., Wills, M., Jackson-Lawrence, K., Gupta, A., Timlick, E., Gorman, C., Otahal, I., Gales, A., Coetzee, S., Sell, C., Raj, M., Peiu, M., Quaid, S., Watson, E., Elliott, K., Mallinson, J., Chandler, B., Turnbull, A., Finch, C., Holl, C., Cooper, J., Evans, A., Khaliq, W., Collins, A., Gude, E. T., Love, N., van Koutrik, L., Hunt, J., Kaye, D., Fisher, E., Brayne, A., Tuckey, V., Jackson, P., Parkin, J., Tariq, A., Houlden, H., Tucci, A., Hardy, J., Moncur, E., Highgate, J., Cowley, A., Mitra, A., Stead, R., Behan, T., Burnett, C., Newton, M., Heeney, E., Pollard, R., Hatton, J., Patel, A., Kasipandian, V., Allibone, S., Genetu, R. M., O'Brien, L., Omar, Z., Perkins, E., Davies, K., Tetla, D., Shelley, B., Irvine, V., Williams, S., Williams, P., Goodsell, J., Tutton, R., Bough, L., Winter-Goodwin, B., Kitson, R., Pinnell, J., Wilson, A., Nortcliffe, T., Wood, T., Home, M., Holdroyd, K., Robinson, M., Shaw, R., Greig, J., Brady, M., Haigh, A., Matupe, L., Usher, M., Mellor, S., Dale, S., Gledhill, L., Shaw, L., Turner, G., Kelly, D., Anwar, B., Riley, H., Sturgeon, H., Ali, A., Thomis, L., Melia, D., Dance, A., Humphreys, S., Frost, I., Gopal, V., Godden, J., Holden, A., Swann, S., Smith, T., Clapham, M., Poultney, U., Harper, R., Rice, P., Reece-Anthony, R., Gurung, B., Moultrie, S., Odam, M., Mayer, A., Bellini, A., Pickard, A., Bryant, J., Roe, N., Sowter, J., Lang, K., Taylor, J., Barry, P., Hobrok, M., Tench, H., Wolf-Roberts, R., Mcguinness, H., Loosley, R., Hawcutt, D., Rad, L., O'Malley, L., Saunderson, P., Seddon, G., Anderson, T., Rogers, N., Ruddy, J., Harkins, M., Beith, C., Mcalpine, A., Ferguson, L., Grant, P., Macfadyen, S., Mclaughlin, M., Baird, T., Rundell, S., Welsh, B., Hamill, R., Fisher, F., Gregory, J., Campbell, A., Smuts, S., Kenneth Baillie, J., Carson, G., Alex, B., Bach, B., Barclay, W. S., Bogaert, D., Chand, M., Cooke, G. S., Docherty, A. B., Dunning, J., da Silva Filipe, A., Fletcher, T., Green, C. A., Harrison, E. M., Hiscox, J. A., Ho, A. Y. W., Horby, P. W., Ijaz, S., Khoo, S., Lim, W. S., Mentzer, A. J., Merson, L., Meynert, A. M., Noursadeghi, M., Palmarini, M., Paxton, W. A., Pollakis, G., Price, N., Rambaut, A., Robertson, D. L., Sancho-Shimizu, V., Scott, J. T., de Silva, T., Sigfrid, L., Solomon, T., Sriskandan, S., Stuart, D., Tedder, R. S., Thomson, E. C., Thompson, A. A. R., Thwaites, R. S., Turtle, L. C. W., Zambon, M., Hardwick, H., Donohue, C., Lyons, R., Norman, L., Pius, R., Drake, T. M., Fairfield, C. J., Knight, S. R., Mclean, K. A., Murphy, D., Shaw, C. A., Dalton, J., Girvan, M., Saviciute, E., Roberts, S., Harrison, J., Marsh, L., Connor, M., Halpin, S., Gamble, C., Leeming, G., Wham, M., Greenhalf, W., Shaw, V., Mcdonald, S., Ganna, A., Sulem, P., van Heel, D. A., Cordioli, M., Sveinbjornsson, G., Niemi, M. E. K., Shelton, J. F., Shastri, A. J., Ye, C., Weldon, C. H., Filshtein-Sonmez, T., Coker, D., Symons, A., Esparza-Gordillo, J., Aslibekyan, S., Auton, A., Krieger, J. E., Marques, E., Jannes, C. E., Mari, F., Daga, S., Baldassarri, M., Benetti, E., Furini, S., Fallerini, C., Fava, F., Valentino, F., Doddato, G., Giliberti, A., Tita, R., Amitrano, S., Bruttini, M., Croci, S., Meloni, I., Pinto, A. M., Frullanti, E., Mencarelli, M. A., Rizzo, C. L., Montagnani, F., Di