• Daily electrical activity in the master circadian clock of a diurnal mammal

      senior_editor: Dulac, Catherine; editor: Tessmar-Raible, Kristin; Bano-Otalora, Beatriz; orcid: 0000-0003-4694-9943; Moye, Matthew J; Brown, Timothy; Lucas, Robert J; orcid: 0000-0002-1088-8029; email: robert.lucas@manchester.ac.uk; Diekman, Casey O; orcid: 0000-0002-4711-1395; email: diekman@njit.edu; Belle, Mino DC; orcid: 0000-0002-4917-957X; email: M.D.C.Belle@exeter.ac.uk (eLife Sciences Publications, Ltd, 2021-11-30)
      Circadian rhythms in mammals are orchestrated by a central clock within the suprachiasmatic nuclei (SCN). Our understanding of the electrophysiological basis of SCN activity comes overwhelmingly from a small number of nocturnal rodent species, and the extent to which these are retained in day-active animals remains unclear. Here, we recorded the spontaneous and evoked electrical activity of single SCN neurons in the diurnal rodent Rhabdomys pumilio, and developed cutting-edge data assimilation and mathematical modeling approaches to uncover the underlying ionic mechanisms. As in nocturnal rodents, R. pumilio SCN neurons were more excited during daytime hours. By contrast, the evoked activity of R. pumilio neurons included a prominent suppressive response that is not present in the SCN of nocturnal rodents. Our modeling revealed and subsequent experiments confirmed transient subthreshold A-type potassium channels as the primary determinant of this response, and suggest a key role for this ionic mechanism in optimizing SCN function to accommodate R. pumilio’s diurnal niche.
    • Damage Detection in Composites By Artificial Neural Networks Trained By Using in Situ Distributed Strains

      Califano, America; orcid: 0000-0002-6344-8051; email: america.califano@gmail.com; email: america.califano@unicampania.it; Chandarana, Neha; Grassia, Luigi; D’Amore, Alberto; Soutis, Constantinos; email: constantinos.soutis@manchester.ac.uk (Springer Netherlands, 2020-08-07)
      Abstract: In this paper, a passive structural health monitoring (SHM) method capable of detecting the presence of damage in carbon fibre/epoxy composite plates is developed. The method requires the measurement of strains from the considered structure, which are used to set up, train, and test artificial neural networks (ANNs). At the end of the training phase, the networks find correlations between the given strains, which represent the ‘fingerprint’ of the structure under investigation. Changes in the distribution of these strains is captured by assessing differences in the previously identified strain correlations. If any cause generates damage that alters the strain distribution, this is considered as a reason for further detailed structural inspection. The novelty of the strain algorithm comes from its independence from both the choice of material and the loading condition. It does not require the prior knowledge of material properties based on stress-strain relationships and, as the strain correlations represent the structure and its mechanical behaviour, they are valid for the full range of operating loads. An implementation of such approach is herein presented based on the usage of a distributed optical fibre sensor that allows to obtain strain measurement with an incredibly high resolution.
    • Dance at Home for People With Parkinson's During COVID-19 and Beyond: Participation, Perceptions, and Prospects

      Bek, Judith; email: judith.bek@manchester.ac.uk; Groves, Michelle; Leventhal, David; Poliakoff, Ellen (Frontiers Media S.A., 2021-05-31)
      Emerging evidence shows that dance can provide both physical and non-physical benefits for people living with Parkinson's disease (PD). The suspension of in-person dance classes during the COVID-19 pandemic necessitated a transition to remote provision via live and recorded digital media. An online survey explored accessibility of and engagement with home-based dance programs, as well as potential benefits and processes involved in participation. The survey was co-developed by researchers and dance program providers, with input from people with PD and physiotherapists. Responses were collected from 276 individuals, including 178 current users of home-based programs, the majority of whom were participating at least once per week. Among respondents not currently using digital resources, lack of knowledge and motivation were the primary barriers. Most participants (94.9%) reported that home based practise provided some benefits, including physical (e.g., balance, posture) and non-physical (e.g., mood, confidence) improvements. Participants valued the convenience and flexibility of digital participation, but noted limitations including reductions in social interaction, support from instructors and peers, and motivation. There was a strong preference (70.8%) for continuing with home-based practise alongside in-person classes in the future. The results indicate that at-home dance is accessible and usable for people with PD, and that some of the previously-reported benefits of dance may be replicated in this context. Digital dance programs will likely remain a key element of future provision for people with PD, and the present findings will inform further development of resources and research into mechanisms and outcomes of home-based dance participation.
    • Darzi's vision becomes a reality

      Holly, Chris; University of Chester (Royal College of Midwives, 2009-12)
      This articles discusses the new webside NHS Evidence - which aims to provide easy access to a comphrehensive evidence base for healthcare professionals.
    • Data protection, information governance and the potential erosion of ethnographic methods in health care?

