• ‘Radial force’ of colonic stents: A parameter without consistency, definition or standard

      Laasch, Hans-Ulrich; orcid: 0000-0003-3109-6933; Milward, Graham D.; orcid: 0000-0002-0980-6567; Edwards, Derek W.; orcid: 0000-0001-6192-5056 (Society of Gastrointestinal Intervention, 2020-07-31)
    • Radical hydroxymethylation of alkyl iodides using formaldehyde as a C1 synthon.

      Caiger, Lewis; orcid: 0000-0001-5156-9684; Sinton, Conar; orcid: 0000-0002-5588-7548; Constantin, Timothée; orcid: 0000-0001-5376-1557; Douglas, James J; Sheikh, Nadeem S; Juliá, Fabio; orcid: 0000-0001-8903-4482; Leonori, Daniele; orcid: 0000-0002-7692-4504 (2021-07-06)
      Radical hydroxymethylation using formaldehyde as a C1 synthon is challenging due to the reversible and endothermic nature of the addition process. Here we report a strategy that couples alkyl iodide building blocks with formaldehyde through the use of photocatalysis and a phosphine additive. Halogen-atom transfer (XAT) from α-aminoalkyl radicals is leveraged to convert the iodide into the corresponding open-shell species, while its following addition to formaldehyde is rendered irreversible by trapping the transient O-radical with PPh . This event delivers a phosphoranyl radical that re-generates the alkyl radical and provides the hydroxymethylated product. [Abstract copyright: This journal is © The Royal Society of Chemistry.]
    • Radical hydroxymethylation of alkyl iodides using formaldehyde as a C1 synthon.

      Caiger, Lewis; orcid: 0000-0001-5156-9684; Sinton, Conar; orcid: 0000-0002-5588-7548; Constantin, Timothée; orcid: 0000-0001-5376-1557; Douglas, James J; Sheikh, Nadeem S; Juliá, Fabio; orcid: 0000-0001-8903-4482; Leonori, Daniele; orcid: 0000-0002-7692-4504 (2021-07-06)
      Radical hydroxymethylation using formaldehyde as a C1 synthon is challenging due to the reversible and endothermic nature of the addition process. Here we report a strategy that couples alkyl iodide building blocks with formaldehyde through the use of photocatalysis and a phosphine additive. Halogen-atom transfer (XAT) from α-aminoalkyl radicals is leveraged to convert the iodide into the corresponding open-shell species, while its following addition to formaldehyde is rendered irreversible by trapping the transient O-radical with PPh<sub>3</sub>. This event delivers a phosphoranyl radical that re-generates the alkyl radical and provides the hydroxymethylated product.
    • Raising the bar? The impact of the UNISON ethical care campaign in UK domiciliary care

      Johnson, Mathew; email: Mathew.johnson@manchester.ac.uk; Rubery, Jill; Egan, Matthew (SAGE Publications, 2021-07-15)
      This article critically analyses a major trade union initiative in the United Kingdom to raise standards in public contracts for domiciliary care, and in turn to improve wages and working conditions for outsourced care workers. The campaign successfully built alliances with national employer representatives, and around 25 per cent of commissioning bodies in England, Scotland and Wales have signed a voluntary charter that guarantees workers an hourly living wage, payment for travel time and regular working hours. The campaign overall, however, has had only limited effects on standards across the sector, in which low wages, zero-hours contracts and weak career paths predominate. Furthermore, the campaign has not yet yielded significant gains in terms of union recruitment, although there are signs of sporadic mobilisations of care workers in response to localised disputes.
    • Rare GATA6 variants associated with risk of congenital heart disease phenotypes in 200,000 UK Biobank exomes.

