• <i>meta</i>-Selective olefination of fluoroarenes with alkynes using CO<sub>2</sub> as a traceless directing group.

      Spencer, Andrew R A; Korde, Rishi; Font, Marc; Larrosa, Igor; orcid: 0000-0002-5391-7424 (2020-03-31)
      Over the last few decades C-H olefination has received significant interest, due to the importance and usefulness of aryl olefins both as synthetic targets and intermediates. While a wide range of <i>ortho</i>-olefination protocols have been developed, only a small number of <i>meta</i>-olefinations are currently available. Importantly, the most common approach to <i>meta</i>-olefination, using a large <i>meta</i>-directing template, is not suitable for substrates such as fluorobenzenes, which cannot be derivatised. We report that the <i>meta</i>-selective olefination of fluoroarenes can be achieved <i>via</i> the use of CO<sub>2</sub> as a traceless directing group, which can be easily installed and removed in a one-pot process. Furthermore, this approach avoids the use of stoichiometric Ag(i)-salts, commonly used in C-H olefinations, and affords complete <i>meta</i>- over <i>ortho</i>/<i>para</i>-regioselectivity.
    • <i>Ortho</i> C-H arylation of arenes at room temperature using visible light ruthenium C-H activation.

      Sagadevan, Arunachalam; orcid: 0000-0001-9486-1706; Charitou, Anastasios; orcid: 0000-0002-9100-8950; Wang, Fen; Ivanova, Maria; Vuagnat, Martin; Greaney, Michael F; orcid: 0000-0001-9633-1135 (2020-04-07)
      A ruthenium-catalyzed <i>ortho</i> C-H arylation process is described using visible light. Using the readily available catalyst [RuCl<sub>2</sub>(<i>p</i>-cymene)]<sub>2</sub>, visible light irradiation was found to enable arylation of 2-aryl-pyridines at room temperature for a range of aryl bromides and iodides.
    • <i>‘I call it the hero complex’ –</i> Critical considerations of power and privilege and seeking to be an agent of change in qualitative researchers’ experiences

      Oakley, Lisa; orcid: 0000-0001-8909-7889; Fenge, Lee-Ann; orcid: 0000-0003-0896-7323; Taylor, Bethan (Informa UK Limited, 2020-01-30)
    • Ice-templated hybrid graphene oxide—graphene nanoplatelet lamellar architectures: tuning mechanical and electrical properties

      Yang, Pei; orcid: 0000-0002-4639-2076; Tontini, Gustavo; orcid: 0000-0002-2453-6358; email: gustavotontini@gmail.com; Wang, Jiacheng; orcid: 0000-0001-7301-3310; Kinloch, Ian A; orcid: 0000-0003-3314-6869; Barg, Suelen; orcid: 0000-0002-0723-7081; email: Suelen.Barg@manchester.ac.uk (IOP Publishing, 2021-02-23)
      Abstract: The traditional freeze-casting route for processing graphene-based aerogels is generally restricted to aqueously dispersed flakes of graphene oxide (GO) and post-processing reduction treatments, which brings restrictions to the aerogels electrical properties. In this work, we report a versatile aqueous processing route that uses the ability of GO todisperse graphene nanoplatelets (GNP) to produce rGO-GNP lamellar aerogels via unidirectional freeze-casting. In order to optimise the properties of the aerogel, GO-GNP dispersions were partially reduced by L-ascorbic acid prior to freeze-casting to tune the carbon and oxygen (C/O) ratio. The aerogels were then heat treated after casting to fully reduce the GO. The chemical reduction time was found to control the microstructure of the resulting aeorgels and thus to tune their electrical and mechanical properties. An rGO-GNP lamellar aerogel with density of 20.8 ± 0.8 mg cm−3 reducing using a reduction of 60 min achieved an electrical conductivity of 42.3 S m−1. On the other hand, an optimal reduction time of 35 min led to an aerogel with compressive modulus of 0.51 ±0.06 MPa at a density of 23.2 ± 0.7 mg cm−3, revealing a compromise between the tuning of electrical and mechanical properties. We show the present processing route can also be easily applied to produce lamellar aerogels on other graphene-based materials such as electrochemically exfoliated graphene.
    • Ice-templated hybrid graphene oxide—graphene nanoplatelet lamellar architectures: tuning mechanical and electrical properties

