• Adolescents’ experiences of fluctuating pain in musculoskeletal disorders: a qualitative systematic review and thematic synthesis

      Khanom, Sonia; orcid: 0000-0002-9869-2476; email: sonia.khanom@postgrad.manchester.ac.uk; McDonagh, Janet E.; Briggs, Michelle; Bakir, Ebru; McBeth, John (BioMed Central, 2020-10-02)
      Abstract: Background: Adolescents with chronic musculoskeletal pain experience daily fluctuations in pain. Although not all fluctuations are bothersome, pain flares are a distinct type of symptom fluctuation with greater impact. Since literature on the experience of pain flares is non-existent, the aim of this review was to (i) synthesise the qualitative literature on adolescents’ experiences of fluctuating pain in musculoskeletal disorders in order to (ii) identify knowledge gaps to inform future research on pain flares. Methods: Electronic databases (CINAHL, MEDLINE, EMBASE, PsycINFO), grey literature and reference lists were searched from inception to June 2018 for qualitative studies reporting adolescents’ experiences of pain. Comprehensiveness of reporting was assessed using the Consolidated Criteria for Reporting Qualitative Health Research. Studies were analysed using thematic synthesis. Results: Of the 3787 records identified, 32 studies (n = 536) were included. Principal findings were synthesised under three key themes: 1) symptom experience, 2) disruption and loss, and 3) regaining control. The first theme (symptom experience) describes adolescent’s perception and interpretation of pain fluctuations. The second theme (disruption and loss) describes the physical, social and emotional constraints faced as a result of changes in pain. The third theme (regaining control) describes coping strategies used to resist and accommodate unpredictable phases of pain. Each theme was experienced differently depending on adolescents’ characteristics such as their developmental status, pain condition, and the duration of the pain experience. Conclusions: Adolescents with chronic musculoskeletal pain live with a daily background level of symptoms which frequently fluctuate and are associated with functional and emotional difficulties. It was not clear whether these symptoms and challenges were experienced as part of ‘typical’ fluctuations in pain, or whether they reflect symptom exacerbations classified as ‘flares’. Further research is needed to explore the frequency and characteristics of pain flares, and how they differ from their typical fluctuations in pain. The review also highlights areas relating to the pain experience, symptom management and health service provision that require further exploration to support more personalised, tailored care for adolescents with chronic musculoskeletal pain.
    • Adult lifetime cost of hemophilia B management in the US: payer and societal perspectives from a decision analytic model

      Li, Nanxin; Sawyer, Eileen K.; Maruszczyk, Konrad; orcid: 0000-0002-0173-5020; Guzauskas, Greg; orcid: 0000-0002-9095-1672; Slomka, Marta T.; Burke, Tom; Martin, Antony P.; orcid: 0000-0003-4383-6038; O’Hara, Jamie; orcid: 0000-0001-8262-034X; Stevenson, Matt; orcid: 0000-0002-3099-9877; Recht, Michael; orcid: 0000-0002-2805-1016 (Informa UK Limited, 2021-03-02)
    • Adult lifetime cost of hemophilia B management in the US: Payer and societal perspectives from a decision analytic model

      Li, Nanxin; Sawyer, Eileen K.; Maruszczyk, Konrad; orcid: 0000-0002-0173-5020; Guzauskas, Greg; orcid: 0000-0002-9095-1672; Slomka, Marta T.; Burke, Tom; Martin, Antony P.; O’Hara, Jamie; Stevenson, Matt; Recht, Michael (Informa UK Limited, 2021-02-16)
    • Adult lifetime cost of hemophilia B management in the US: payer and societal perspectives from a decision analytic model

      Li, Nanxin; Sawyer, Eileen K.; Maruszczyk, Konrad; orcid: 0000-0002-0173-5020; Guzauskas, Greg; orcid: 0000-0002-9095-1672; Slomka, Marta T.; Burke, Tom; Martin, Antony P.; orcid: 0000-0003-4383-6038; O’Hara, Jamie; orcid: 0000-0001-8262-034X; Stevenson, Matt; orcid: 0000-0002-3099-9877; Recht, Michael; orcid: 0000-0002-2805-1016 (Informa UK Limited, 2021-03-02)
    • Adult lifetime cost of hemophilia B management in the US: Payer and societal perspectives from a decision analytic model.

