• The SCCS Scientific Advice on the Safety of Nanomaterials in Cosmetics

      Bernauer, Ulrike; Bodin, Laurent; Chaudhry, Qasim; Coenraads, Pieter Jan; Dusinska, Maria; Gaffet, Eric; Panteri, Eirini; Rogiers, Vera; Rousselle, Christophe; Stepnik, Maciej; et al.
      The Cosmetic Regulation (EC) No 1223/2009 specifically covers the risk of nanomaterials used in cosmetic products. If there are concerns regarding the safety of a nanomaterial, the European Commission refers it to the SCCS for a scientific opinion. The Commission mandated the SCCS to identify the scientific basis for safety concerns that could be used as a basis for identifying and prioritising nanomaterials for safety assessment, and to revisit previous inconclusive SCCS opinions on nanomaterials to identify any concerns for potential risks to the consumer health. The SCCS Scientific Advice identified the key general aspects of nanomaterials that should raise a safety concern for a safety assessor/manager, so that the nanomaterial(s) in question could be subjected to safety assessment to establish safety to the consumer. The Advice also developed a list of the nanomaterials notified to the Commission for use in cosmetics in an order of priority for safety assessment, and revisited three previous inconclusive opinions on nanomaterials to highlight concerns over consumer safety that merited further safety assessment.
    • The SCCS scientific advice on the safety of nanomaterials in cosmetics.

      SCCS members. Electronic address: SANTE-C2-SCCS@ec.europa.eu; Bernauer, Ulrike; Bodin, Laurent; Chaudhry, Qasim; Coenraads, Pieter Jan; Dusinska, Maria; Gaffet, Eric; Panteri, Eirini; Rogiers, Vera; Rousselle, Christophe; et al. (2021-09-22)
      The Cosmetic Regulation (EC) No 1223/2009 specifically covers the risk of nanomaterials used in cosmetic products. If there are concerns regarding the safety of a nanomaterial, the European Commission refers it to the SCCS for a scientific opinion. The Commission mandated the SCCS to identify the scientific basis for safety concerns that could be used as a basis for identifying and prioritising nanomaterials for safety assessment, and to revisit previous inconclusive SCCS opinions on nanomaterials to identify any concerns for potential risks to the consumer health. The SCCS Scientific Advice identified the key general aspects of nanomaterials that should raise a safety concern for a safety assessor/manager, so that the nanomaterial(s) in question could be subjected to safety assessment to establish safety to the consumer. The Advice also developed a list of the nanomaterials notified to the Commission for use in cosmetics in an order of priority for safety assessment, and revisited three previous inconclusive opinions on nanomaterials to highlight concerns over consumer safety that merited further safety assessment. [Abstract copyright: Copyright © 2021 Elsevier Inc. All rights reserved.]
    • The Th1 cell regulatory circuitry is largely conserved between human and mouse.

      Henderson, Stephen; orcid: 0000-0002-9032-3828; Pullabhatla, Venu; Hertweck, Arnulf; de Rinaldis, Emanuele; Herrero, Javier; orcid: 0000-0001-7313-717X; Lord, Graham M; orcid: 0000-0003-2069-4743; email: graham.lord@manchester.ac.uk; Jenner, Richard G; orcid: 0000-0002-2946-6811; email: r.jenner@ucl.ac.uk (2021-09-16)
      Gene expression programs controlled by lineage-determining transcription factors are often conserved between species. However, infectious diseases have exerted profound evolutionary pressure, and therefore the genes regulated by immune-specific transcription factors might be expected to exhibit greater divergence. T-bet (Tbx21) is the immune-specific, lineage-specifying transcription factor for T helper type I (Th1) immunity, which is fundamental for the immune response to intracellular pathogens but also underlies inflammatory diseases. We compared T-bet genomic targets between mouse and human CD4 T cells and correlated T-bet binding patterns with species-specific gene expression. Remarkably, we found that the majority of T-bet target genes are conserved between mouse and human, either via preservation of binding sites or via alternative binding sites associated with transposon-linked insertion. Species-specific T-bet binding was associated with differences in transcription factor-binding motifs and species-specific expression of associated genes. These results provide a genome-wide cross-species comparison of Th1 gene regulation that will enable more accurate translation of genetic targets and therapeutics from pre-clinical models of inflammatory and infectious diseases and cancer into human clinical trials. [Abstract copyright: © 2021 Henderson et al.]
    • The theoretical basis of a nationally implemented type 2 diabetes prevention programme: how is the programme expected to produce changes in behaviour?