      Williams, Simon G; Byrne, Dominic J F; Keavney, Bernard D; orcid: 0000-0001-9573-0812; email: bernard.keavney@manchester.ac.uk (2021-09-07)
      Congenital heart disease (CHD) has a complex and largely uncharacterised genetic etiology. Using 200,000 UK Biobank (UKB) exomes, we assess the burden of ultra-rare, potentially pathogenic variants in the largest case/control cohort of predominantly mild CHD to date. We find an association with GATA6, a member of the GATA family of transcription factors that play an important role during heart development and has been linked with several CHD phenotypes previously. Several identified GATA6 variants are previously unreported and their roles in conferring risk to CHD warrants further study. We demonstrate that despite limitations regarding detailed familial phenotype information in large-scale biobank projects, through careful consideration of case and control cohorts it is possible to derive important associations. [Abstract copyright: © 2021. The Author(s).]
    • Ratings of perceived exertion at the ventilatory anaerobic threshold in people with coronary heart disease: A CARE CR study.

      Nichols, Simon; email: s.j.nichols@shu.ac.uk; Engin, Buket; Carroll, Sean; Buckley, John P.; Ingle, Lee (2020-12-04)
      Exercise prescription guidelines for individuals undergoing cardiovascular rehabilitation (CR) are based on heart rate training zones and rating of perceived exertion (RPE). United Kingdom guidelines indicate that patients should exercise at an intensity of RPE 11 to 14. We aimed to determine the accuracy of this approach by comparing this RPE range with an objectively measured marker of exercise intensity, the ventilatory anaerobic threshold (VAT), and examine whether baseline directly determined cardiorespiratory fitness (CRF) affects the association between VAT and RPE. Participants underwent a maximal cardiopulmonary exercise test before an 8-week community-based CR programme. Peak oxygen uptake (V̇O2peak) and VAT were recorded, and RPE at the workload at which VAT was identified was recorded. Data were then split into tertiles, based on V̇O2peak, to determine whether RPE at the VAT differed in participants with low, moderate or higher CRF. We included 70 individuals [mean (SD) age 63.1 (10.0) years; body mass index 29.4 (4.0) kg/m2; 86% male]. At baseline, the mean RPE at the VAT (RPE@VAT) was 11.8 (95% confidence interval 11-12.6) and significantly differed between low and high CRF groups (P<0.001). The mean RPE@VAT was 10.1 (8.7-11.5), 11.8 (10.5-13.0), and 13.7 (12.5-14.9) for low, moderate and high CRF groups, respectively. When using RPE to guide exercise intensity in CR populations, one must consider the effect of baseline CRF. Mean RPEs of ∼10, 12 and 14 correspond to the VAT in low, moderate and higher-fit patients, respectively. [Abstract copyright: Copyright © 2020 Elsevier Masson SAS. All rights reserved.]
    • Reading Hilary Mantel: Haunted Decades

      Pollard, Eileen (Oxford University Press (OUP), 2021-07-10)
    • Reading Hilary Mantel: Haunted Decades

      Pollard, Eileen (Oxford University Press (OUP), 2021-07-10)
    • Real-time monitoring of crystallization from solution by using an interdigitated array electrode sensor.

      Tong, Jincheng; orcid: 0000-0001-7762-1460; Doumbia, Amadou; orcid: 0000-0002-4136-9029; Turner, Michael L; orcid: 0000-0003-2853-5632; Casiraghi, Cinzia; orcid: 0000-0001-7185-0377 (2021-04-27)
      Monitoring crystallization events in real-time is challenging but crucial for understanding the molecular dynamics associated with nucleation and crystal growth, some of nature's most ubiquitous phenomena. Recent observations have suggested that the traditional nucleation model, which describes the nucleus having already the final crystal structure, may not be valid. It appears that the molecular assembly can range during nucleation from crystalline to partially ordered to totally amorphous phases, and can change its structure during the crystallization process. Therefore, it is of critical importance to develop methods that are able to provide real-time monitoring of the molecular interactions with high temporal resolution. Here, we demonstrate that a simple and scalable approach based on interdigitated electrode array sensors (IESs) is able to provide insights on the dynamics of the crystallization process with a temporal resolution of 15 ms.
    • Reasons for indoor tanning use and the acceptability of alternatives: A qualitative study.