      Li, Nanxin; Sawyer, Eileen K; Maruszczyk, Konrad; orcid: 0000-0002-0173-5020; Guzauskas, Greg; orcid: 0000-0002-9095-1672; Slomka, Marta T; Burke, Tom; Martin, Antony P; O'Hara, Jamie; Stevenson, Matt; Recht, Michael (2021-02-16)
      Hemophilia B (HB) is a rare congenital disorder characterized by bleeding-related complications which are managed by prophylactic or post-bleeding event ("on-demand") replacement of clotting factor IX (FIX). The standard of care for severe HB is life-long prophylaxis with standard half-life (SHL) or extended half-life (EHL) products given every 2-3 or 7-14 days, respectively. FIX treatment costs in the US have been investigated, but the lifetime costs of HB treatment have not been well characterized, particularly related to the impact of joint health deterioration and associated health resource utilization. We developed a decision-analytic model to explore outcomes, costs and underlying cost drivers associated with FIX treatment options over the lifetime of an adult with severe or moderately severe HB. With participation from clinicians, health technology assessment specialists and patient advocates, a Markov model was constructed to estimate bleeding events and costs associated with health states including 'bleed into joint', 'bleed not into joint', 'no bleed' and death. Sub-models of joint health were based on 0, 1, or ≥2 areas of chronic joint damage. US third-party payer and societal perspectives were considered with a lifetime horizon; sensitivity analyses tested the robustness of primary findings. Total adult lifetime costs per patient with severe and moderately severe HB were $21,086,607 for SHL FIX prophylaxis, $22,987,483 for EHL FIX prophylaxis, and $20,971,826 for on-demand FIX treatment. For FIX prophylaxis, the cost of FIX treatment account for >90% of the total HB treatment costs. This decision analytic model demonstrated significant economic burden associated with the current HB treatment paradigm.
    • Advances in Biofabrication for Tissue Engineering and Regenerative Medicine Applications

      Domingos, Marco; email: marco.domingos@manchester.ac.uk; Moxon, Sam; email: samuel.moxon@manchester.ac.uk (MDPI, 2021-05-09)
      Biofabrication strategies continue to gain considerable interest in the efforts to develop methods for better replicating in vitro models of human tissues [...]
    • Advances in Microstructural Understanding of Wrought Aluminum Alloys

      Robson, J. D.; email: joseph.d.robson@manchester.ac.uk; Engler, O.; Sigli, C.; Deschamps, A.; Poole, W. J. (Springer US, 2020-07-08)
      Abstract: Wrought aluminum alloys are an attractive option in the quest for lightweight, recyclable, structural materials. Modern wrought aluminum alloys depend on control of complex microstructures to obtain their properties. This requires an understanding of the coupling between alloy composition, processing, and microstructure. This paper summarizes recent work to understand microstructural evolution in such alloys, utilizing the advanced characterization techniques now available such as atom probe tomography, high-resolution electron microscopy, and synchrotron X-ray diffraction and scattering. New insights into precipitation processes, deformation behavior, and texture evolution are discussed. Recent progress in predicting microstructural evolution using computer modeling is also summarized.
    • Advancing Mental heaLth Provision In PHarmacY (AMPLIPHY): A feasibility study.