      Lee, Rebecca R.; orcid: 0000-0002-4559-1647; email: rebecca.lee-4@manchester.ac.uk; McDonagh, Janet E.; Farre, Albert; Peters, Sarah; Cordingley, Lis; Rapley, Tim (2021-11-23)
      Abstract: With the most recent developments to the European General Data Protection Regulations (GDPR) introduced in May 2018, the resulting legislation meant a new set of considerations for study approvers and health‐care researchers. Compared with previous legislation in the UK (The Data Protection Act, 1998), it introduced more extensive and directive principles, requiring anybody ‘processing’ personal data to specifically define how this data will be obtained, stored, used and destroyed. Importantly, it also emphasised the principle of accountability, which meant that data controllers and processors could no longer just state that they planned to adhere to lawful data protection principles, they also had to demonstrate compliance. New questions and concerns around accountability now appear to have increased levels of scrutiny in all areas of information governance (IG), especially with regards to processing confidential patient information. This article explores our experiences of gaining required ethical and regulatory approvals for an ethnographic study in a UK health‐care setting, the implications that the common law duty of confidentiality had for this research, and the ways in which IG challenges were overcome. The purpose of this article was to equip researchers embarking on similar projects to be able to navigate the potentially problematic and complex journey to approval.
    • Data-Driven Dispatching Rules Mining and Real-Time Decision-Making Methodology in Intelligent Manufacturing Shop Floor with Uncertainty

      Zhang, Liping; email: zhangliping@wust.edu.cn; Hu, Yifan; email: huyifan@wust.edu.cn; Tang, Qiuhua; email: tangqiuhua@wust.edu.cn; Li, Jie; email: jie.li-2@manchester.ac.uk; Li, Zhixiong; email: zhixiong.li@yonsei.ac.kr (MDPI, 2021-07-15)
      In modern manufacturing industry, the methods supporting real-time decision-making are the urgent requirement to response the uncertainty and complexity in intelligent production process. In this paper, a novel closed-loop scheduling framework is proposed to achieve real-time decision making by calling the appropriate data-driven dispatching rules at each rescheduling point. This framework contains four parts: offline training, online decision-making, data base and rules base. In the offline training part, the potential and appropriate dispatching rules with managers’ expectations are explored successfully by an improved gene expression program (IGEP) from the historical production data, not just the available or predictable information of the shop floor. In the online decision-making part, the intelligent shop floor will implement the scheduling scheme which is scheduled by the appropriate dispatching rules from rules base and store the production data into the data base. This approach is evaluated in a scenario of the intelligent job shop with random jobs arrival. Numerical experiments demonstrate that the proposed method outperformed the existing well-known single and combination dispatching rules or the discovered dispatching rules via metaheuristic algorithm in term of makespan, total flow time and tardiness.
    • De Quervain subacute thyroiditis.

      Mundy-Baird, George; Kyriacou, Angelos; Syed, Akheel A; email: akheel.syed@manchester.ac.uk (2021-07-05)
    • De Quervain subacute thyroiditis.

      Mundy-Baird, George; Kyriacou, Angelos; Syed, Akheel A; orcid: 0000-0001-8696-7121; email: akheel.syed@manchester.ac.uk (2021-07-01)
    • Decision making in the management of adults with malignant colorectal polyps: an exploration of the experiences of patients and clinicians

      Westwood, Clare; orcid: 0000-0001-8564-3336; Lee, Tom; McSherry, Robert; Bettany‐Saltikov, Josette; Catlow, Jamie (Wiley, 2021-05-18)
    • Decision making in the management of adults with malignant colorectal polyps: An exploration of the experiences of patients and clinicians

      Westwood, Clare; orcid: 0000-0001-8564-3336; Lee, Tom; McSherry, Robert; Bettany‐Saltikov, Josette; Catlow, Jamie (Wiley, 2021-06-16)
    • Decision making in the management of adults with malignant colorectal polyps: an exploration of the experiences of patients and clinicians.

