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2. Photoluminescence mapping of laser-damaged β-Ga2O3

Author

Huso, Jesse, primary, McCluskey, Matthew D., additional, McCloy, John S., additional, Bhattacharyya, Arkka, additional, Krishnamoorthy, Sriram, additional, Frye, Clint D., additional, Varley, Joel B., additional, and Voss, Lars F., additional

Published
2024
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4. Synthesis and preclinical evaluation of [11C]EAI045 as a PET tracer for imaging tumors expressing mutated epidermal growth factor receptor

Author

Högnäsbacka, Antonia A., primary, Poot, Alex J., additional, Plisson, Christophe, additional, Bergare, Jonas, additional, Bonsall, David R., additional, McCluskey, Stuart P., additional, Wells, Lisa A., additional, Kooijman, Esther, additional, Schuit, Robert C., additional, Verlaan, Mariska, additional, Beaino, Wissam, additional, van Dongen, Guus A. M. S., additional, Vugts, Danielle J., additional, Elmore, Charles S., additional, Passchier, Jan, additional, and Windhorst, Albert D., additional

Published
2024
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5. Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche

Author

Dawson, Amy, primary, Zarou, Martha M., additional, Prasad, Bodhayan, additional, Bittencourt-Silvestre, Joana, additional, Zerbst, Désirée, additional, Himonas, Ekaterini, additional, Hsieh, Ya-Ching, additional, van Loon, Isabel, additional, Blanco, Giovanny Rodriguez, additional, Ianniciello, Angela, additional, Kerekes, Zsombor, additional, Krishnan, Vaidehi, additional, Agarwal, Puneet, additional, Almasoudi, Hassan, additional, McCluskey, Laura, additional, Hopcroft, Lisa E. M., additional, Scott, Mary T., additional, Baquero, Pablo, additional, Dunn, Karen, additional, Vetrie, David, additional, Copland, Mhairi, additional, Bhatia, Ravi, additional, Coffelt, Seth B., additional, Tiong, Ong Sin, additional, Wheadon, Helen, additional, Zanivan, Sara, additional, Kirschner, Kristina, additional, and Helgason, G. Vignir, additional

Published
2024
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6. Single-cell analysis of psoriasis resolution demonstrates an inflammatory fibroblast state targeted by IL-23 blockade

Author

Francis, Luc, primary, McCluskey, Daniel, additional, Ganier, Clarisse, additional, Jiang, Treasa, additional, Du-Harpur, Xinyi, additional, Gabriel, Jeyrroy, additional, Dhami, Pawan, additional, Kamra, Yogesh, additional, Visvanathan, Sudha, additional, Barker, Jonathan N., additional, Smith, Catherine H., additional, Capon, Francesca, additional, and Mahil, Satveer K., additional

Published
2024
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9. Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Author

Faheem, Waleed, Nandra, Taran, Richardson, Sarah, Saliu, David, Wilson, Daisy, Jackson, Thomas A., Magill, Laura, McCluskey, Lauren, Perry, Rita, Welch, Carly, Copeland, Claire, Cunningham, Emma L., Davis, Daniel, Treml, Jonathan, Pinkney, Thomas, Quinn, Terrence, Nightingale, Peter, Jelley, Benjamin, Gaunt, Victoria, Lochlainn, Mary Ni, Giridharan, Kumudhini, Alsahab, Mustafa, Makin, Stephen, Torsney, Kelli, Masoli, Jane, Ronan, Lindsay, Burton, Jenni K., Todd, Oliver, Taylor, Joanne, Willott, Ruth, Cox, Natalie, Healy, Roisin, Haddad, Nedaa, Ramakrishna, Sharan, Subhan, Zahid, Mazzoleni, Antonella, Nynaes, Olga, Crofts, Jodie, McNicholas, Emily, Baillie, Jonathan, Irwin, Sophie J., Kelly, Dominic, Leah, Eleanor, Evans, Jenny, Bowman, Mark A., Quinn, Sinead, Wilson, Joseph B., Hughes, Clare, and Moore, Emily

Subjects
Recognition, Frailty, Delirium, General Medicine, Mortality, Geriatrics and Gerontology, Gerontology
Abstract

Purpose Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes.

Published
2023

11. Determinants of health-related quality of life in people with Human Immunodeficiency Virus, failing first-line treatment in Africa

Author

Rautenberg, Tamlyn A., primary, Ng, Shu Kay, additional, George, Gavin, additional, Moosa, Mahomed-Yunus S., additional, McCluskey, Suzanne M., additional, Gilbert, Rebecca F., additional, Pillay, Selvan, additional, Aturinda, Isaac, additional, Ard, Kevin L., additional, Muyindike, Winnie R., additional, Musinguzi, Nicholas, additional, Masette, Godfrey, additional, Pillay, Melendhran, additional, Moodley, Pravi, additional, Brijkumar, Jaysingh, additional, Gandhi, Rajesh T., additional, Johnson, Brent, additional, Sunpath, Henry, additional, Bwana, Mwebesa B., additional, Marconi, Vincent C., additional, and Siedner, Mark J., additional

Published
2023
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14. Adolescent Mental Health Priorities During the Covid-19 Pandemic

Author

Tracy M. Stewart, Debi Fry, Jenny Wilson, Lesley McAra, Sarah Hamilton, Albert King, Margaret Laurie, and Gillean McCluskey

Subjects
wellbeing, school, Developmental and Educational Psychology, adolescents, Covid-19, mental health, Education
Abstract

Increasing evidence has shown that the Covid-19 outbreak has impacted adolescents’ mental health. Utilising a mixed-method design, the current study examined a total of 518 adolescent perspectives (60% female), in Scotland, on what has and could help their mental health in the context of Covid-19. A reflexive thematic analysis revealed three themes in relation to what has helped adolescents’ mental health since the Covid-19 outbreak. These related to findings about the value of: (1) engaging in recreational activities, (2) engaging with friends, and (3) the disruption to schooling. The remaining four themes related to what could have helped adolescents mental health and wellbeing since the Covid-19 outbreak. These focussed on (1) better support: in relation to mental health; school work; and communication, (2) contact with friends, and (3) more opportunities for recreational activities. Males were more likely to report recreational activities had helped and less likely to report better support could have helped. Adolescents who reached clinical threshold for depression and anxiety and those with elevated PTSD-like symptoms about Covid-19 were more likely to state more support could have helped, and adolescents who reached clinical threshold for depression were less likely to report that friends could have helped their mental health. The findings may inform mental health policy and interventions in the recovery from the Covid-19 pandemic.