      Gorton, Hayley C; email: h.c.gorton@hud.ac.uk; Riste, Lisa; email: lisa.riste@manchester.ac.uk; Littlewood, Donna; email: donna.littlewood@manchester.ac.uk; Pickering, Gary; email: gary@cpcw.org.uk; Armitage, Christopher J; email: chris.armitage@manchester.ac.uk; Ashcroft, Darren M; email: darren.ashcroft@manchester.ac.uk (2021-11-09)
      Specifically-designed community pharmacy-based services represent opportunities to support people with their mental health. As few such services exist worldwide, the Advancing Mental HeaLth Provision In PharmacY (AMPLIPHY) was designed with stakeholders. The purpose was to support people with their mental health when initiated on new prescription or change in drug, dose or quantity of antidepressant, through a series of consultations (up to 3 months). The aim was to evaluate the feasibility of the AMPLIPHY service. The objectives were to: i) pilot the service; ii) examine anonymous consultation data to understand patients' characteristics, priorities and consultation focus and iii) Evaluate pharmacists' experiences. This service evaluation involved a concurrent mixed methods design. Patient characteristics were extracted from consultation notes and descriptive statistics applied. Content analysis was used to summarise consultation foci and comparisons between patients' priorities with consultation content were made. Pharmacists were interviewed at the start (n = 10) and end (n = 4) of the pilot with themes identified using thematic analysis. Seventy-six patients participated (63% of recruitment target). The median age was 39 (IQR 28-47) and 62% were female. Seventy percent of patients had one consultation, 26% had two and 4% had three. Prescription for new antidepressant was the most common reason for entry (74%) and sertraline was most prescribed (46%). Consultations commonly focussed on life experience (n = 51), medication (n = 47), health (n = 42), support (n = 36) and patients' expression of their feelings (n = 31). The pharmacists' experiences were summarised in three themes: i) Motivation, ii) Practicalities and iii) Experience and Outcomes. Pharmacists were motivated to deliver this novel service and some patients were willing to join the service. Analysis of patient demographics, consultation notes and interviews provide insight into the strengths and challenges of the service and provides a blueprint for future service developments. [Abstract copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.]
    • Affect in EMI at a German university

      Hunter, Michelle; Lanvers, Ursula (Amsterdam University Press, 2021-10-19)
      Englishization in German education is progressing rapidly, driven both by top-down and bottom-up forces (Lanvers & Hultgren, 2018). HE institutions are under pressure to be internationally attractive to fee-paying foreign students, but also need to offer high quality HE for home students. In the rapid move towards ‘Englishizing’ German HE institutions (Earls, 2014), little attention has been given to how stakeholders themselves – as participants but not enactors of this change – experience Englishization (Göpferich et al., 2019). This chapter explores how stakeholders experience affective dimensions of Englishization in a German HE institute. These insights can inform future training needs for English-medium instruction (EMI) staff and students. We conclude by linking our affective focus to wider development of Englishization in Germany.
    • Africanfuturist Socio‐Climatic Imaginaries and Nnedi Okorafor’s Wild Necropolitics

      Death, Carl; orcid: 0000-0002-1601-9473; email: carl.death@manchester.ac.uk (2021-07-21)
      Abstract: Dominant and insurgent socio‐climatic imaginaries struggle for influence over how the future is envisioned. Africanfuturist imaginaries have huge potential to unsettle racialised and gendered climate narratives. In this article I use Nnedi Okorafor’s novel Who Fears Death in order to challenge mainstream climate imaginaries and to imagine new forms of being and becoming in the context of climate change. Drawing on Achille Mbembe’s concepts of biopolitics and necropolitics, as well as black feminist traditions of imagining new genres of the human, I argue that Okorafor’s “wild necropolitics” illuminates how the forces of “wild nature” have become central features of the deployment of the means of destroying life, especially in the context of climate change. By examining the motifs of change, violence, wilderness and narration, I argue that reading and writing different stories about alternative climate futures is essential to the process of finding new ways of being and becoming human.
    • Age of people with type 2 diabetes and the risk of dying following SARS‐CoV‐2 infection

      Tian, Zixing; Heald, Adrian H.; orcid: 0000-0002-9537-4050; email: adrian.heald@manchester.ac.uk; Stedman, Mike; Fachim, Helene; Livingston, Mark; orcid: 0000-0001-6878-0769; Gibson, Martin; Peng, Yonghong; Ollier, William (2021-07-21)
    • Agents and Robots for Reliable Engineered Autonomy:A Perspective from the Organisers of AREA 2020