      Lyons, Stephanie; Lorigan, Paul; Green, Adele C; Ferguson, Ashley; Epton, Tracy; email: tracy.epton@manchester.ac.uk (2021-08-20)
      Using indoor tanning devices is associated with substantial health consequences, such as an increased risk of melanoma and other skin cancers. Many people including minors and some at high risk of skin cancer continue to use these devices. In the absence of effective restrictions on use, it is important that behaviour change interventions are designed to reduce indoor tanning. To explore reasons for use of indoor tanning devices and the acceptability of alternatives in adult users residing in North-West England. Participants were required to be current indoor tanners aged 18 years and above and were recruited online. Twenty-one participants took part in either a focus group or semi-structured interview. An inductive thematic analysis was conducted. Six themes were identified: psychological benefits; improving physical health; denial of health risks; alternatives do not meet psychological needs; alternatives do not meet physical needs; and perceived side-effects. Participants used indoor tanning devices to improve their self-esteem and to prevent sun damage to their skin (by gaining a 'base tan'). Participants appeared to justify their usage by responding defensively to avoid accepting they were at risk, exaggerating the benefits of indoor tanning, and discounting alternatives to indoor tanning. Alternatives to indoor tanning were perceived as risky for health, inadequate to provide the desired aesthetic, and incapable of meeting their self-esteem needs. Interventions to reduce indoor tanning behaviour should increase sources of self-esteem other than appearance, increase media literacy and address defensive responses to information around indoor tanning and alternatives. Further research is needed to develop these interventions and assess their feasibility. [Abstract copyright: Copyright © 2021. Published by Elsevier Ltd.]
    • Reasons for success and lessons learnt from nanoscale vaccines against COVID-19.

      Kisby, Thomas; orcid: 0000-0002-8432-7910; Yilmazer, Açelya; orcid: 0000-0003-2712-7450; Kostarelos, Kostas; orcid: 0000-0002-2224-6672; email: kostas.kostarelos@manchester.ac.uk (2021-08)
    • Recommendations for Transdisciplinary Professional Competencies and Ethics for Animal-Assisted Therapies and Interventions.

      Trevathan-Minnis, Melissa; Johnson, Amy; orcid: 0000-0003-3536-9193; Howie, Ann R (2021-12-02)
      AAI is a transdisciplinary field that has grown exponentially in recent decades. This growth has not always been synergistic across fields, creating a need for more consistent language and standards, a call for which many professionals in the field have made. Under the umbrella of human-animal interactions (HAI) is animal-assisted interventions (AAIs), which have a more goal-directed intention with animals who have been assessed for therapeutic, educational, or vocational work. The current article offers a brief history and efficacy of HAI, describes the limitations and gaps within the field and recommends a new set of competencies and guidelines that seek to create some of the needed common language and standards for AAI work to address these limitations.
    • Recomposing persons: Scavenging and storytelling in a birth cohort archive

      Tinkler, Penny; orcid: 0000-0002-9918-9821; email: penny.tinkler@manchester.ac.uk; Cruz, Resto; orcid: 0000-0003-2621-6232; Fenton, Laura (SAGE Publications, 2021-03-08)
      Birth cohort studies can be used not only to generate population-level quantitative data, but also to recompose persons. The crux is how we understand data and persons. Recomposition entails scavenging for various (including unrecognised) data. It foregrounds the perspective and subjectivity of survey participants, but without forgetting the partiality and incompleteness of the accounts that it may generate. Although interested in the singularity of individuals, it attends to the historical and relational embeddedness of personhood. It examines the multiple and complex temporalities that suffuse people’s lives, hence departing from linear notions of the life course. It implies involvement, as well as reflexivity, on the part of researchers. It embraces the heterogeneity and transformations over time of scientific archives and the interpretive possibilities, as well as incompleteness, of birth cohort studies data. Interested in the unfolding of lives over time, it also shines light on meaningful biographical moments.
    • Reduced physiologically-based pharmacokinetic model of dabigatran etexilate-dabigatran and its application for prediction of intestinal P-gp-mediated drug-drug interactions.