Published
2022

15. Investigating TSPO levels in occupation-related posttraumatic stress disorder

Author

Watling, Sarah E., primary, Gill, Talwinder, additional, Gaudette, Erin V., additional, Richardson, J. Don, additional, McCluskey, Tina, additional, Tong, Junchao, additional, Meyer, Jeffrey H., additional, Warsh, Jerry, additional, Jetly, Rakesh, additional, Hutchison, Michael G., additional, Rhind, Shawn G., additional, Houle, Sylvain, additional, Kish, Stephen J., additional, and Boileau, Isabelle, additional

Published
2023
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17. Investigating TSPO levels in occupation-related posttraumatic stress disorder

Author

Sarah E. Watling, Talwinder Gill, Erin V. Gaudette, J. Don Richardson, Tina McCluskey, Junchao Tong, Jeffrey H. Meyer, Jerry Warsh, Rakesh Jetly, Michael G. Hutchison, Shawn G. Rhind, Sylvain Houle, Stephen J. Kish, and Isabelle Boileau

Subjects
Multidisciplinary
Abstract

Microglia are immune brain cells implicated in stress-related mental illnesses including posttraumatic stress disorder (PTSD). Their role in the pathophysiology of PTSD, and on neurobiological systems that regulate stress, is not completely understood. We tested the hypothesis that microglia activation, in fronto-limbic brain regions involved in PTSD, would be elevated in participants with occupation-related PTSD. We also explored the relationship between cortisol and microglia activation. Twenty participants with PTSD and 23 healthy controls (HC) completed positron emission tomography (PET) scanning of the 18-kDa translocator protein (TSPO), a putative biomarker of microglia activation using the probe [18F]FEPPA, and blood samples for measurement of cortisol. [18F]FEPPA VT was non-significantly elevated (6.5–30%) in fronto-limbic regions in PTSD participants. [18F]FEPPA VT was significantly higher in PTSD participants reporting frequent cannabis use compared to PTSD non-users (44%, p = 0.047). Male participants with PTSD (21%, p = 0.094) and a history of early childhood trauma (33%, p = 0.116) had non-significantly higher [18F]FEPPA VT. Average fronto-limbic [18F]FEPPA VT was positively related to cortisol (r = 0.530, p = 0.028) in the PTSD group only. Although we did not find a significant abnormality in TSPO binding in PTSD, findings suggest microglial activation might have occurred in a subgroup who reported frequent cannabis use. The relationship between cortisol and TSPO binding suggests a potential link between hypothalamic–pituitary–adrenal-axis dysregulation and central immune response to trauma which warrants further study.

Published
2023

18. The role of movement in young children’s spatial experiences: a review of early childhood mathematics education research

Author

Catherine McCluskey, Anna Kilderry, Joanne Mulligan, and Virginia Kinnear

Subjects
General Mathematics, Education
Abstract

Young children’s spatial reasoning is critical to mathematics learning from an early age. Recent reviews have drawn attention to the importance of mathematical experiences in the early years; however, an explicit focus on research in spatial reasoning can contribute to a more coherent account of the field. This paper reports a scoping review of qualitative studies (n = 37) during the years 2009–2021. The studies analysed in this review provide insight into children’s embodied spatial concepts and non-verbal expressions such as gesture and the relationship between spatial reasoning and mathematics learning in early childhood (birth to 8 years). Four main themes were found: (i) children’s manipulation and transformation of objects, (ii) children’s bodily engagement with and within spaces, (iii) children’s representation and interpretation of spatial experiences, and (iv) contexts for spatial learning. While the review illuminates a deeper awareness and a more holistic and embodied view of children’s spatial competencies, there remains few studies focussed on children under three years of age. Future directions for ongoing research are identified.

Published
2023

20. Cost-Effectiveness of Constraint-Induced Movement Therapy Implementation in Neurorehabilitation: The ACTIveARM Project

Author

Lauren J. Christie, Nicola Fearn, Annie McCluskey, Meryl Lovarini, Reem Rendell, and Alison Pearce

Subjects
Pharmacology, Health Policy, Pharmacology (medical)
Abstract

Constraint-induced movement therapy (CIMT) is a recommended intervention for improving arm recovery following stroke and traumatic brain injury; however, delivery in practice remains rare.The aim of this study was to investigate the costs and cost effectiveness of CIMT delivery, and the use of a CIMT implementation package designed to improve CIMT uptake and delivery by therapists in Sydney, Australia.This economic evaluation was conducted with a subset of CIMT programmes (n = 20) delivered by neurological rehabilitation teams at five varied hospitals within a mixed methods implementation study (ACTIveARM). The costs of delivering the CIMT implementation package and publicly funded CIMT were calculated using a bottom-up approach. A cost-effectiveness analysis was conducted, using decision analytic modelling. We compared the uptake and outcomes of people who received CIMT from health services that had received a CIMT implementation package, with those receiving standard upper limb therapy. An Australian health care system perspective was used in the model, over a 3-week time horizon (the average timeframe of a CIMT programme). All costs were calculated in Australian dollars (AUD). Inputs were derived from the ACTIveARM study and relevant literature. The Action Research Arm Test was used to measure arm outcomes. Sensitivity analyses assessed the impact of improving CIMT uptake, scale-up of the implementation package and resource adjustment, including a 'best-case' scenario analysis.The total cost of delivering the implementation package to nine teams across five hospitals was $110,336.43 AUD over 18 months. The mean cost of delivering an individual CIMT programme was $1233.38 AUD per participant, and $936.03 AUD per participant for group-based programmes. The incremental cost-effectiveness ratio (ICER) of individual CIMT programmes was $8052 AUD per additional person achieving meaningful improvement in arm function, and $6045 AUD for group-based CIMT. The ICER was most sensitive to reductions in staffing costs. In the 'best-case' scenario, the ICER for both individual and group-based CIMT was $245 AUD per additional person gaining a meaningful change in function.Therapists improved CIMT uptake and delivery with the support of an implementation package, however cost effectiveness was unclear.https://anzctr.org.au/Trial ID: ACTRN12617001147370.