      Westwood, Clare; orcid: 0000-0001-8564-3336; Lee, Tom; McSherry, Robert; Bettany-Saltikov, Josette; Catlow, Jamie (2021-05-18)
      A diagnosis of colorectal polyp cancer presents a treatment dilemma. The decision between segmental resection versus endoscopic surveillance is difficult due to a lack of good quality clinical evidence for either option. The aim of this study was to understand the decision making experiences of both clinicians and patients when faced with such a diagnosis. Qualitative, semi-structured interviews were undertaken with ten clinicians involved in the care of patients diagnosed with polyp cancer and five patients who had experience of a diagnosis of polyp cancer. All clinicians and patients were from four hospital Trusts across the North of England. Interviews were audio recorded, transcribed verbatim and analysed using the principles of Interpretative Phenomenological Analysis. Analysis of the interview transcripts evidenced that clinicians and patients were supportive of a shared approach to treatment decision making in the context of a diagnosis of colorectal polyp cancer. Uncertainty, influences and information were among the themes identified to be preventing this happening at present. This study identified themes which were common to both groups. These were: complexity of the risk information; lack of patient information resources; system factors and time. This research study has evidenced several factors such as uncertainty, complexity of risk information and influences on decisions which are preventing patients being involved in treatment decisions following a diagnosis of colorectal polyp cancer. Recommendations for improvements in practice, including a framework to assist treatment decision making in the future have been highlighted. [Abstract copyright: This article is protected by copyright. All rights reserved.]
    • Defining trajectories of response in patients with psoriasis treated with biologic therapies

      Geifman, N.; orcid: 0000-0003-2956-6676; email: nophar.geifman@manchester.ac.uk; Azadbakht, N.; Zeng, J.; Wilkinson, T.; Dand, N.; Buchan, I.; Stocken, D.; Di Meglio, P.; orcid: 0000-0002-2066-7780; Warren, R.B.; Barker, J.N.; et al. (2021-06-04)
      Summary: Background: The effectiveness and cost‐effectiveness of biologic therapies for psoriasis are significantly compromised by variable treatment responses. Thus, more precise management of psoriasis is needed. Objectives: To identify subgroups of patients with psoriasis treated with biologic therapies, based on changes in their disease activity over time, that may better inform patient management. Methods: We applied latent class mixed modelling to identify trajectory‐based patient subgroups from longitudinal, routine clinical data on disease severity, as measured by the Psoriasis Area and Severity Index (PASI), from 3546 patients in the British Association of Dermatologists Biologics and Immunomodulators Register, as well as in an independent cohort of 2889 patients pooled across four clinical trials. Results: We discovered four discrete classes of global response trajectories, each characterized in terms of time to response, size of effect and relapse. Each class was associated with differing clinical characteristics, e.g. body mass index, baseline PASI and prevalence of different manifestations. The results were verified in a second cohort of clinical trial participants, where similar trajectories following the initiation of biologic therapy were identified. Further, we found differential associations of the genetic marker HLA‐C*06:02 between our registry‐identified trajectories. Conclusions: These subgroups, defined by change in disease over time, may be indicative of distinct endotypes driven by different biological mechanisms and may help inform the management of patients with psoriasis. Future work will aim to further delineate these mechanisms by extensively characterizing the subgroups with additional molecular and pharmacological data.
    • Definition of Biologically Distinct Groups of Conjunctival Melanomas According to Etiological Factors and Implications for Precision Medicine