Sarno, L., Tommasi, A., Palmieri, M., Emiliozzi, A., Fabbiani, M., Rossetti, B., Zanelli, G., Bargagli, E., Bergantini, L., D'Alessandro, M., Cameli, P., Bennet, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, F., Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Spertilli, C., Feri, M., Donati, A., Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Spagnesi, M., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Ognibene, A., Vaghi, M., D'Arminio Monforte, A., Merlini, E., Mondelli, M. U., Mantovani, S., Ludovisi, S., Girardis, M., Venturelli, S., Sita, M., Cossarizza, A., Antinori, A., Vergori, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Scotton, P. G., Andretta, F., Panese, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, M. E., Magro, P., Zanella, I., Della Monica, M., Piscopo, C., Capasso, M., Russo, R., Andolfo, I., Iolascon, A., Fiorentino, G., Carella, M., Castori, M., Merla, G., Aucella, F., Raggi, P., Marciano, C., Perna, R., Bassetti, M., Di Biagio, A., Sanguinetti, M., Masucci, L., Valente, S., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Baratti, S., Trotta, T., Giannattasio, F., Coiro, G., Lena, F., Coviello, D. A., Mussini, C., Bosio, G., Martinelli, E., Mancarella, S., Tavecchia, L., Crotti, L., Picchiotti, N., Gori, M., Gabbi, C., Sanarico, M., Ceri, S., Pinoli, P., Raimondi, F., Biscarini, F., Stella, A., Shen, X., Ponting, C. P., Fawkes, A., Tenesa, A., Caulfield, M., Scott, R., Rowan, K., Murphy, L., Openshaw, P. J. M., Semple, M. G., Vitart, V., and Wilson, J. F.
Subjects: 0301 basic medicine, Male, CCR2, Chromosomes, Human, Pair 21, Genome-wide association study, Receptor, Interferon alpha-beta, Disease, Bioinformatics, Genome-wide association studies, 23andMe Investigators, Interferon alpha-beta, 0302 clinical medicine, Receptors, 2',5'-Oligoadenylate Synthetase, Pair 12, genetics, Lung, BRACOVID Investigators, Multidisciplinary, GenOMICC Investigators, Tyrosine kinase 2, 030220 oncology & carcinogenesis, Multigene Family, Medical genetics, Female, Dipeptidyl-Peptidases and Tripeptidyl-Peptidase, 5'-Oligoadenylate Synthetase, Human, Receptor, medicine.medical_specialty, Critical Care, Receptors, CCR2, General Science & Technology, Critical Illness, Chromosomes, 03 medical and health sciences, Intensive care, Mendelian randomization, Immunogenetics, medicine, Humans, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Gen-COVID Investigators, Inflammation, TYK2 Kinase, Chromosomes, Human, Pair 12, Pair 19, SARS-CoV-2, business.industry, Drug Repositioning, COVID-19, United Kingdom, COVID-19 Human Genetics Initiative, 030104 developmental biology, Viral infection, Chromosomes, Human, Pair 19, Genome-Wide Association Study, Pharmacogenomics, ISARICC Investigators, Pair 21, 2', business
Abstract: Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079,P=1.65×10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1,OAS2andOAS3); on chromosome 19p13.2 (rs74956615,P=2.3×10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069,P=3.98× 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757,P=4.99×10−8) in the interferon receptor geneIFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression ofIFNAR2, or high expression ofTYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptorCCR2is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice.
Published: 2020
Full Text: View/download PDF