Published
2022

22. RIPK3 controls MAIT cell accumulation during development but not during infection

Author

Patton, Timothy, primary, Zhao, Zhe, additional, Lim, Xin Yi, additional, Eddy, Eleanor, additional, Wang, Huimeng, additional, Nelson, Adam G., additional, Ennis, Bronte, additional, Eckle, Sidonia B. G., additional, Souter, Michael N. T., additional, Pediongco, Troi J., additional, Koay, Hui-Fern, additional, Zhang, Jian-Guo, additional, Djajawi, Tirta M., additional, Louis, Cynthia, additional, Lalaoui, Najoua, additional, Jacquelot, Nicolas, additional, Lew, Andrew M., additional, Pellicci, Daniel G., additional, McCluskey, James, additional, Zhan, Yifan, additional, Chen, Zhenjun, additional, Lawlor, Kate E., additional, and Corbett, Alexandra J., additional

Published
2023
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26. A versatile multimodal chromatography strategy to rapidly purify protein nanostructures assembled in cell lysates

Author

Daniel L. Winter, Hélène Lebhar, Joshua B. McCluskey, and Dominic J. Glover

Subjects
Biomedical Engineering, Pharmaceutical Science, Molecular Medicine, Medicine (miscellaneous), Bioengineering, Applied Microbiology and Biotechnology
Abstract

Background Protein nanostructures produced through the self-assembly of individual subunits are attractive scaffolds to attach and position functional molecules for applications in biomaterials, metabolic engineering, tissue engineering, and a plethora of nanomaterials. However, the assembly of multicomponent protein nanomaterials is generally a laborious process that requires each protein component to be separately expressed and purified prior to assembly. Moreover, excess components not incorporated into the final assembly must be removed from the solution and thereby necessitate additional processing steps. Results We developed an efficient approach to purify functionalized protein nanostructures directly from bacterial lysates through a type of multimodal chromatography (MMC) that combines size-exclusion, hydrophilic interaction, and ion exchange to separate recombinant protein assemblies from excess free subunits and bacterial proteins. We employed the ultrastable filamentous protein gamma-prefoldin as a material scaffold that can be functionalized with a variety of protein domains through SpyTag/SpyCatcher conjugation chemistry. The purification of recombinant gamma-prefoldin filaments from bacterial lysates using MMC was tested across a wide range of salt concentrations and pH, demonstrating that the MMC resin is robust, however the optimal choice of salt species, salt concentration, and pH is likely dependent on the protein nanostructure to be purified. In addition, we show that pre-processing of the samples with tangential flow filtration to remove nucleotides and metabolites improves resin capacity, and that post-processing with Triton X-114 phase partitioning is useful to remove lipids and any remaining lipid-associated protein. Subsequently, functionalized protein filaments were purified from bacterial lysates using MMC and shown to be free of unincorporated subunits. The assembly and purification of protein filaments with varying amounts of functionalization was confirmed using polyacrylamide gel electrophoresis, Förster resonance energy transfer, and transmission electron microscopy. Finally, we compared our MMC workflow to anion exchange chromatography with the purification of encapsulin nanocompartments containing a fluorescent protein as a cargo, demonstrating the versatility of the protocol and that the purity of the assembly is comparable to more traditional procedures. Conclusions We envision that the use of MMC will increase the throughput of protein nanostructure prototyping as well as enable the upscaling of the bioproduction of protein nanodevices. Graphic Abstract

Published
2023

27. RIPK3 controls MAIT cell accumulation during development but not during infection

Author

Timothy Patton, Zhe Zhao, Xin Yi Lim, Eleanor Eddy, Huimeng Wang, Adam G. Nelson, Bronte Ennis, Sidonia B. G. Eckle, Michael N. T. Souter, Troi J. Pediongco, Hui-Fern Koay, Jian-Guo Zhang, Tirta M. Djajawi, Cynthia Louis, Najoua Lalaoui, Nicolas Jacquelot, Andrew M. Lew, Daniel G. Pellicci, James McCluskey, Yifan Zhan, Zhenjun Chen, Kate E. Lawlor, and Alexandra J. Corbett

Subjects
Cancer Research, Cellular and Molecular Neuroscience, Immunology, Cell Biology
Abstract

Cell death mechanisms in T lymphocytes vary according to their developmental stage, cell subset and activation status. The cell death control mechanisms of mucosal-associated invariant T (MAIT) cells, a specialized T cell population, are largely unknown. Here we report that MAIT cells express key necroptotic machinery; receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) protein, in abundance. Despite this, we discovered that the loss of RIPK3, but not necroptotic effector MLKL or apoptotic caspase-8, specifically increased MAIT cell abundance at steady-state in the thymus, spleen, liver and lungs, in a cell-intrinsic manner. In contrast, over the course of infection with Francisella tularensis, RIPK3 deficiency did not impact the magnitude of the expansion nor contraction of MAIT cell pools. These findings suggest that, distinct from conventional T cells, the accumulation of MAIT cells is restrained by RIPK3 signalling, likely prior to thymic egress, in a manner independent of canonical apoptotic and necroptotic cell death pathways.