      Hawkes, Rhiannon E; Miles, Lisa M; French, David P; orcid: 0000-0002-7663-7804; email: david.french@manchester.ac.uk (2021-05-13)
      <h4>Background</h4>It is considered best practice to provide clear theoretical descriptions of how behaviour change interventions should produce changes in behaviour. Commissioners of the National Health Service Diabetes Prevention Programme (NHS-DPP) specified that the four independent provider organisations must explicitly describe the behaviour change theory underpinning their interventions. The nationally implemented programme, launched in 2016, aims to prevent progression to Type 2 diabetes in high-risk adults through changing diet and physical activity behaviours. This study aimed to: (a) develop a logic model describing how the NHS-DPP is expected to work, and (b) document the behaviour change theories underpinning providers' NHS-DPP interventions.<h4>Methods</h4>A logic model detailing how the programme should work in changing diet and activity behaviours was extracted from information in three specification documents underpinning the NHS-DPP. To establish how each of the four providers expected their interventions to produce behavioural changes, information was extracted from their programme plans, staff training materials, and audio-recorded observations of mandatory staff training courses attended in 2018. All materials were coded using Michie and Prestwich's Theory Coding Scheme.<h4>Results</h4>The NHS-DPP logic model included information provision to lead to behaviour change intentions, followed by a self-regulatory cycle including action planning and monitoring behaviour. None of the providers described an explicit logic model of how their programme will produce behavioural changes. Two providers stated their programmes were informed by the COM-B (Capability Opportunity Motivation - Behaviour) framework, the other two described targeting factors from multiple theories such as Self-Regulation Theory and Self-Determination Theory. All providers cited examples of proposed links between some theoretical constructs and behaviour change techniques (BCTs), but none linked all BCTs to specified constructs. Some discrepancies were noted between the theory described in providers' programme plans and theory described in staff training.<h4>Conclusions</h4>A variety of behaviour change theories were used by each provider. This may explain the variation between providers in BCTs selected in intervention design, and the mismatch between theory described in providers' programme plans and staff training. Without a logic model describing how they expect their interventions to work, justification for intervention contents in providers' programmes is not clear.
    • The theoretical basis of a nationally implemented type 2 diabetes prevention programme: how is the programme expected to produce changes in behaviour?