      Gardrat, Sophie; email: sophie.gardrat@curie.fr; Houy, Alexandre; orcid: 0000-0001-6267-2353; email: alexandre.houy@curie.fr; Brooks, Kelly; email: Kelly.Brooks@qimrberghofer.edu.au; Cassoux, Nathalie; email: nathalie.cassoux@curie.fr; Barnhill, Raymond; email: raymond.barnhill@curie.fr; Dayot, Stéphane; email: stephane.dayot@curie.fr; Bièche, Ivan; email: ivan.bieche@curie.fr; Raynal, Virginie; email: virginie.raynal@curie.fr; Baulande, Sylvain; email: sylvain.baulande@curie.fr; Marais, Richard; email: Richard.Marais@cruk.manchester.ac.uk; et al. (MDPI, 2021-07-30)
      Conjunctival melanoma (ConjMel) is a potentially deadly ocular melanoma, originating from partially sunlight-exposed mucosa. We explored the mutational landscape of ConjMel and studied the correlation with etiological factors. We collected 47 primary ConjMel samples and performed next-generation sequencing of 400 genes. Hotspot mutations in BRAF, NRAS, HRAS, and KIT were observed in 16 (34%), 5 (11%), 2, and 2 cases, respectively. Patients with BRAF and CDKN2A-mutated ConjMel tended to be younger while the NF1-mutated one tended to be older. The eight tumors arising from nevi were enriched in CTNNB1 mutations (63% vs. 8%; Fisher’s exact p-test = 0.001) compared to non-nevi ConjMel and five were devoid of BRAF, RAS, NF1, or KIT mutations, suggesting a specific oncogenic process in these tumors. The two KIT-mutated cases carried SF3B1 mutations and were located on sun-protected mucosa, a genotype shared with genital and anorectal mucosal melanomas. Targetable mutations were observed in ERBB2, IDH1, MET, and MAP2K1 (one occurrence each). Mutational landscape of ConjMel characterizes distinct molecular subtypes with oncogenic drivers common with mucosal and skin melanomas. CTNNB1 mutations were associated with nevus-derived ConjMel. Concomitant KIT/SF3B1 mutations in sun-protected cases suggest a common tumorigenic process with genital and anorectal mucosal melanomas.
    • Deformation Enhanced Diffusion in Aluminium Alloys

      Robson, J. D.; email: joseph.robson@manchester.ac.uk (Springer US, 2020-08-18)
      Abstract: Deformation introduces defects such as dislocations and excess vacancies that can strongly influence diffusion rates in aluminium alloys. This is of great importance in understanding the effect of deformation on processes such as precipitation hardening, which can be accelerated by orders of magnitude by the defects introduced. In this work, a simple and widely used classical model has been employed to explore the effect of process variables on diffusion enhancement due to deformation-induced excess vacancies and dislocations. It is demonstrated that in aluminium alloys, the strain rates and temperatures used in processing and testing encompass a range of regimes. At low strain rate or high temperature, a steady state becomes established in which the deformation enhancement depends on strain rate but not strain. Conversely, at high strain rate or low temperature, deformation enhancement is insensitive to strain rate but increases with strain. For all conditions, the effect of excess vacancies is much stronger than the direct effect of pipe diffusion along dislocations. The predicted deformation-induced vacancy concentration can exceed that expected after rapid quenching by an order of magnitude, but the lifetime of the deformation-induced vacancies is much shorter. Finally, limitations of the classical model and suggestions for improvement are proposed.
    • Delivery preferences for psychological intervention in cardiac rehabilitation: a pilot discrete choice experiment.

      Shields, Gemma Elizabeth; orcid: 0000-0003-4869-7524; email: gemma.shields@manchester.ac.uk; Wright, Stuart; orcid: 0000-0002-4064-7998; Wells, Adrian; Doherty, Patrick; Capobianco, Lora; Davies, Linda Mary (2021-08-01)
      <h4>Background</h4>Cardiac rehabilitation (CR) is a programme of care offered to people who recently experienced a cardiac event. There is a growing focus on home-based formats of CR and a lack of evidence on preferences for psychological care in CR. This pilot study aimed to investigate preferences for delivery attributes of a psychological therapy intervention in CR patients with symptoms of anxiety and/or depression.<h4>Methods</h4>A discrete choice experiment (DCE) was conducted and recruited participants from a feasibility trial. Participants were asked to choose between two hypothetical interventions, described using five attributes; intervention type (home or centre-based), information provided, therapy manual format, cost to the National Health Service (NHS) and waiting time. A separate opt-out was included. A conditional logit using maximum likelihood estimation was used to analyse preferences. The NHS cost was used to estimate willingness to pay for aspects of the intervention delivery.<h4>Results</h4>35 responses were received (39% response rate). Results indicated that participants would prefer to receive any form of therapy compared with no therapy. Statistically significant results were limited, but included participants being keen to avoid not receiving information prior to therapy (β=-0.270; p=0.03) and preferring a lower cost to the NHS (β=-0.001; p=0.00). No significant results were identified for the type of psychological intervention, format of therapy/exercises and programme start time. Coefficients indicated preferences were stronger for home-based therapy compared with centre-based, but this was not significant.<h4>Conclusions</h4>The pilot study demonstrates the feasibility of a DCE in this group, it identifies potential attributes and levels, and estimates the sample sizes needed for a full study. Preliminary evidence indicated that sampled participants tended to prefer home-based psychological therapy in CR and wanted to receive information before initiating therapy. Results are limited due to the pilot design and further research is needed.
    • Delivery preferences for psychological intervention in cardiac rehabilitation: a pilot discrete choice experiment.