      Yang, Pei; orcid: 0000-0002-4639-2076; Tontini, Gustavo; orcid: 0000-0002-2453-6358; email: gustavotontini@gmail.com; Wang, Jiacheng; orcid: 0000-0001-7301-3310; Kinloch, Ian A; orcid: 0000-0003-3314-6869; Barg, Suelen; orcid: 0000-0002-0723-7081; email: Suelen.Barg@manchester.ac.uk (IOP Publishing, 2021-02-23)
      Abstract: The traditional freeze-casting route for processing graphene-based aerogels is generally restricted to aqueously dispersed flakes of graphene oxide (GO) and post-processing reduction treatments, which brings restrictions to the aerogels electrical properties. In this work, we report a versatile aqueous processing route that uses the ability of GO todisperse graphene nanoplatelets (GNP) to produce rGO-GNP lamellar aerogels via unidirectional freeze-casting. In order to optimise the properties of the aerogel, GO-GNP dispersions were partially reduced by L-ascorbic acid prior to freeze-casting to tune the carbon and oxygen (C/O) ratio. The aerogels were then heat treated after casting to fully reduce the GO. The chemical reduction time was found to control the microstructure of the resulting aeorgels and thus to tune their electrical and mechanical properties. An rGO-GNP lamellar aerogel with density of 20.8 ± 0.8 mg cm−3 reducing using a reduction of 60 min achieved an electrical conductivity of 42.3 S m−1. On the other hand, an optimal reduction time of 35 min led to an aerogel with compressive modulus of 0.51 ±0.06 MPa at a density of 23.2 ± 0.7 mg cm−3, revealing a compromise between the tuning of electrical and mechanical properties. We show the present processing route can also be easily applied to produce lamellar aerogels on other graphene-based materials such as electrochemically exfoliated graphene.
    • Identification of an Altered Matrix Signature in Kidney Aging and Disease.

      Randles, Michael; Lausecker, Franziska; Kong, Qing; Suleiman, Hani; Reid, Graeme; Kolatsi-Joannou, Maria; Tian, Pinyuan; Falcone, Sara; Davenport, Bernard; Potter, Paul; et al. (2021-05-28)
      Accumulation of extracellular matrix in organs and tissues is a feature of both aging and disease. In the kidney, glomerulosclerosis and tubulointerstitial fibrosis accompany the decline in function, which current therapies cannot address, leading to organ failure. Whilst histological and ultrastructural patterns of excess matrix form the basis of human disease classifications, comprehensive molecular resolution of abnormal matrix is lacking. Using mass spectrometry-based proteomics we resolved matrix composition over age in mouse models of kidney disease. We compared the changes in mice with a global characterization of human kidney matrix during aging and to existing kidney disease datasets to identify common molecular features. Ultrastructural changes in basement membranes are associated with altered cell adhesion and metabolic processes and with distinct matrix proteomes during aging and kidney disease progression in mice. Within the altered matrix, basement membrane components (laminins, type IV collagen, type XVIII collagen) were reduced and interstitial matrix proteins (collagens I, III, VI, XV, fibrinogens and nephronectin) were increased, a pattern also seen in human kidney aging. Indeed, this signature of matrix proteins was consistently modulated across all age and disease comparisons and the increase in interstitial matrix was also observed in human kidney disease datasets. This study provides deep molecular resolution of matrix accumulation in kidney aging and disease and identifies a common signature of proteins that provides insight into mechanisms of response to kidney injury and repair.
    • Identification of factors associated with stillbirth in Zimbabwe – a cross sectional study