      Hawkes, Rhiannon E.; Miles, Lisa M.; French, David P.; orcid: 0000-0002-7663-7804; email: David.French@manchester.ac.uk (BioMed Central, 2021-05-13)
      Abstract: Background: It is considered best practice to provide clear theoretical descriptions of how behaviour change interventions should produce changes in behaviour. Commissioners of the National Health Service Diabetes Prevention Programme (NHS-DPP) specified that the four independent provider organisations must explicitly describe the behaviour change theory underpinning their interventions. The nationally implemented programme, launched in 2016, aims to prevent progression to Type 2 diabetes in high-risk adults through changing diet and physical activity behaviours. This study aimed to: (a) develop a logic model describing how the NHS-DPP is expected to work, and (b) document the behaviour change theories underpinning providers’ NHS-DPP interventions. Methods: A logic model detailing how the programme should work in changing diet and activity behaviours was extracted from information in three specification documents underpinning the NHS-DPP. To establish how each of the four providers expected their interventions to produce behavioural changes, information was extracted from their programme plans, staff training materials, and audio-recorded observations of mandatory staff training courses attended in 2018. All materials were coded using Michie and Prestwich’s Theory Coding Scheme. Results: The NHS-DPP logic model included information provision to lead to behaviour change intentions, followed by a self-regulatory cycle including action planning and monitoring behaviour. None of the providers described an explicit logic model of how their programme will produce behavioural changes. Two providers stated their programmes were informed by the COM-B (Capability Opportunity Motivation – Behaviour) framework, the other two described targeting factors from multiple theories such as Self-Regulation Theory and Self-Determination Theory. All providers cited examples of proposed links between some theoretical constructs and behaviour change techniques (BCTs), but none linked all BCTs to specified constructs. Some discrepancies were noted between the theory described in providers’ programme plans and theory described in staff training. Conclusions: A variety of behaviour change theories were used by each provider. This may explain the variation between providers in BCTs selected in intervention design, and the mismatch between theory described in providers’ programme plans and staff training. Without a logic model describing how they expect their interventions to work, justification for intervention contents in providers’ programmes is not clear.
    • The theoretical basis of a nationally implemented type 2 diabetes prevention programme: how is the programme expected to produce changes in behaviour?

      Hawkes, Rhiannon E; Miles, Lisa M; French, David P; orcid: 0000-0002-7663-7804; email: david.french@manchester.ac.uk (2021-05-13)
      It is considered best practice to provide clear theoretical descriptions of how behaviour change interventions should produce changes in behaviour. Commissioners of the National Health Service Diabetes Prevention Programme (NHS-DPP) specified that the four independent provider organisations must explicitly describe the behaviour change theory underpinning their interventions. The nationally implemented programme, launched in 2016, aims to prevent progression to Type 2 diabetes in high-risk adults through changing diet and physical activity behaviours. This study aimed to: (a) develop a logic model describing how the NHS-DPP is expected to work, and (b) document the behaviour change theories underpinning providers' NHS-DPP interventions. A logic model detailing how the programme should work in changing diet and activity behaviours was extracted from information in three specification documents underpinning the NHS-DPP. To establish how each of the four providers expected their interventions to produce behavioural changes, information was extracted from their programme plans, staff training materials, and audio-recorded observations of mandatory staff training courses attended in 2018. All materials were coded using Michie and Prestwich's Theory Coding Scheme. The NHS-DPP logic model included information provision to lead to behaviour change intentions, followed by a self-regulatory cycle including action planning and monitoring behaviour. None of the providers described an explicit logic model of how their programme will produce behavioural changes. Two providers stated their programmes were informed by the COM-B (Capability Opportunity Motivation - Behaviour) framework, the other two described targeting factors from multiple theories such as Self-Regulation Theory and Self-Determination Theory. All providers cited examples of proposed links between some theoretical constructs and behaviour change techniques (BCTs), but none linked all BCTs to specified constructs. Some discrepancies were noted between the theory described in providers' programme plans and theory described in staff training. A variety of behaviour change theories were used by each provider. This may explain the variation between providers in BCTs selected in intervention design, and the mismatch between theory described in providers' programme plans and staff training. Without a logic model describing how they expect their interventions to work, justification for intervention contents in providers' programmes is not clear.
    • The top 10 research priorities in bleeding disorders: a James Lind Alliance Priority Setting Partnership

      Shapiro, Susan; orcid: 0000-0003-0402-0802; Stephensen, David; Camp, Charlotte; Carroll, Liz; Collins, Peter; Elston, Derek; Gallagher, Patrick; Khair, Kate; orcid: 0000-0003-2001-5958; McKeown, William; O'Hara, Jamie; et al. (Wiley, 2019-04-23)
    • The transatlantic evolution in understanding sudden cardiac death in athletes.