      Cardoso, Rafael C.; orcid: 0000-0001-6666-6954; email: rafael.cardoso@manchester.ac.uk; Ferrando, Angelo; orcid: 0000-0002-8711-4670; email: angelo.ferrando@dibris.unige.it; Briola, Daniela; orcid: 0000-0003-1994-8929; email: daniela.briola@unimib.it; Menghi, Claudio; orcid: 0000-0001-5303-8481; email: claudio.menghi@uni.lu; Ahlbrecht, Tobias; orcid: 0000-0002-4652-901X; email: tobias.ahlbrecht@tu-clausthal.de (MDPI, 2021-05-14)
      Multi-agent systems, robotics and software engineering are large and active research areas with many applications in academia and industry. The First Workshop on Agents and Robots for reliable Engineered Autonomy (AREA), organised the first time in 2020, aims at encouraging cross-disciplinary collaborations and exchange of ideas among researchers working in these research areas. This paper presents a perspective of the organisers that aims at highlighting the latest research trends, future directions, challenges, and open problems. It also includes feedback from the discussions held during the AREA workshop. The goal of this perspective is to provide a high-level view of current research trends for researchers that aim at working in the intersection of these research areas.
    • Aging well with psychosis.

      Smart, Emily L; email: emily.smart2@nhs.net; Berry, Katherine; email: katherine.berry@manchester.ac.uk; Palmier-Claus, Jasper; email: j.palmier-claus@lancaster.ac.uk; Brown, Laura J E; email: laura.brown@manchester.ac.uk (2021-03-31)
      Despite the unique challenges faced by people living with a severe mental illness, little work has been done to understand how these populations can age well. This study therefore aimed to explore the views of mid to older aged adults living with a psychosis on what it means to age well, and how they might be supported in this endeavor. Semi-structured interviews were conducted with sixteen individuals (age 50-74 years) diagnosed with psychosis-related disorders (e.g. schizophrenia). Inductive thematic analysis was used to analyze the data. Four themes were identified: (i) Engagement with Life - referring to participating in, and maintaining, activities that bring satisfaction and value; (ii) Attitude to Life and Aging - referring to a positive attitude and outlook, and accepting aging-related challenges; (iii) Health and Wellbeing - relating to keeping as physically and mentally fit as possible and (iv) Social Connections - referring to both personal and professional relationships, and feeling heard and understood by others. Whilst there were clear parallels between these results and those reported from other populations, participants aging with a psychosis revealed challenges, perceptions, and nuances that were unique to their situation. The importance of relationships with professionals, developing a mastery over their mental health difficulties, and the continued impact of stigma on aging well were highlighted. This suggests that approaches that target external societal factors, as well as therapeutic interventions focused on the individual, may help this population to age well. [Abstract copyright: Copyright © 2021 Elsevier Inc. All rights reserved.]
    • Aiming for Universal Health Coverage through insurance in Ethiopia: State infrastructural power and the challenge of enrolment.

      Lavers, Tom; email: tom.lavers@manchester.ac.uk (2021-06-21)
      Many developing countries are considering insurance as a means of pursuing Universal Health Coverage. A key challenge to confront is how to achieve high levels of health insurance enrolment. For voluntary schemes this entails mass awareness raising and promotional activity, though as schemes move to compulsory enrolment, monitoring and enforcement are required. This paper focuses on Ethiopia, which has made state health insurance for the informal sector a central pillar of its Universal Health Coverage strategy. The paper shows that high enrolment requires particular forms of state capacity, captured by Michael Mann's concept of state 'infrastructural power'. The paper draws on detailed case studies of insurance implementation in the Tigray and Oromiya regions of Ethiopia to illustrate variation in state infrastructural power and the implications for health insurance. Findings suggest that the potential of state health insurance as a means of promoting health access for a broad section of the population may be limited to the minority of countries or regions within countries exhibiting high levels of infrastructural power. [Abstract copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.]
    • Airway Bacteria Quantification Using Polymerase Chain Reaction Combined with Neutrophil and Eosinophil Counts Identifies Distinct COPD Endotypes