      Dube, Kushupika; email: kushupika.dube@postgrad.manchester.ac.uk; Lavender, Tina; Blaikie, Kieran; Sutton, Christopher J.; Heazell, Alexander E. P.; Smyth, Rebecca M. D. (BioMed Central, 2021-09-29)
      Abstract: Introduction: 98% of the 2.6 million stillbirths per annum occur in low and middle income countries. However, understanding of risk factors for stillbirth in these settings is incomplete, hampering efforts to develop effective strategies to prevent deaths. Methods: A cross-sectional study of eligible women on the postnatal ward at Mpilo Hospital, Zimbabwe was undertaken between 01/08/2018 and 31/03/2019 (n = 1779). Data were collected from birth records for maternal characteristics, obstetric and past medical history, antenatal care and pregnancy outcome. A directed acyclic graph was constructed with multivariable logistic regression performed to fit the corresponding model specification to data comprising singleton pregnancies, excluding neonatal deaths (n = 1734), using multiple imputation for missing data. Where possible, findings were validated against all women with births recorded in the hospital birth register (n = 1847). Results: Risk factors for stillbirth included: previous stillbirth (29/1691 (2%) of livebirths and 39/43 (91%) of stillbirths, adjusted Odds Ratio (aOR) 2628.9, 95% CI 342.8 to 20,163.0), antenatal care (aOR 44.49 no antenatal care vs. > 4 antenatal care visits, 95% CI 6.80 to 291.19), maternal medical complications (aOR 7.33, 95% CI 1.99 to 26.92) and season of birth (Cold season vs. Mild aOR 14.29, 95% CI 3.09 to 66.08; Hot season vs. Mild aOR 3.39, 95% CI 0.86 to 13.27). Women who had recurrent stillbirth had a lower educational and health status (18.2% had no education vs. 10.0%) and were less likely to receive antenatal care (20.5% had no antenatal care vs. 6.6%) than women without recurrent stillbirth. Conclusion: The increased risk in women who have a history of stillbirth is a novel finding in Low and Middle Income Countries (LMICs) and is in agreement with findings from High Income Countries (HICs), although the estimated effect size is much greater (OR in HICs ~ 5). Developing antenatal care for this group of women offers an important opportunity for stillbirth prevention.
    • Identifying Targets for Interventions to Increase Uptake and Use of Hearing Protection in Noisy Recreational Settings

      Loughran, Michael T.; email: michael.loughran@manchester.ac.uk; Plack, Christopher J.; orcid: 0000-0002-2987-5332; email: chris.plack@manchester.ac.uk; Armitage, Christopher J.; orcid: 0000-0003-2365-1765; email: chris.armitage@manchester.ac.uk (MDPI, 2021-07-29)
      Interventions to increase hearing protection behaviours within noisy recreational settings are limited by the lack of an underpinning evidence base. The aim of the present study was to identify targets for interventions in a population exposed to recreational noise, including those who had used hearing protection (ever-performers) versus those who had not (never-performers). A cross-sectional survey was administered to 185 UK adults who had been involved in noisy recreational activities. Participants had an average age of 36.79 years; the majority were women (68.1%), from a white ethnic background (87.6%), and with non-manual occupations (75.7%). Using Chi-square, MANOVA and ANOVA, we looked for differences in sociodemographic variables and variables from the capabilities, opportunities and motivations model of behaviour change (COM-B) between ever- and never-performers. Ever-performers were more likely to be younger (p 0.050), men (p 0.050), and in a manual occupation (p 0.050) compared to never-performers. Although the two groups felt capable and reported similar opportunities to use hearing protection, never-performers lacked automatic motivation (p 0.001) and reflective motivation (p 0.001) compared to ever-performers. For the first time, the present study identifies potential groups at whom hearing protection interventions might be targeted and what those interventions may contain. Further work is required to develop interventions targeted at older people, women and those in non-manual occupations. Lack of motivation is a key concern, and further work that uses specific theoretical frameworks, such as the PRIME (Plans, Responses, Impulses, Motives, and Evaluations) theory of motivation, may shed light on the kinds of interventions that are needed to boost hearing protection use effectively.
    • Identifying the content and context of pain within paediatric rheumatology healthcare professional curricula in the UK: a summative content analysis