      Malhotra, Aneil; email: aneil.malhotra@manchester.ac.uk; Sivalokanathan, Sanjay (2021-07-06)
    • The ‘physician-athlete’ and the development of sports medicine as a ‘very peculiar practice’

      Waddington, Ivan; Brissonneau, Christophe (Informa UK Limited, 2022-05-03)
    • THEOLOGY AND THE PUBLIC SQUARE: MAPPING THE FIELD

      Graham, Elaine (Liverpool University Press, 2020-01)
    • Theorising the hospice gaze: A Foucauldian collaborative ethnography of a palliative day care service.

      Nagington, Maurice; email: maurice.nagington@manchester.ac.uk; Holman, David; Mumford, Clare; McCann, Leo (2021-10-08)
      Foucault's medical gaze has only been minimally applied to palliative care through the analysis of key policy documents. This paper develops the conceptualisation of Foucault's medical gaze using empirical data gathered from a group ethnography of a hospice daycare centre. Using Foucault's medical gaze as a theoretical aporia we conceptualise the "hospice gaze". We argue the hospice gaze is the antithesis of the Foucauldian medical gaze, suggesting it operates reflexively so that professionals adapt to patients, rather than patients to professionals; that it is directed towards enabling patients and their loved ones to narrate severe illness and death in ways that develop more patient-centred narratives; and, structures the processes of care in direct resistance to the neoliberalisation of healthcare by engaging in slow practices of care with patient's bodies and minds. Finally, key to all of this is how the hospice gaze manages the spaces of care to ensure that it always and already appears slow to the patients. Therefore, the hospice gaze ensures a (re)distribution of power and knowledge that minimises the corrosive qualities of busyness and maximises the ethical potentials of slowness. We conclude by arguing that the operation of the hospice gaze should be examined in other settings where palliative care is practiced such as in-patient and home care services. [Abstract copyright: Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.]
    • Tiagabine add-on therapy for drug-resistant focal epilepsy

      Bresnahan, Rebecca; Martin-McGill, Kirsty J; Hutton, Jane L; Marson, Anthony G (Wiley, 2019-10-14)
    • Tiagabine add-on therapy for drug-resistant focal epilepsy

      Bresnahan, Rebecca; Martin-McGill, Kirsty J; Hutton, Jane L; Marson, Anthony G (Wiley, 2019-10-14)
    • Tiagabine add-on therapy for drug-resistant focal epilepsy

      Bresnahan, Rebecca; Martin-McGill, Kirsty J; Hutton, Jane L; Marson, Anthony G (Wiley, 2019-10-14)
    • TIAM1-RAC1 promote small-cell lung cancer cell survival through antagonizing Nur77-induced BCL2 conformational change.

      Payapilly, Aishwarya; Guilbert, Ryan; Descamps, Tine; White, Gavin; Magee, Peter; Zhou, Cong; Kerr, Alastair; Simpson, Kathryn L; Blackhall, Fiona; Dive, Caroline; et al. (2021-11-09)
      Small-cell lung cancer (SCLC), an aggressive neuroendocrine malignancy, has limited treatment options beyond platinum-based chemotherapy, whereafter acquired resistance is rapid and common. By analyzing expression data from SCLC tumors, patient-derived models, and established cell lines, we show that the expression of TIAM1, an activator of the small GTPase RAC1, is associated with a neuroendocrine gene program. TIAM1 depletion or RAC1 inhibition reduces viability and tumorigenicity of SCLC cells by increasing apoptosis associated with conversion of BCL2 from its pro-survival to pro-apoptotic function via BH3 domain exposure. This conversion is dependent upon cytoplasmic translocation of Nur77, an orphan nuclear receptor. TIAM1 interacts with and sequesters Nur77 in SCLC cell nuclei and TIAM1 depletion or RAC1 inhibition promotes Nur77 translocation to the cytoplasm. Mutant TIAM1 with reduced Nur77 binding fails to suppress apoptosis triggered by TIAM1 depletion. In conclusion, TIAM1-RAC1 signaling promotes SCLC cell survival via Nur77 nuclear sequestration. [Abstract copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.]
    • Towards adoption of mobile data collection for effective adaptation and climate risk management in Africa