      Lang, Jennifer; Vincent, Ludwig; Chenel, Marylore; Ogungbenro, Kayode; Galetin, Aleksandra; email: aleksandra.galetin@manchester.ac.uk (2021-07-11)
      Dabigatran etexilate (DABE) has been suggested as a clinical probe for intestinal P-glycoprotein (P-gp)-mediated drug-drug interaction (DDI) studies and, as an alternative to digoxin. Clinical DDI data with various P-gp inhibitors demonstrated a dose-dependent inhibition of P-gp with DABE. The aims of this study were to develop a joint DABE (prodrug)-dabigatran reduced physiologically-based-pharmacokinetic (PBPK) model and to evaluate its ability to predict differences in P-gp DDI magnitude between a microdose and a therapeutic dose of DABE. A joint DABE-dabigatran PBPK model was developed with a mechanistic intestinal model accounting for the regional P-gp distribution in the gastrointestinal tract. Model input parameters were estimated using DABE and dabigatran pharmacokinetic (PK) clinical data obtained after administration of DABE alone or with a strong P-gp inhibitor, itraconazole, and over a wide range of DABE doses (from 375 µg to 400 mg). Subsequently, the model was used to predict extent of DDI with additional P-gp inhibitors and with different DABE doses. The reduced DABE-dabigatran PBPK model successfully described plasma concentrations of both prodrug and metabolite following administration of DABE at different dose levels and when co-administered with itraconazole. The model was able to capture the dose dependency in P-gp mediated DDI. Predicted magnitude of itraconazole P-gp DDI was higher at the microdose (predicted vs. observed median fold-increase in AUC /AUC (min-max) = 5.88 (4.29-7.93) vs. 6.92 (4.96-9.66) ng.h/mL) compared to the therapeutic dose (predicted median fold-increase in AUC /AUC  = 3.48 (2.37-4.84) ng.h/mL). In addition, the reduced DABE-dabigatran PBPK model predicted successfully the extent of DDI with verapamil and clarithromycin as P-gp inhibitors. Model-based simulations of dose staggering predicted the maximum inhibition of P-gp when DABE microdose was concomitantly administered with itraconazole solution; simulations also highlighted dosing intervals required to minimise the DDI risk depending on the DABE dose administered (microdose vs. therapeutic). This study provides a modelling framework for the evaluation of P-gp inhibitory potential of new molecular entities using DABE as a clinical probe. Simulations of dose staggering and regional differences in the extent of intestinal P-gp inhibition for DABE microdose and therapeutic dose provide model-based guidance for design of prospective clinical P-gp DDI studies. [Abstract copyright: Copyright © 2021. Published by Elsevier B.V.]
    • Reducing bias in trials due to reactions to measurement: experts produced recommendations informed by evidence.

      French, David P; email: david.french@manchester.ac.uk; Miles, Lisa M; Elbourne, Diana; Farmer, Andrew; Gulliford, Martin; Locock, Louise; Sutton, Stephen; McCambridge, Jim; MERIT Collaborative group (2021-07-03)
      This study (MEasurement Reactions In Trials) aimed to produce recommendations on how best to minimise bias from measurement reactivity in randomised controlled trials of interventions to improve health. The MERIT study consisted of: (a) an updated systematic review that examined whether measuring participants had effects on participants' health-related behaviours, relative to no-measurement controls, and three rapid reviews to identify: (i) existing guidance on measurement reactivity; (ii) existing systematic reviews of studies that have quantified the effects of measurement on behavioural or affective outcomes; and (iii) studies that have investigated the effects of objective measurements of behaviour on health-related behaviour; (b) an Delphi study to identify the scope of the recommendations; and (c) an expert workshop in October 2018 to discuss potential recommendations in groups. Fourteen recommendations were produced by the expert group to: (a) identify whether bias is likely to be a problem for a trial; (b) decide whether to collect data about whether bias is likely to be a problem; (c) design trials to minimise the likelihood of this bias. These recommendations raise awareness of how and where taking measurements can produce bias in trials, and are thus helpful for trial design. [Abstract copyright: Copyright © 2021. Published by Elsevier Inc.]
    • Reframing how we care for people with persistent non-traumatic musculoskeletal pain. Suggestions for the rehabilitation community