      Beech, Augusta; orcid: 0000-0002-2690-5364; email: augusta.beech@manchester.ac.uk; Lea, Simon; orcid: 0000-0003-3700-1886; email: Simon.lea@manchester.ac.uk; Li, Jian; email: Jian.Li@manchester.ac.uk; Jackson, Natalie; email: njackson@meu.org.uk; Mulvanny, Alex; email: amulvanny@meu.org.uk; Singh, Dave; email: dsingh@meu.org.uk (MDPI, 2021-09-27)
      Background: Chronic obstructive pulmonary disease (COPD) inflammatory endotypes are associated with different airway microbiomes. We used quantitative polymerase chain reaction (qPCR) analysis of sputum samples to establish the bacterial load upper limit in healthy controls; these values determined the bacterial colonisation prevalence in a longitudinal COPD cohort. Bacteriology combined with sputum inflammatory cells counts were used to investigate COPD endotypes. Methods: Sixty COPD patients and 15 healthy non-smoking controls were recruited. Sputum was analysed by qPCR (for Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae and Psuedomonas aeruginosa) and sputum differential cell counts at baseline and 6 months. Results: At baseline and 6 months, 23.1% and 25.6% of COPD patients were colonised with H. influenzae, while colonisation with other bacterial species was less common, e.g., S. pneumoniae—1.9% and 5.1%, respectively. H. influenzae + ve patients had higher neutrophil counts at baseline (90.1% vs. 67.3%, p 0.01), with similar results at 6 months. COPD patients with sputum eosinophil counts ≥3% at ≥1 visit rarely showed bacterial colonisation. Conclusions: The prevalence of H. influenzae colonisation was approximately 25%, with low colonisation for other bacterial species. H. influenzae colonisation was associated with sputum neutrophilia, while eosinophilic inflammation and H. influenzae colonisation rarely coexisted.
    • Alcohol misuse is associated with poor response to systemic therapies for psoriasis: findings from a prospective multicentre cohort study

      Iskandar, I.Y.K.; orcid: 0000-0002-8030-1908; email: ireny.iskandar@manchester.ac.uk; Lunt, M.; Thorneloe, R.J.; orcid: 0000-0002-7522-221X; Cordingley, L.; Griffiths, C.E.M.; orcid: 0000-0001-5371-4427; Ashcroft, D.M.; on behalf the British Association of Dermatologists Biologics and Immunomodulators Register and Psoriasis Stratification to Optimise Relevant Therapy Study Groups (2021-08-13)
      Summary: Background: Factors that might influence response to systemic treatment for moderate‐to‐severe psoriasis are varied, and generally, are poorly understood, aside from high bodyweight, suggesting that other unidentified factors may be relevant in determining response to treatment. The impact of alcohol misuse on treatment response has not been previously investigated. Objectives: To investigate whether alcohol misuse is associated with poor response to treatment for psoriasis. Methods: This was a prospective cohort study in which response to systemic therapies was assessed using the Psoriasis Area and Severity Index (PASI). The CAGE (Cut down, Annoyed, Guilty, Eye opener) questionnaire was used to screen for alcohol misuse. A multivariable factional polynomial linear regression model was used to examine factors associated with change in PASI between baseline and follow‐up. Results: The cohort comprised 266 patients (biologic cohort, n = 134; conventional systemic cohort, n = 132). For the entire cohort, the median (interquartile range) PASI improved from 13 (10·0–18·3) at baseline to 3 (1·0–7·5) during follow‐up. A higher CAGE score [regression coefficient: 1·40, 95% confidence interval (CI) 0·04–2·77]; obesity (1·84, 95% CI 0·48–3·20); and receiving a conventional systemic rather than a biologic therapy (4·39, 95% CI 2·84–5·95) were significantly associated with poor response to treatment; whereas a higher baseline PASI (–0·83, 95% CI –0·92 to –0·74) was associated with a better response to treatment. Conclusions: The poor response to therapy associated with alcohol misuse and obesity found in people with psoriasis calls for lifestyle behaviour change interventions and support as part of routine clinical care. Targeting interventions to prevent, detect and manage alcohol misuse among people with psoriasis is needed to minimize adverse health consequences and improve treatment response.
    • Altered protein O-GlcNAcylation in placentas from mothers with diabetes causes aberrant endocytosis in placental trophoblast cells