      Lee, Rebecca Rachael; orcid: 0000-0002-4559-1647; email: rebecca.lee-4@manchester.ac.uk; McDonagh, Janet E.; Connelly, Mark; Peters, Sarah; Cordingley, Lis (BioMed Central, 2021-08-21)
      Abstract: Background: The curriculum for professionals working in paediatric rheumatology should include pain but it is unclear to what extent this currently occurs. The aim of this study was to identify pain-related curriculum content and the context in which pain is presented in educational and training documentation for healthcare professionals in this clinical speciality. Methods: Core curricula documents from UK based professional organisations were identified in partnership with healthcare professionals. Documents were analysed using a summative content analysis approach. Key pain terms were quantified and weighted frequencies were used to explore narrative pain themes. Latent content was interpreted qualitatively to explore the context within which pain terms were positioned. Results: Nine curriculum documents were identified and analysed from doctors, nurses, physiotherapists and occupational therapists specialising in paediatric rheumatology. Pain themes represented a mean percentage of 1.51% of text across all documents. Pain was rarely presented in the context of both inflammatory and non-inflammatory condition types despite being a common feature of each. Musculoskeletal pain was portrayed simply as a ‘somatic’ symptom, rather than as a complex phenomenon involving biological and psychosocial processes. Content around the assessment and management of pain was vague and inexplicit. Conclusion: Current educational and training documentation in paediatric rheumatology do not include core pain topics. Curricula for these healthcare professionals would benefit from updates in contemporary pain theories and examples of in-context, evidence-based pain practices. This should be a priority starting point for optimising patient pain care in paediatric musculoskeletal healthcare.
    • Identifying the content and context of pain within paediatric rheumatology healthcare professional curricula in the UK: a summative content analysis.

      Lee, Rebecca Rachael; orcid: 0000-0002-4559-1647; email: rebecca.lee-4@manchester.ac.uk; McDonagh, Janet E; Connelly, Mark; Peters, Sarah; Cordingley, Lis (2021-08-21)
      <h4>Background</h4>The curriculum for professionals working in paediatric rheumatology should include pain but it is unclear to what extent this currently occurs. The aim of this study was to identify pain-related curriculum content and the context in which pain is presented in educational and training documentation for healthcare professionals in this clinical speciality.<h4>Methods</h4>Core curricula documents from UK based professional organisations were identified in partnership with healthcare professionals. Documents were analysed using a summative content analysis approach. Key pain terms were quantified and weighted frequencies were used to explore narrative pain themes. Latent content was interpreted qualitatively to explore the context within which pain terms were positioned.<h4>Results</h4>Nine curriculum documents were identified and analysed from doctors, nurses, physiotherapists and occupational therapists specialising in paediatric rheumatology. Pain themes represented a mean percentage of 1.51% of text across all documents. Pain was rarely presented in the context of both inflammatory and non-inflammatory condition types despite being a common feature of each. Musculoskeletal pain was portrayed simply as a 'somatic' symptom, rather than as a complex phenomenon involving biological and psychosocial processes. Content around the assessment and management of pain was vague and inexplicit.<h4>Conclusion</h4>Current educational and training documentation in paediatric rheumatology do not include core pain topics. Curricula for these healthcare professionals would benefit from updates in contemporary pain theories and examples of in-context, evidence-based pain practices. This should be a priority starting point for optimising patient pain care in paediatric musculoskeletal healthcare.
    • Identity, Culture and Belonging: Educating Young Children for a Changing World

      Power, Michael; orcid: 0000-0002-9926-094X (Informa UK Limited, 2020-08-24)
    • Identity, Culture and Belonging: Educating Young Children for a Changing World

      Power, Michael; orcid: 0000-0002-9926-094X (Informa UK Limited, 2020-08-24)
    • Identity, Culture and Belonging: Educating Young Children for a Changing World

      Power, Michael; orcid: 0000-0002-9926-094X (Informa UK Limited, 2020-08-24)
    • IDPs in the Kurdistan Region of Iraq (KRI): Intractable Return and Absence of Social Integration Policy