Published
2023

28. Fluid management for kidney transplantation: is it really about more or less?

Author

S. Joseph Kim, Paula Perez Jimenez, and Stuart A. McCluskey

Subjects
medicine.medical_specialty, Anesthesiology and Pain Medicine, business.industry, Anesthesiology, Anesthesia, Pain medicine, medicine, General Medicine, Fluid management, business, medicine.disease, Intensive care medicine, Kidney transplantation
Published
2021

30. Can you trust clinical practice guidelines for laparoscopic surgery? A systematic review of clinical practice guidelines for laparoscopic surgery

Author

Kurinchi Selvan Gurusamy, Aled McCluskey, Bo Zhen Hao, Brian R. Davidson, Kenneth Au Yeung, Jeffrey Leung, Jonathan Leong, and Yusuf Kayani

Subjects
Laparoscopic surgery, medicine.medical_specialty, business.industry, medicine.medical_treatment, Odds ratio, Guideline, Confidence interval, Rigour, Surgery, Clinical Practice, Quartile, Physical therapy, Medicine, Clinical care, business
Abstract

Background Clinical practice guidelines aim to support clinicians in providing clinical care and should be supported by evidence. There is currently no information on whether clinical practice guidelines in laparoscopic surgery are supported by evidence. Methods We performed a systematic review and identified clinical practice guidelines of laparoscopic surgery published in PubMed and Embase between March 2016 and February 2019. We performed an independent assessment of the strength of recommendation based on the evidence provided by the guideline authors. We used the ‘Appraisal of Guidelines for Research & Evaluation II’ (AGREE-II) Tool’s ‘rigour of development’, ‘clarity of presentation’, and ‘editorial independence’ domains to assess the quality of the guidelines. We performed a mixed-effects generalised linear regression modelling. Results We retrieved 63 guidelines containing 1905 guideline statements. The median proportion of ‘difference in rating’ of strength of recommendation between the guideline authors and independent assessment was 33.3% (quartiles: 18.3%, 55.8%). The ‘rigour of development’ domain score (odds ratio 0.06; 95% confidence intervals 0.01–0.48 per unit increase in rigour score; P value = 0.0071) and whether the strength of recommendation was ‘strong’ by independent evaluation (odds ratio 0.09 (95% confidence intervals 0.06–0.13; P value Conclusion A considerable proportion of guideline statements in clinical practice guidelines in laparoscopic surgery are not supported by evidence. Guideline authors systematically overrated the strength of the recommendation (i.e., even when the evidence points to weak recommendation, guideline authors made strong recommendations).