      Palin, Victoria; Russell, Matthew; Graham, Robert; Aplin, John D.; Westwood, Melissa; email: melissa.westwood@manchester.ac.uk (Nature Publishing Group UK, 2021-10-19)
      Abstract: Women with pre-existing diabetes have an increased risk of poor pregnancy outcomes, including disordered fetal growth, caused by changes to placental function. Here we investigate the possibility that the hexosamine biosynthetic pathway, which utilises cellular nutrients to regulate protein function via post-translationally modification with O-linked N-acetylglucosamine (GlcNAc), mediates the placental response to the maternal metabolic milieu. Mass spectrometry analysis revealed that the placental O-GlcNAcome is altered in women with type 1 (n = 6) or type 2 (n = 6) diabetes T2D (≥ twofold change in abundance in 162 and 165 GlcNAcylated proteins respectively compared to BMI-matched controls n = 11). Ingenuity pathway analysis indicated changes to clathrin-mediated endocytosis (CME) and CME-associated proteins, clathrin, Transferrin (TF), TF receptor and multiple Rabs, were identified as O-GlcNAcylation targets. Stimulating protein O-GlcNAcylation using glucosamine (2.5 mM) increased the rate of TF endocytosis by human placental cells (p = 0.02) and explants (p = 0.04). Differential GlcNAcylation of CME proteins suggests altered transfer of cargo by placentas of women with pre-gestational diabetes, which may contribute to alterations in fetal growth. The human placental O-GlcNAcome provides a resource to aid further investigation of molecular mechanisms governing placental nutrient sensing.
    • Alternative metabolic pathways and strategies to high-titre terpenoid production in

      Rinaldi, Mauro A; orcid: 0000-0001-7087-1184; Ferraz, Clara A; orcid: 0000-0003-2628-8412; Scrutton, Nigel S; orcid: 0000-0002-4182-3500 (2021-07-07)
      Covering: up to 2021Terpenoids are a diverse group of chemicals used in a wide range of industries. Microbial terpenoid production has the potential to displace traditional manufacturing of these compounds with renewable processes, but further titre improvements are needed to reach cost competitiveness. This review discusses strategies to increase terpenoid titres in Escherichia coli with a focus on alternative metabolic pathways. Alternative pathways can lead to improved titres by providing higher orthogonality to native metabolism that redirects carbon flux, by avoiding toxic intermediates, by bypassing highly-regulated or bottleneck steps, or by being shorter and thus more efficient and easier to manipulate. The canonical 2-C-methyl-d-erythritol 4-phosphate (MEP) and mevalonate (MVA) pathways are engineered to increase titres, sometimes using homologs from different species to address bottlenecks. Further, alternative terpenoid pathways, including additional entry points into the MEP and MVA pathways, archaeal MVA pathways, and new artificial pathways provide new tools to increase titres. Prenyl diphosphate synthases elongate terpenoid chains, and alternative homologs create orthogonal pathways and increase product diversity. Alternative sources of terpenoid synthases and modifying enzymes can also be better suited for E. coli expression. Mining the growing number of bacterial genomes for new bacterial terpenoid synthases and modifying enzymes identifies enzymes that outperform eukaryotic ones and expand microbial terpenoid production diversity. Terpenoid removal from cells is also crucial in production, and so terpenoid recovery and approaches to handle end-product toxicity increase titres. Combined, these strategies are contributing to current efforts to increase microbial terpenoid production towards commercial feasibility.