      Shields, Gemma Elizabeth; orcid: 0000-0003-4869-7524; email: gemma.shields@manchester.ac.uk; Wright, Stuart; Wells, Adrian; Doherty, Patrick; Capobianco, Lora; Davies, Linda Mary (2021-08)
      Cardiac rehabilitation (CR) is a programme of care offered to people who recently experienced a cardiac event. There is a growing focus on home-based formats of CR and a lack of evidence on preferences for psychological care in CR. This pilot study aimed to investigate preferences for delivery attributes of a psychological therapy intervention in CR patients with symptoms of anxiety and/or depression. A discrete choice experiment (DCE) was conducted and recruited participants from a feasibility trial. Participants were asked to choose between two hypothetical interventions, described using five attributes; intervention type (home or centre-based), information provided, therapy manual format, cost to the National Health Service (NHS) and waiting time. A separate opt-out was included. A conditional logit using maximum likelihood estimation was used to analyse preferences. The NHS cost was used to estimate willingness to pay for aspects of the intervention delivery. 35 responses were received (39% response rate). Results indicated that participants would prefer to receive any form of therapy compared with no therapy. Statistically significant results were limited, but included participants being keen to avoid not receiving information prior to therapy (β=-0.270; p=0.03) and preferring a lower cost to the NHS (β=-0.001; p=0.00). No significant results were identified for the type of psychological intervention, format of therapy/exercises and programme start time. Coefficients indicated preferences were stronger for home-based therapy compared with centre-based, but this was not significant. The pilot study demonstrates the feasibility of a DCE in this group, it identifies potential attributes and levels, and estimates the sample sizes needed for a full study. Preliminary evidence indicated that sampled participants tended to prefer home-based psychological therapy in CR and wanted to receive information before initiating therapy. Results are limited due to the pilot design and further research is needed. [Abstract copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.]
    • Dementia Early-Stage Cognitive Aids New Trial (DESCANT) of memory aids and guidance for people with dementia: randomised controlled trial.

      Clarkson, Paul; orcid: 0000-0002-0778-312X; email: paul.clarkson@manchester.ac.uk; Pitts, Rosa; Islam, Saiful; Peconi, Julie; Russell, Ian; orcid: 0000-0002-0069-479X; Fegan, Greg; orcid: 0000-0002-2663-2765; Beresford, Rebecca; Entwistle, Charlotte; Gillan, Vincent; Orrell, Martin; et al. (2021-10-19)
      Common memory aids for people with dementia at home are recommended. However, rigorous evaluation is lacking, particularly what guidance or support is valued. To investigate effects of memory aids and guidance by dementia support practitioners (DSPs) for people in early-stage dementia through a pragmatic, randomised controlled trial. Of 469 people with mild-to-moderate dementia and their informal carers, 468 were randomised to a DSP with memory aids or to usual care plus existing dementia guide. Allocation was stratified by Trust/Health Board; time since first attendance at memory service; gender; age; and living with primary carer or not. Primary outcome was Bristol Activities of Daily Living Scale (BADLS) Score at 3 and 6 months (primary end-point). Secondary outcomes for people with dementia: quality of life (CASP-19; DEMQOL); cognition and functioning (Clinical Dementia Rating Scale; S-MMSE); capability (ICECAP-O); social networks (LSNS-R); and instrumental daily living activities (R-IDDD). Secondary outcomes for carers: psychological health (GHQ-12); sense of competence (SSCQ). DSPs were successfully trained, compliance was good and welcomed by participants. Mean 6 months BADLS Score increased to 14.6 (SD: 10.4) in intervention and 12.6 (SD: 8.1) in comparator, indicative of greater dependence in the activities of daily living. Adjusted between-group difference was 0.38 (95% CI: -0.89 to 1.65, p=0.56). Though this suggests greater dependency in the intervention group the difference was not significant. No differences were found in secondary outcomes. This intervention did not maintain independence in the activities of daily living with no improvement in other outcomes for people with dementia or carers. Current Controlled Trials ISRCTN12591717. [Abstract copyright: © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.]
    • Deoxyribonucleic acid polymer nanoparticle hydrogels.