Published
2021

36. Separation of track- and shower-like energy deposits in ProtoDUNE-SP using a convolutional neural network

Author

Abed Abud, A., primary, Abi, B., additional, Acciarri, R., additional, Acero, M. A., additional, Adames, M. R., additional, Adamov, G., additional, Adamowski, M., additional, Adams, D., additional, Adinolfi, M., additional, Aduszkiewicz, A., additional, Aguilar, J., additional, Ahmad, Z., additional, Ahmed, J., additional, Aimard, B., additional, Ali-Mohammadzadeh, B., additional, Alion, T., additional, Allison, K., additional, Alonso Monsalve, S., additional, AlRashed, M., additional, Alt, C., additional, Alton, A., additional, Alvarez, R., additional, Amedo, P., additional, Anderson, J., additional, Andreopoulos, C., additional, Andreotti, M., additional, Andrews, M., additional, Andrianala, F., additional, Andringa, S., additional, Anfimov, N., additional, Ankowski, A., additional, Antoniassi, M., additional, Antonova, M., additional, Antoshkin, A., additional, Antusch, S., additional, Aranda-Fernandez, A., additional, Arellano, L., additional, Arnold, L. O., additional, Arroyave, M. A., additional, Asaadi, J., additional, Asquith, L., additional, Aurisano, A., additional, Aushev, V., additional, Autiero, D., additional, Ayala Lara, V., additional, Ayala-Torres, M., additional, Azfar, F., additional, Babicz, M., additional, Back, A., additional, Back, H., additional, Back, J. J., additional, Backhouse, C., additional, Bagaturia, I., additional, Bagby, L., additional, Balashov, N., additional, Balasubramanian, S., additional, Baldi, P., additional, Baller, B., additional, Bambah, B., additional, Barao, F., additional, Barenboim, G., additional, Barker, G., additional, Barkhouse, W., additional, Barnes, C., additional, Barr, G., additional, Barranco Monarca, J., additional, Barros, A., additional, Barros, N., additional, Barrow, J. L., additional, Basharina-Freshville, A., additional, Bashyal, A., additional, Basque, V., additional, Batchelor, C., additional, Batista das Chagas, E., additional, Battat, J., additional, Battisti, F., additional, Bay, F., additional, Bazetto, M. C. Q., additional, Bazo Alba, J., additional, Beacom, J. F., additional, Bechetoille, E., additional, Behera, B., additional, Beigbeder, C., additional, Bellantoni, L., additional, Bellettini, G., additional, Bellini, V., additional, Beltramello, O., additional, Benekos, N., additional, Benitez Montiel, C., additional, Bento Neves, F., additional, Berger, J., additional, Berkman, S., additional, Bernardini, P., additional, Berner, R. M., additional, Bersani, A., additional, Bertolucci, S., additional, Betancourt, M., additional, Betancur Rodríguez, A., additional, Bevan, A., additional, Bezawada, Y., additional, Bezerra, T. S., additional, Bhardwaj, A., additional, Bhatnagar, V., additional, Bhattacharjee, M., additional, Bhattarai, D., additional, Bhuller, S., additional, Bhuyan, B., additional, Biagi, S., additional, Bian, J., additional, Biassoni, M., additional, Biery, K., additional, Bilki, B., additional, Bishai, M., additional, Bitadze, A., additional, Blake, A., additional, Blaszczyk, F., additional, Blazey, G., additional, Blucher, E., additional, Boissevain, J., additional, Bolognesi, S., additional, Bolton, T., additional, Bomben, L., additional, Bonesini, M., additional, Bongrand, M., additional, Bonilla-Diaz, C., additional, Bonini, F., additional, Booth, A., additional, Boran, F., additional, Bordoni, S., additional, Borkum, A., additional, Bostan, N., additional, Bour, P., additional, Bourgeois, C., additional, Boyden, D., additional, Bracinik, J., additional, Braga, D., additional, Brailsford, D., additional, Branca, A., additional, Brandt, A., additional, Bremer, J., additional, Breton, D., additional, Brew, C., additional, Brice, S. J., additional, Brizzolari, C., additional, Bromberg, C., additional, Brooke, J., additional, Bross, A., additional, Brunetti, G., additional, Brunetti, M., additional, Buchanan, N., additional, Budd, H., additional, Butorov, I., additional, Cagnoli, I., additional, Cai, T., additional, Caiulo, D., additional, Calabrese, R., additional, Calafiura, P., additional, Calcutt, J., additional, Calin, M., additional, Calvez, S., additional, Calvo, E., additional, Caminata, A., additional, Campanelli, M., additional, Caratelli, D., additional, Carber, D., additional, Carceller, J., additional, Carini, G., additional, Carlus, B., additional, Carneiro, M. F., additional, Carniti, P., additional, Caro Terrazas, I., additional, Carranza, H., additional, Carroll, T., additional, Castaño Forero, J. F., additional, Castillo, A., additional, Castromonte, C., additional, Catano-Mur, E., additional, Cattadori, C., additional, Cavalier, F., additional, Cavallaro, G., additional, Cavanna, F., additional, Centro, S., additional, Cerati, G., additional, Cervelli, A., additional, Cervera Villanueva, A., additional, Chalifour, M., additional, Chappell, A., additional, Chardonnet, E., additional, Charitonidis, N., additional, Chatterjee, A., additional, Chattopadhyay, S., additional, Chavarry Neyra, M., additional, Chen, H., additional, Chen, M., additional, Chen, Y., additional, Chen, Z., additional, Chen-Wishart, Z., additional, Cheon, Y., additional, Cherdack, D., additional, Chi, C., additional, Childress, S., additional, Chirco, R., additional, Chiriacescu, A., additional, Chisnall, G., additional, Cho, K., additional, Choate, S., additional, Chokheli, D., additional, Chong, P. S., additional, Christensen, A., additional, Christian, D., additional, Christodoulou, G., additional, Chukanov, A., additional, Chung, M., additional, Church, E., additional, Cicero, V., additional, Clarke, P., additional, Cline, G., additional, Coan, T. E., additional, Cocco, A. G., additional, Coelho, J., additional, Colton, N., additional, Conley, E., additional, Conley, R., additional, Conrad, J., additional, Convery, M., additional, Copello, S., additional, Cova, P., additional, Cremaldi, L., additional, Cremonesi, L., additional, Crespo-Anadón, J. I., additional, Crisler, M., additional, Cristaldo, E., additional, Crnkovic, J., additional, Cross, R., additional, Cudd, A., additional, Cuesta, C., additional, Cui, Y., additional, Cussans, D., additional, Dalager, O., additional, Da Motta, H., additional, Da Silva Peres, L., additional, David, C., additional, David, Q., additional, Davies, G. S., additional, Davini, S., additional, Dawson, J., additional, De, K., additional, De, S., additional, Debbins, P., additional, De Bonis, I., additional, Decowski, M., additional, De Gouvea, A., additional, De Holanda, P. C., additional, De Icaza Astiz, I. L., additional, Deisting, A., additional, De Jong, P., additional, Delbart, A., additional, Delepine, D., additional, Delgado, M., additional, Dell’Acqua, A., additional, Delmonte, N., additional, De Lurgio, P., additional, De Mello Neto, J. R., additional, DeMuth, D. M., additional, Dennis, S., additional, Densham, C., additional, Deptuch, G. W., additional, De Roeck, A., additional, De Romeri, V., additional, De Souza, G., additional, Devi, R., additional, Dharmapalan, R., additional, Dias, M., additional, Diaz, F., additional, Diaz, J., additional, Di Domizio, S., additional, Di Giulio, L., additional, Ding, P., additional, Di Noto, L., additional, Dirkx, G., additional, Distefano, C., additional, Diurba, R., additional, Diwan, M., additional, Djurcic, Z., additional, Doering, D., additional, Dolan, S., additional, Dolek, F., additional, Dolinski, M., additional, Domine, L., additional, Donon, Y., additional, Douglas, D., additional, Douillet, D., additional, Dragone, A., additional, Drake, G., additional, Drielsma, F., additional, Duarte, L., additional, Duchesneau, D., additional, Duffy, K., additional, Dunne, P., additional, Dutta, B., additional, Duyang, H., additional, Dvornikov, O., additional, Dwyer, D., additional, Dyshkant, A., additional, Eads, M., additional, Earle, A., additional, Edmunds, D., additional, Eisch, J., additional, Emberger, L., additional, Emery, S., additional, Englezos, P., additional, Ereditato, A., additional, Erjavec, T., additional, Escobar, C., additional, Eurin, G., additional, Evans, J. 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Published
2022
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37. Albumin use in bleeding cardiac surgical patients and associated patient outcomes

Author

Ciara Hanley, Justyna Bartoszko, Keyvan Karkouti, Stuart A. McCluskey, and Jeannie Callum