43. Looking ahead

Author: Harrison, David
Published: 2020
Full Text: View/download PDF

44. Regulatory Science Education: The Need for Generalization

Author: Moghissi, Alan, Calderone, Richard, Auffret, Jean Pierre, Jaeger, Lisa, Longstreth, Janice, McBride, Dennis, Steen, Tomoko, Harrison, David, Garrison, Destini, McDaniel, Natalie, Debrah, Henry, Gloutak, Larissa, Shumway, Douglas, Turner, Deniek, Woolley, Griffin, and Washington, Kerra
Subjects: regulatory affairs education, regulatory science, regulatory science education
Abstract: Ever since the beginning of regulatory science, the need for relevant education has been recognized. However, after the Food and Drug Administration (FDA) officially recognized regulatory science, several universities have developed educational programs. This paper provides the results of a study to evaluate the existing education programs on regulatory science. The study identifies the generic definition of regulatory science, consisting of applied version of various scientific disciplines used in the regulatory process. The study found that the educational programs in regulatory science largely dealt with compliance with FDA regulations. In many cases, the programs used the term "regulatory affairs" to describe the regulations and how to comply with them. Based on the experience at Georgetown University, the study provides an outline for regulatory science education. The proposed educational program consists of: 1) approximately 10 topics that are relevant to most, if not all, regulatory science disciplines; 2) a summary of various regulatory science disciplines; and 3) education in specific regulatory science disciplines. https://doi.org/10.21423/jrs-v08moghissi, Journal of Regulatory Science, Vol. 8 (2020)
Published: 2020
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45. A new look at the mosaic theory of hypertension

Author: Touyz, Rhian M., Feldman, Ross D., Harrison, David G., and Schiffrin, Ernesto L.
Abstract: No abstract available.
Published: 2020

46. Ag2S nanodots for advanced biological applications through Luminescence Thermometry and Fluorescence Images

Author: Assis Santos, Harrison David, Jaque García, Daniel, Silva, Carlos Jacinto da, UAM. Departamento de Física de Materiales, Jaque García, Daniel (dir.), and Silva, Carlos Jacinto da (dir.)
Subjects: Materiales nanoestructurados - Propiedades - Tesis doctorales, Física, Materiales nanoestructurados - Uso terapéutico - Tesis doctorales
Abstract: Tesis doctoral inédita cotutelada por la Universidade Federal de Alagoas de Brasil y la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Física de Materiales. Fecha de lectura: 13-03-2020
Published: 2020

47. sj-pdf-2-inc-10.1177_1751143720949458 - Supplemental material for Airway management during in-hospital cardiac arrest in adults: UK national survey and interview study with anaesthetic and intensive care trainees

Author: Goodwin, Laura, Samuel, Katie, Behnaz Schofield, Voss, Sarah, Brett, Stephen J, Couper, Keith, Gould, Doug, Harrison, David, Lall, Ranjit, Nolan, Jerry P, Perkins, Gavin D, Jasmeet Soar, Thomas, Matthew, and Benger, Jonathan
Subjects: 111708 Health and Community Services, FOS: Clinical medicine, Cardiology, 110323 Surgery, FOS: Health sciences, 110305 Emergency Medicine
Abstract: Supplemental material, sj-pdf-2-inc-10.1177_1751143720949458 for Airway management during in-hospital cardiac arrest in adults: UK national survey and interview study with anaesthetic and intensive care trainees by Laura Goodwin, Katie Samuel, Behnaz Schofield, Sarah Voss, Stephen J Brett, Keith Couper, Doug Gould, David Harrison, Ranjit Lall, Jerry P Nolan, Gavin D Perkins, Jasmeet Soar, Matthew Thomas, Jonathan Benger and in collaboration with the Research and Audit Federation of Trainees (RAFT) network: on behalf of the UCC-SMART Study Group in Journal of the Intensive Care Society
Published: 2020
Full Text: View/download PDF