      Bagley, Robert H T; orcid: 0000-0001-9373-123X; Jones, Samuel T; orcid: 0000-0002-3907-0810 (2021-10-27)
      Polymer nanoparticle hydrogels made of deoxyribonucleic acid and silica have been prepared and shown to display shear thinning and self-healing properties, sustained release of cargo and enzymatic degradation.
    • Depression, anxiety, and loneliness among adolescents and young adults with IBD in the UK: the role of disease severity, age of onset, and embarrassment of the condition

      Qualter, Pamela; orcid: 0000-0001-6114-3820; email: pamela.qualter@manchester.ac.uk; Rouncefield-Swales, Alison; Bray, Lucy; Blake, Lucy; Allen, Steven; Probert, Chris; Crook, Kay; Carter, Bernie; orcid: 0000-0001-5226-9878; email: bernie.carter@edgehill.ac.uk (Springer International Publishing, 2020-09-30)
      Abstract: Purpose: Adolescents and young adults (AYA) with Inflammatory Bowel Disease (IBD) report higher depressive symptoms and anxiety compared to healthy controls, with disease severity and abdominal pain being important factors. In the current study, building on what young people had told us in our previous work, we examined whether embarrassment of the condition, social self-efficacy, and friendship quality mediated the relationship between abdominal pain and disease severity, and mental health/well-being. We also included loneliness as a component of well-being. Methods: Data on depression, anxiety, loneliness, friendship quality, social self-efficacy, and disease embarrassment were collected from 130 AYA with IBD ages 14–25 years; data on disease severity and abdominal pain were taken from their medical records. Structural Equation Modeling (SEM) was used to test the relationships between the variables. Results: Using SEM, we established that higher IBD disease activity negatively impacted how AYA felt about their friendships and how embarrassed they were about their condition; embarrassment then influenced reports of mental health, including loneliness. Abdominal pain, disease onset, and social self-efficacy directly predicted internalising problems. Conclusion: In this sample of 14–25-year-old patients with IBD, specifics about the disease (severity and pain) predicted poorer mental health, suggesting discussion of mental health should be part of the clinical dialogue between patient and consultant. In addition, embarrassment about their condition increased depression, anxiety, and loneliness, mediating the relationship between disease severity and well-being. Thus, it is important to consider how perceived stigma affects those with chronic illness, and those issues should be explored in clinic.
    • Descriptions and the materiality of texts

      guest-editor: Vitellone, Nicole; guest-editor: Mair, Michael; guest-editor: Kierans, Ciara; Mazza, Roberta; orcid: 0000-0001-6508-8259; email: roberta.mazza@manchester.ac.uk (SAGE Publications, 2021-03-02)
      This article builds on the notions of thick and thin description elaborated by Geertz and looks at what descriptive methods have been used in the field of papyrology, a sub-discipline of classics that studies ancient manuscripts on papyrus fragments recovered through legal and illegal excavations in Egypt from the 19th century. Past generations of papyrologists have described papyri merely as resources to retrieve ancient ‘texts’. In the article I argue these descriptions have had negative effects in the way this ancient material has been studied, preserved, and also exchanged through the antiquities market. Through a series of case studies, I offer an alternative description of papyrus fragments as things, which have a power that can be activated under specific circumstances or entanglements. In demonstrating papyrus manuscripts’ unstable nature and shifting meanings, which are contingent on such entanglements, the article calls for a new politics and ethics concerning their preservation and exchange.