      Lewis, Jeremy S.; orcid: 0000-0001-7870-9165; Stokes, Emma K.; Gojanovic, Boris; orcid: 0000-0001-5075-9371; Gellatly, Pamela; orcid: 0000-0001-7401-2096; Mbada, Chidozie; orcid: 0000-0003-3666-7432; Sharma, Saurab; orcid: 0000-0002-9817-5372; Diener, Ina; orcid: 0000-0001-7426-4840; O’Sullivan, Peter (Elsevier, 2021-06-05)
      There have been repeated calls to re-evaluate how clinicians provide care for people presenting with persistent non-traumatic musculoskeletal conditions. One suggestion is to move away from the ‘we can fix and cure you’ model to adopting an approach that is more consistent with approaches used when managing other persistent non-communicable diseases; education, advice, a major focus on self-management including lifestyle behavioural change, physical activity and medications as required. Currently the global delivery of musculoskeletal care has many of the elements of a ‘super wicked problem’, namely conflict of interest from stake-holders due to the consequences of change, prevailing expectation of a structural diagnosis and concomitant fix for musculoskeletal pain, persistent funding of high risk, more expensive care when low risk more economic viable options that don’t impact on the quality of outcome exist, and an unquestionable need to find a solution now with the failure resulting in a growing social and economic burden for future generations. To address these issues, 100 participants included clinicians, educators and researchers from low-, middle- and high-income countries, eight presenters representing the physiotherapy, sport medicine and the orthopaedic professions and the insurance industry, together with three people who shared their lived experiences of persistent musculoskeletal pain, discussed the benefits and barriers of implementing change to address this problem. This paper presents the results from the stakeholders’ contextual analysis and forms the basis for the proposed next steps from an action and advocacy perspective.
    • Reframing how we care for people with persistent non-traumatic musculoskeletal pain. Suggestions for the rehabilitation community

      Lewis, Jeremy S.; orcid: 0000-0001-7870-9165; Stokes, Emma K.; Gojanovic, Boris; orcid: 0000-0001-5075-9371; Gellatly, Pamela; orcid: 0000-0001-7401-2096; Mbada, Chidozie; orcid: 0000-0003-3666-7432; Sharma, Saurab; orcid: 0000-0002-9817-5372; Diener, Ina; orcid: 0000-0001-7426-4840; O’Sullivan, Peter
      There have been repeated calls to re-evaluate how clinicians provide care for people presenting with persistent non-traumatic musculoskeletal conditions. One suggestion is to move away from the ‘we can fix and cure you’ model to adopting an approach that is more consistent with approaches used when managing other persistent non-communicable diseases; education, advice, a major focus on self-management including lifestyle behavioural change, physical activity and medications as required. Currently the global delivery of musculoskeletal care has many of the elements of a ‘super wicked problem’, namely conflict of interest from stake-holders due to the consequences of change, prevailing expectation of a structural diagnosis and concomitant fix for musculoskeletal pain, persistent funding of high risk, more expensive care when low risk more economic viable options that don’t impact on the quality of outcome exist, and an unquestionable need to find a solution now with the failure resulting in a growing social and economic burden for future generations. To address these issues, 100 participants included clinicians, educators and researchers from low-, middle- and high-income countries, 8 presenters representing the physiotherapy, sport medicine and the orthopaedic professions and the insurance industry, together with 3 people who shared their lived experiences of persistent musculoskeletal pain, discussed the benefits and barriers of implementing change to address this problem. This paper presents the results from the stakeholders’ contextual analysis and forms the basis for the proposed next steps from an action and advocacy perspective.