Subjects
medicine.medical_specialty, Resuscitation, business.industry, Acute kidney injury, General Medicine, Odds ratio, Perioperative, medicine.disease, Intensive care unit, law.invention, Cardiac surgery, Anesthesiology and Pain Medicine, law, Anesthesia, Heart failure, Anesthesiology, medicine, business
Abstract

Albumin solution is a colloid used for resuscitation in cardiac surgical patients, but it is unclear if it offers advantages over crystalloids. We examined current clinical practice across 11 cardiac surgical centres and the association of albumin with outcomes in a cohort of bleeding cardiac surgical patients. This was a post hoc analysis of data from the Effect of Fibrinogen Concentrate vs Cryoprecipitate on Blood Component Transfusion After Cardiac Surgery (FIBRES) trial. Multivariable regression models adjusted for demographic and surgical characteristics were used to examine predictors of early albumin administration (within the initial 24 perioperative hours), late albumin administration (from 24 hr to seven days after cardiopulmonary bypass), and the association of albumin use with 28-day acute kidney injury, mortality, and length of hospital and intensive care unit (ICU) stay. Of the 735 patients included, 525 (71%) received albumin, ranging from 4.8% to 97.4% of patients across institutions, with 475 (64.6%) receiving albumin early (5% or 25% solution). In the adjusted models, female sex and preoperative hospital admission were associated with early use, while heart failure, female sex, bleeding severity, older age, and prior albumin use were predictors of later administration. Early albumin use was not associated with differences in acute kidney injury (adjusted odds ratio [aOR] 1.77; 95% confidence interval [CI], 0.96 to 3.27; P = 0.07), mortality (aOR 1.66; 95% CI, 0.99 to 2.78; P = 0.05), or length of ICU stay (P = 0.11) or hospital stay (P = 0.67). Albumin use is common but highly variable within and across sites. Albumin use was not associated with improved outcomes. High quality randomized controlled trials should clarify its role in cardiac surgical patients.

Published
2021

38. On the Importance of Domain Model Configuration for Automated Planning Engines

Author

Thomas Leo McCluskey, Frank Hutter, Mauro Vallati, and Lukáš Chrpa

Subjects
Online and offline, Computer science, business.industry, Distributed computing, Knowledge engineering, 020207 software engineering, 0102 computer and information sciences, 02 engineering and technology, Domain model, Modular design, 01 natural sciences, Software, Computational Theory and Mathematics, 010201 computation theory & mathematics, Artificial Intelligence, Automated planning and scheduling, 0202 electrical engineering, electronic engineering, information engineering, Domain knowledge, Macro, business
Abstract

The development of domain-independent planners within the AI planning community is leading to “off-the-shelf” technology that can be used in a wide range of applications. Moreover, it allows a modular approach—in which planners and domain knowledge are modules of larger software applications—that facilitates substitutions or improvements of individual modules without changing the rest of the system. This approach also supports the use of reformulation and configuration techniques, which transform how a model is represented in order to improve the efficiency of plan generation. In this article, we investigate how the performance of domain-independent planners is affected by domain model configuration, i.e. the order in which elements are ordered in the model, particularly in the light of planner comparisons. We then introduce techniques for the online and offline configuration of domain models, and we analyse the impact of domain model configuration on other reformulation approaches, such as macros.

Published
2021

39. Imaging the Alternatively Spliced D Domain of Tenascin C in a Preclinical Model of Inflammatory Bowel Disease

Author

Liang Zhang, Yuzhen Wang, Kristoff T. Homan, Stephanie M. Gaudette, Andrew J. McCluskey, Ying Chan, Joanne Murphy, Mary Abdalla, Christine M. Nelson, Victor Z. Sun, Jamie E. Erickson, Heather L. Knight, Anca Clabbers, Annette J. Schwartz Sterman, and Soumya Mitra

Subjects
Cancer Research, Oncology, Radiology, Nuclear Medicine and imaging
Abstract

Purpose To image colon-expressed alternatively spliced D domain of tenascin C in preclinical colitis models using near infrared (NIR)-labeled targeted molecular imaging agents. Procedures. A human IgG1 with nanomolar binding affinity specific to the alternatively spliced D domain of tenascin C was generated. Immunohistochemistry identified disease-specific expression of this extracellular matrix protein in the colon of mice given dextran sulfate sodium in the drinking water. The antibody reagent was labeled with the NIR fluorophore IRDye 800CW via amine chemistry and intravenously dosed to evaluate in vivo targeting specificity. Increasing doses of imaging agent were given to estimate the saturating dose. Results The NIR-labeled proteins successfully targeted colonic lesions in a murine model of colitis. Co-administration of a molar excess competing unlabeled dose reduced normalized uptake in diseased colon by > 70%. Near infrared ex vivo images of colon resected from diseased animals showed saturation at doses exceeding 1 nmol and was confirmed with additional quantitative ex vivo biodistribution. Cellular-level specificity and protein stability were assessed via microscopy. Conclusions Our imaging data suggest the alternatively spliced D domain of tenascin C is a promising target for delivery-based applications in inflammatory bowel diseases.