      Adekola, Olalekan; orcid: 0000-0001-9747-0583; email: o.adekola@yorksj.ac.uk; Lamond, Jessica; orcid: 0000-0001-8931-0192; Adelekan, Ibidun; orcid: 0000-0002-3407-8549; Bhattacharya‐Mis, Namrata; orcid: 0000-0003-4967-8325; Ekinya, Mboto; Bassey Eze, Eze; Ujoh, Fanan; orcid: 0000-0003-2554-0815 (2022-05-16)
      Abstract: The collection and use of data on climate change and its impacts are crucial for effective climate adaptation and climate risk management. The revolution in internet access, technology and costs has led to a shift from using traditional paper‐based data collection to the use of Mobile Data Collection using Personal Digital Assistants (PDA) such as smartphones and tablets. In this paper, we report our experiences using both approaches for a household and business survey during a climate adaptation study in two Nigerian cities—Makurdi and Calabar. The focus of this paper is to evaluate and compare the effectiveness of using traditional paper‐based data collection and PDAs as data collection tools for climate change study in African societies. In Calabar, data were collected using paper questionnaires, while in Makurdi the questionnaires were developed on Open Data Kit (ODK) and administered using PDAs. Results show that data collection using PDA was faster, cheaper, more accurate and resulted in fewer omissions than paper‐based data collection. There was a time saving of four (4) minutes per questionnaire and a 24% cost saving when using PDA. PDA provides additional benefits where platforms can collect images, videos and coordinates. This significantly improved the credibility of the data collection process and provided further data that allowed for the mapping of environmental phenomena by linking survey research with geo‐referenced data in a geographic information systems platform to provide spatial representations of social and environmental system convergence. PDA offers a tool for collecting data that will make necessary socio‐environmental data available in a faster, reliable and cheaper manner; future research can build on this study by discovering other possible but less highlighted benefits of PDA. Although, with great benefits, there are lessons to be learnt and issues to consider when deploying PDA in large‐scale household surveys.
    • Towards an improved prediction of concentrated antibody solution viscosity using the Huggins coefficient.

      Roche, Aisling; Gentiluomo, Lorenzo; Sibanda, Nicole; Roessner, Dierk; Friess, Wolfgang; Trainoff, Steven P; Curtis, Robin; email: r.curtis@manchester.ac.uk (2021-09-04)
      The viscosity of a monoclonal antibody solution must be monitored and controlled as it can adversely affect product processing, packaging and administration. Engineering low viscosity mAb formulations is challenging as prohibitive amounts of material are required for concentrated solution analysis, and it is difficult to predict viscosity from parameters obtained through low-volume, high-throughput measurements such as the interaction parameter, k , and the second osmotic virial coefficient, B . As a measure encompassing the effect of intermolecular interactions on dilute solution viscosity, the Huggins coefficient, k , is a promising candidate as a parameter measureable at low concentrations, but indicative of concentrated solution viscosity. In this study, a differential viscometry technique is developed to measure the intrinsic viscosity, [η], and the Huggins coefficient, k , of protein solutions. To understand the effect of colloidal protein-protein interactions on the viscosity of concentrated protein formulations, the viscometric parameters are compared to k and B of two mAbs, tuning the contributions of repulsive and attractive forces to the net protein-protein interaction by adjusting solution pH and ionic strength. We find a strong correlation between the concentrated protein solution viscosity and the k but this was not observed for the k or the b , which have been previously used as indicators of high concentration viscosity. Trends observed in [η] and k values as a function of pH and ionic strength are rationalised in terms of protein-protein interactions. [Abstract copyright: Copyright © 2021. Published by Elsevier Inc.]