      Khedir, Hewa Haji; orcid: 0000-0001-5257-2439; email: hewa.khedir@winchester.ac.uk (2020-05-27)
      Abstract: This paper examines the protracted nature of displacement in the Iraqi context and places emphasis on the need for a social integration policy to bridge the deep cleavages of Iraqi society. Methodologically, the paper utilizes qualitative data by conducting focus‐group discussions with IDPs and semi‐structured individual interviews in KRI. In terms of return possibilities, while return in many ways is perceived to be not practical and to involve future risks, research findings show that a community‐based distinction needs to be made between IDPs from minority backgrounds and IDPs who belong to demographic majorities in the homeland locations. A second distinction is a geographic and political one as findings indicate that IDPs who take refuge in KRI, though remain largely dissatisfied with displacement conditions, are willing to stay in KRI longer in the hope of further security and reconstruction process in the violence‐affected areas. With respect to social integration policy, the paper outlines institutional, political and cultural explanations for a virtually absolute absence of social integration policy on national and regional levels. The paper suggests that the proposed social integration policy can capitalize practical implications of Social Contact Theory (SCT) in enhancing the integration of IDPs in the host communities.
    • ILC3s control airway inflammation by limiting T cell responses to allergens and microbes.

      Teng, Fei; Tachó-Piñot, Roser; Sung, Biin; Farber, Donna L; Worgall, Stefan; Hammad, Hamida; Lambrecht, Bart N; Hepworth, Matthew R; email: matthew.hepworth@manchester.ac.uk; Sonnenberg, Gregory F; email: gfsonnenberg@med.cornell.edu (2021-11-23)
      Group 3 innate lymphoid cells (ILC3s) critically regulate host-microbe interactions in the gastrointestinal tract, but their role in the airway remains poorly understood. Here, we demonstrate that lymphoid-tissue-inducer (LTi)-like ILC3s are enriched in the lung-draining lymph nodes of healthy mice and humans. These ILC3s abundantly express major histocompatibility complex class II (MHC class II) and functionally restrict the expansion of allergen-specific CD4 T cells upon experimental airway challenge. In a mouse model of house-dust-mite-induced allergic airway inflammation, MHC class II ILC3s limit T helper type 2 (Th2) cell responses, eosinophilia, and airway hyperresponsiveness. Furthermore, MHC class II ILC3s limit a concomitant Th17 cell response and airway neutrophilia. This exacerbated Th17 cell response requires exposure of the lung to microbial stimuli, which can be found associated with house dust mites. These findings demonstrate a critical role for antigen-presenting ILC3s in orchestrating immune tolerance in the airway by restricting pro-inflammatory T cell responses to both allergens and microbes. [Abstract copyright: Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.]
    • Imaging translocator protein expression with positron emission tomography.

      Wimberley, Catriona; Buvat, Irene; Boutin, Hervé; email: herve.boutin@manchester.ac.uk (2021-11-03)
    • Immersive Virtual Reality for the Cognitive Rehabilitation of Stroke Survivors

      Chatterjee, Kausik; orcid: 0000-0002-3093-1469; Buchanan, Alastair; Cottrell, Katy; orcid: 0000-0002-1418-7676; Hughes, Sara; orcid: 0000-0001-6510-5960; Day, Thomas W.; orcid: 0000-0002-9153-4862; John, Nigel W.; orcid: 0000-0001-5153-182X (Institute of Electrical and Electronics Engineers (IEEE), 2022)
    • Immune infiltrate diversity confers a good prognosis in follicular lymphoma.