48. sj-pdf-3-inc-10.1177_1751143720949458 - Supplemental material for Airway management during in-hospital cardiac arrest in adults: UK national survey and interview study with anaesthetic and intensive care trainees

Author: Goodwin, Laura, Samuel, Katie, Behnaz Schofield, Voss, Sarah, Brett, Stephen J, Couper, Keith, Gould, Doug, Harrison, David, Lall, Ranjit, Nolan, Jerry P, Perkins, Gavin D, Jasmeet Soar, Thomas, Matthew, and Benger, Jonathan
Subjects: 111708 Health and Community Services, FOS: Clinical medicine, Cardiology, 110323 Surgery, FOS: Health sciences, 110305 Emergency Medicine
Abstract: Supplemental material, sj-pdf-3-inc-10.1177_1751143720949458 for Airway management during in-hospital cardiac arrest in adults: UK national survey and interview study with anaesthetic and intensive care trainees by Laura Goodwin, Katie Samuel, Behnaz Schofield, Sarah Voss, Stephen J Brett, Keith Couper, Doug Gould, David Harrison, Ranjit Lall, Jerry P Nolan, Gavin D Perkins, Jasmeet Soar, Matthew Thomas, Jonathan Benger and in collaboration with the Research and Audit Federation of Trainees (RAFT) network: on behalf of the UCC-SMART Study Group in Journal of the Intensive Care Society
Published: 2020
Full Text: View/download PDF

49. Additional file 2 of Type of Track and Trigger system and incidence of in-hospital cardiac arrest: an observational registry-based study

Author: Hogan, Helen, Hutchings, Andrew, Wulff, Jerome, Carver, Catherine, Holdsworth, Elizabeth, Nolan, Jerry, Welch, John, Harrison, David, and Black, Nick
Abstract: Additional file 2 : Table S2. Comparison of the hospitals included in final sample with those excluded and all hospitals in the National Cardiac Arrest Audit.
Published: 2020
Full Text: View/download PDF

50. sj-pdf-2-inc-10.1177_1751143720949458 - Supplemental material for Airway management during in-hospital cardiac arrest in adults: UK national survey and interview study with anaesthetic and intensive care trainees

Author: Goodwin, Laura, Samuel, Katie, Behnaz Schofield, Voss, Sarah, Brett, Stephen J, Couper, Keith, Gould, Doug, Harrison, David, Lall, Ranjit, Nolan, Jerry P, Perkins, Gavin D, Jasmeet Soar, Thomas, Matthew, and Benger, Jonathan
Subjects: 111708 Health and Community Services, FOS: Clinical medicine, Cardiology, 110323 Surgery, FOS: Health sciences, 110305 Emergency Medicine
Abstract: Supplemental material, sj-pdf-2-inc-10.1177_1751143720949458 for Airway management during in-hospital cardiac arrest in adults: UK national survey and interview study with anaesthetic and intensive care trainees by Laura Goodwin, Katie Samuel, Behnaz Schofield, Sarah Voss, Stephen J Brett, Keith Couper, Doug Gould, David Harrison, Ranjit Lall, Jerry P Nolan, Gavin D Perkins, Jasmeet Soar, Matthew Thomas, Jonathan Benger and in collaboration with the Research and Audit Federation of Trainees (RAFT) network: on behalf of the UCC-SMART Study Group in Journal of the Intensive Care Society
Published: 2020
Full Text: View/download PDF

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