Published
2022

40. Development and interpretation of a QSAR model for in vitro breast cancer (MCF-7) cytotoxicity of 2-phenylacrylonitriles

Author

Stanton, David T., Baker, Jennifer R., McCluskey, Adam, and Paula, Stefan

Subjects
Quantitative structure–activity relationship, Cell Survival, Quantitative Structure-Activity Relationship, Antineoplastic Agents, Breast Neoplasms, 01 natural sciences, Article, Drug design, Breast cancer, 0103 physical sciences, Drug Discovery, Model interpretation, medicine, Humans, Cytotoxic T cell, MTT assay, Physical and Theoretical Chemistry, Cytotoxicity, Acrylonitrile, 010304 chemical physics, QSAR, Chemistry, Model development, medicine.disease, In vitro, 0104 chemical sciences, Computer Science Applications, 010404 medicinal & biomolecular chemistry, Receptors, Aryl Hydrocarbon, MCF-7, Cancer cell, MCF-7 Cells, Cancer research, Female, 2-phenylacrylonitriles
Abstract

The Arylhydrocarbon Receptor (AhR), a member of the Per-ARNT-SIM transcription factor family, has been as a potential new target to treat breast cancer sufferers. A series of 2-phenylacrylonitriles targeting AhR has been developed that have shown promising and selective activity against cancerous cell lines while sparing normal non-cancerous cells. A quantitative structure–activity relationship (QSAR) modeling approach was pursued in order to generate a predictive model for cytotoxicity to support ongoing synthetic activities and provide important structure-activity information for new structure design. Recent work conducted by us has identified a number of compounds that exhibited false positive cytotoxicity values in the standard MTT assay. This work describes a good quality model that not only predicts the activity of compounds in the MCF-7 breast cancer cell line, but was also able to identify structures that subsequently gave false positive values in the MTT assay by identifying compounds with aberrant biological behavior. This work not only allows the design of future breast cancer cytotoxic activity in vitro, but allows the avoidance of the synthesis of those compounds anticipated to result in anomalous cytotoxic behavior, greatly enhancing the design of such compounds. Supplementary Information The online version contains supplementary material available at 10.1007/s10822-021-00387-5.

Published
2021

41. Blood Cell Salvage and Autotransfusion Does Not Worsen Oncologic Outcomes Following Liver Transplantation with Incidental Hepatocellular Carcinoma: A Propensity Score-Matched Analysis

Author

Stuart A. McCluskey, Peter Yoon, Tommy Ivanics, Hala Muaddi, Marco P. A. W. Claasen, Christopher R Shubert, Gonzalo Sapisochin, Bettina E. Hansen, and Surgery

Subjects
medicine.medical_specialty, business.industry, medicine.medical_treatment, Hazard ratio, Intraoperative Blood Cell Salvage, Liver transplantation, medicine.disease, Gastroenterology, Confidence interval, 03 medical and health sciences, 0302 clinical medicine, Oncology, Surgical oncology, 030220 oncology & carcinogenesis, Internal medicine, Hepatocellular carcinoma, Propensity score matching, medicine, 030211 gastroenterology & hepatology, Surgery, business, Autotransfusion
Abstract

Background: Intraoperative blood cell salvage and autotransfusion (IBSA) during liver transplantation (LT) for hepatocellular carcinoma (HCC) is controversial for concern regarding adversely impacting oncologic outcomes. Objective: We aimed to evaluate the long-term oncologic outcomes of patients who underwent LT with incidentally discovered HCC who received IBSA compared with those who did not receive IBSA. Methods: Patients undergoing LT (January 2001–October 2018) with incidental HCC on explant pathology were retrospectively identified. A 1:1 propensity score matching (PSM) was performed. HCC recurrence and patient survival were compared. Kaplan–Meier survival analyses were performed, and univariable Cox proportional hazard analyses were performed for risks of recurrence and death. Results: Overall, 110 patients were identified (IBSA, n = 76 [69.1%]; non-IBSA, n = 34 [30.9%]). Before matching, the groups were similar in terms of demographics, transplant, and tumor characteristics. Overall survival was similar for IBSA and non-IBSA at 1, 3, and 5 years (96.0%, 88.4%, 83.0% vs. 97.1%, 91.1%, 87.8%, respectively; p = 0.79). Similarly, the recurrence rate at 1, 3, and 5 years was not statistically different (IBSA 0%, 1.8%, 1.8% vs. non-IBSA 0%, 3.2%, 3.2%, respectively; p = 0.55). After 1:1 matching (26 IBSA, 26 non-IBSA), Cox proportional hazard analysis demonstrated similar risk of death and recurrence between the groups (IBSA hazard ratio [HR] of death 1.26, 95% confidence interval [CI] 0.52–3.05, p = 0.61; and HR of recurrence 2.64, 95% CI 0.28–25.30, p = 0.40). Conclusions: IBSA does not appear to adversely impact oncologic outcomes in patients undergoing LT with incidental HCC. This evidence further supports the need for randomized trials evaluating the impact of IBSA use in LT for HCC.

Published
2021

42. Imaging the Alternatively Spliced D Domain of Tenascin C in a Preclinical Model of Inflammatory Bowel Disease

Author

Zhang, Liang, primary, Wang, Yuzhen, additional, Homan, Kristoff T., additional, Gaudette, Stephanie M., additional, McCluskey, Andrew J., additional, Chan, Ying, additional, Murphy, Joanne, additional, Abdalla, Mary, additional, Nelson, Christine M., additional, Sun, Victor Z., additional, Erickson, Jamie E., additional, Knight, Heather L., additional, Clabbers, Anca, additional, Sterman, Annette J. Schwartz, additional, and Mitra, Soumya, additional

Published
2022
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43. The Collaborative Ocular Tuberculosis Study (COTS) calculator—a consensus-based decision tool for initiating antitubercular therapy in ocular tuberculosis

Author

Agrawal, Rupesh, primary, Ludi, Zhang, additional, Betzler, Bjorn K., additional, Testi, Ilaria, additional, Mahajan, Sarakshi, additional, Rousellot, Andres, additional, Kempen, John H., additional, Smith, Justine R., additional, McCluskey, Peter, additional, Nguyen, Quan Dong, additional, Pavesio, Carlos, additional, and Gupta, Vishali, additional

Published
2022
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45. L’albumine pour la réanimation liquidienne chez les patients de chirurgie cardiaque : sondage auprès des fournisseurs canadiens de soins périopératoires

Author

Liu, Laura, primary, McCluskey, Stuart A., additional, Law, Michael, additional, Abrahamyan, Lusine, additional, Peer, Miki, additional, Tait, Gordon, additional, Rao, Vivek, additional, Wijeysundera, Duminda N., additional, Scales, Damon C., additional, Callum, Jeannie, additional, Karkouti, Keyvan, additional, and Bartoszko, Justyna, additional