      Tsakiroglou, Anna-Maria; Astley, Susan; Dave, Manàs; Fergie, Martin; Harkness, Elaine; Rosenberg, Adeline; Sperrin, Matthew; West, Catharine; Byers, Richard; orcid: 0000-0003-0796-0365; email: richard.byers@mft.nhs.uk; Linton, Kim; email: kim.linton@manchester.ac.uk (2021-04-30)
      Follicular lymphoma (FL) prognosis is influenced by the composition of the tumour microenvironment. We tested an automated approach to quantitatively assess the phenotypic and spatial immune infiltrate diversity as a prognostic biomarker for FL patients. Diagnostic biopsies were collected from 127 FL patients initially treated with rituximab-based therapy (52%), radiotherapy (28%), or active surveillance (20%). Tissue microarrays were constructed and stained using multiplex immunofluorescence (CD4, CD8, FOXP3, CD21, PD-1, CD68, and DAPI). Subsequently, sections underwent automated cell scoring and analysis of spatial interactions, defined as cells co-occurring within 30 μm. Shannon's entropy, a metric describing species biodiversity in ecological habitats, was applied to quantify immune infiltrate diversity of cell types and spatial interactions. Immune infiltrate diversity indices were tested in multivariable Cox regression and Kaplan-Meier analysis for overall (OS) and progression-free survival (PFS). Increased diversity of cell types (HR = 0.19 95% CI 0.06-0.65, p = 0.008) and cell spatial interactions (HR = 0.39, 95% CI 0.20-0.75, p = 0.005) was associated with favourable OS, independent of the Follicular Lymphoma International Prognostic Index. In the rituximab-treated subset, the favourable trend between diversity and PFS did not reach statistical significance. Multiplex immunofluorescence and Shannon's entropy can objectively quantify immune infiltrate diversity and generate prognostic information in FL. This automated approach warrants validation in additional FL cohorts, and its applicability as a pre-treatment biomarker to identify high-risk patients should be further explored. The multiplex image dataset generated by this study is shared publicly to encourage further research on the FL microenvironment.
    • Immunomodulation by radiotherapy in tumour control and normal tissue toxicity.

      Cytlak, Urszula M; orcid: 0000-0002-2536-6012; email: urszula.cytlak-chaudhuri@manchester.ac.uk; Dyer, Douglas P; orcid: 0000-0001-5567-6241; Honeychurch, Jamie; orcid: 0000-0001-6938-0839; Williams, Kaye J; Travis, Mark A; orcid: 0000-0002-8485-2272; email: mark.travis-2@manchester.ac.uk; Illidge, Timothy M; orcid: 0000-0003-3191-7324; email: tim.illidge@manchester.ac.uk (2021-07-01)
      Radiotherapy (RT) is a highly effective anticancer treatment that is delivered to more than half of all patients with cancer. In addition to the well-documented direct cytotoxic effects, RT can have immunomodulatory effects on the tumour and surrounding tissues. These effects are thought to underlie the so-called abscopal responses, whereby RT generates systemic antitumour immunity outside the irradiated tumour. The full scope of these immune changes remains unclear but is likely to involve multiple components, such as immune cells, the extracellular matrix, endothelial and epithelial cells and a myriad of chemokines and cytokines, including transforming growth factor-β (TGFβ). In normal tissues exposed to RT during cancer therapy, acute immune changes may ultimately lead to chronic inflammation and RT-induced toxicity and organ dysfunction, which limits the quality of life of survivors of cancer. Here we discuss the emerging understanding of RT-induced immune effects with particular focus on the lungs and gut and the potential immune crosstalk that occurs between these tissues.
    • Impact failure in two silicates revealed by ultrafast, in situ, synchrotron X-ray microscopy

      Bourne, N. K.; email: neil.bourne@manchester.ac.uk; Mirihanage, W. U.; Olbinado, M. P.; Rack, A.; Rau, C. (Nature Publishing Group UK, 2020-06-25)
      Abstract: To travel safely behind screens that can protect us from stones and hail, we must understand the response of glass to impact. However, without a means to observe the mechanisms that fail different silicate architectures, engineering has relied on external sensors, post-impact examination and best-guess to glaze our vehicles. We have used single and multi-bunch, X-ray imaging to differentiate distinct phases of failure in two silicates. We identified distinct micromechanisms, operating in tandem and leading to failure in borosilicate glass and Z-cut quartz. A surface zone in the amorphous glass densifies before bulk fracture occurs and then fails the block, whilst in quartz, fast cracks, driven down cleavage planes, fails the bulk. Varying the rate at which ejecta escapes by using different indenter tip geometries controls the failed target’s bulk strength. This opens the way to more physically based constitutive descriptions for the glasses allowing design of safer, composite panels by controlling the impulses felt by protective screens.