Published
2022
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47. Differential location of NKT and MAIT cells within lymphoid tissue

Author

Johnson, Darryl N., primary, Ruan, Zheng, additional, Petley, Emma V., additional, Devi, Sapna, additional, Holz, Lauren E., additional, Uldrich, Adam P., additional, Mak, Jeffrey Y. W., additional, Hor, Jyh Liang, additional, Mueller, Scott N., additional, McCluskey, James, additional, Fairlie, David P., additional, Darcy, Phillip K., additional, Beavis, Paul A., additional, Heath, William R., additional, and Godfrey, Dale I., additional

Published
2022
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48. Experiential avoidance mediates the relation between mindfulness and anxiety

Author

Ilana Haliwa, D. Lee McCluskey, Natalie J. Shook, Jenna M. Wilson, and Jared W. Keeley

Subjects
Mediation (statistics), Mindfulness, Trait, medicine, Psychological intervention, Experiential avoidance, Anxiety, medicine.symptom, Psychology, Mental health, General Psychology, Clinical psychology
Abstract

A substantial body of evidence indicates that mindfulness is associated with less anxiety. However, less is known about the mechanisms by which mindfulness decreases anxiety. One possibility is that mindfulness encourages individuals to be less experientially avoidant (e.g., less likely to attempt to suppress or avoid unwanted private experiences), a hallmark of anxiety. The purpose of the present research was to assess whether less experiential avoidance accounted for the inverse relation between mindfulness and anxiety. Two studies were conducted with college students (Ns = 493 and 320, respectively). Participants completed self-report measures of trait mindfulness, anxiety, and experiential avoidance online (Study 1) and in person (Study 2) for course credit. Across both studies, greater mindfulness was associated with lower experiential avoidance and anxiety, and experiential avoidance was positively associated with anxiety. Furthermore, experiential avoidance significantly accounted for the relation between mindfulness and anxiety in both studies. Alternative mediation models were also tested. These findings suggest that mindfulness may improve anxiety through its effects on experiential avoidance. Given that experiential avoidance is thought to be involved in the development and maintenance of several psychological disorders, interventions involving mindfulness training may have promising broad mental health benefits. However, further research is needed to replicate these findings across clinical populations and therapeutic settings.

Published
2020

49. The molecular basis underpinning the potency and specificity of MAIT cell antigens

Author

Alexandra J. Corbett, Ligong Liu, Jamie Rossjohn, Weijun Xu, Jeffrey Y. W. Mak, James McCluskey, Wael Awad, Xin Yi Lim, Jérôme Le Nours, David P. Fairlie, Geraldine J. M. Ler, Andrew N. Keller, and Sidonia B G Eckle

Subjects
0301 basic medicine, Cellular immunity, Receptors, Antigen, T-Cell, alpha-beta, Riboflavin, T cell, Immunology, Mucosal associated invariant T cell, Ligands, Lymphocyte Activation, Major histocompatibility complex, Mucosal-Associated Invariant T Cells, Jurkat Cells, 03 medical and health sciences, 0302 clinical medicine, Antigen, Cell Line, Tumor, medicine, Humans, Immunology and Allergy, Antigens, biology, Chemistry, Antigen processing, T-cell receptor, Cell biology, 030104 developmental biology, medicine.anatomical_structure, biology.protein, Cell activation, 030215 immunology
Abstract

Mucosal-associated invariant T (MAIT) cells are activated by microbial riboflavin-based metabolite antigens when presented by MR1. How modifications to the potent antigen 5-OP-RU affect presentation by MR1 and MAIT cell activation remains unclear. Here we design 20 derivatives, termed altered metabolite ligands (AMLs), to dissect the impact of different antigen components on the human MAIT-MR1 axis. Analysis of 11 crystal structures of MAIT T cell antigen receptor (TCR)-MR1-AML ternary complexes, along with biochemical and functional assays, shows that MR1 cell-surface upregulation is influenced by ribityl and non-ribityl components of the ligand and the hydrophobicity of the MR1-AML interface. The polar ribityl chain of the AML strongly influences MAIT cell activation potency through dynamic compensatory interactions within a MAIT TCR-MR1-AML interaction triad. We define the basis by which the MAIT TCR can differentially recognize AMLs, thereby providing insight into MAIT cell antigen specificity and potency.

Published
2020

50. Perceptions of Body-Worn Cameras: Findings from a Panel Survey of Two LAPD Divisions

Author

Mariel Shutinya, Lauren Revier, Alese Wooditch, John D. McCluskey, Shellie E. Solomon, Marc Swatt, Craig D. Uchida, and Christine Connor

Subjects
Panel survey, media_common.quotation_subject, 050901 criminology, 05 social sciences, Applied psychology, Police department, Officer, Consistency (negotiation), Software deployment, Perception, 0501 psychology and cognitive sciences, 0509 other social sciences, Psychology, Law, 050104 developmental & child psychology, media_common
Abstract

This paper examines results from two waves of officer surveys, administered before and after deployment of body-worn cameras (BWCs) in two divisions within the Los Angeles Police Department (LAPD). Officer surveys were administered in LAPD’s Mission and Newton divisions at two time points, pre-BWC deployment (August and September 2015; Wave I) and post-deployment (summer of 2016; Wave II). This fixed-sample survey contained 52 questions designed to measure officer perceptions of BWCs across a variety of domains. Questions were tailored to provide consistency across sites for comparison with other studies. Results varied by division, with Mission officers becoming more critical and Newton officers becoming slightly more supportive of BWCs over time. Similarities and differences in officer perceptions both between divisions and from pre- to post-deployment are discussed at length, as are the implications for policy and practice including obtaining organizational support and officer buy-in.

Published
2020

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