• The Role of the Body Clock in Asthma and COPD: Implication for Treatment

      Krakowiak, Karolina; Durrington, Hannah J.; orcid: 0000-0002-9990-9446; email: hannah.durrington@manchester.ac.uk (Springer Healthcare Communications, 2018-06-01)
      Abstract: Asthma exhibits a marked time of day variation in symptoms, airway physiology, and airway inflammation. This is also seen in chronic obstructive pulmonary disease (COPD), but to a lesser extent. Our understanding of how physiological daily rhythms are regulated by the circadian clock is increasing, and there is growing evidence that the molecular clock is important in the pathogenesis of these two airway diseases. If time of day is important, then it follows that treatment of asthma and COPD should also be tailored to the most efficacious time of the day, a concept known as ‘chronotherapy’. There have been a number of studies to determine the optimal time of day at which to take medications for asthma and COPD. Some of these agents are already used ‘chronotherapeutically’ in practice (often at night-time). However, several studies investigating systemic and inhaled corticosteroids have consistently shown that the best time of day to take these medications for treating asthma is in the afternoon or early evening and not in the morning, when these medications are often prescribed. Future, large, randomized, placebo-controlled studies of systemic and inhaled corticosteroids in asthma and COPD are needed to inform clinical practice. Digital Features: This article is published with a graphical abstract to facilitate understanding of the article. To view digital features for this article go to the Supplementary Information of the article.
    • The Role of the European Society of Human Genetics in Delivering Genomic Education

      Tobias, Edward S.; Avram, Elena; Calapod, Patricia; Cordier, Christophe; den Dunnen, Johan T.; Ding, Can; Dolzan, Vita; Houge, Sofia Douzgou; Lynch, Sally Ann; O’Byrne, James; et al. (Frontiers Media S.A., 2021-09-03)
      The European Society of Human Genetics (ESHG) was founded in 1967 as a professional organisation for members working in genetics in clinical practice, research and education. The Society seeks the integration of scientific research and its implementation into clinical practice and the education of specialists and the public in all areas of medical and human genetics. The Society works to do this through many approaches, including educational sessions at the annual conference; training courses in general and specialist areas of genetics; an online resource of educational materials (EuroGEMS); and a mentorship scheme. The ESHG Education Committee is implementing new approaches to expand the reach of its educational activities and portfolio. With changes in technology, appreciation of the utility of genomics in healthcare and the public’s and patients’ increased awareness of the role of genomics, this review will summarise how the ESHG is adapting to deliver innovative educational activity.
    • 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

      Bernauer, Ulrike; Bodin, Laurent; orcid: 0000-0002-6900-8874; Chaudhry, Qasim; Coenraads, Pieter Jan; orcid: 0000-0001-9458-7129; Dusinska, Maria; Gaffet, Eric; orcid: 0000-0002-6451-3011; Panteri, Eirini; orcid: 0000-0003-3190-0127; Rogiers, Vera; Rousselle, Christophe; orcid: 0000-0003-0460-6192; Stepnik, Maciej; orcid: 0000-0003-1586-2482; et al. (Elsevier, 2021-09-28)
      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 supervisor conundrum

      Knight, Kate H; Leigh, Jacqueline; Whaley, Victoria; Rabie, Gay; Matthews, Marie; Doyle, Kate (Mark Allen Group, 2021-11-11)
    • The supervisor conundrum.

      Knight, Kate H; Leigh, Jacqueline; Whaley, Victoria; Rabie, Gay; Matthews, Marie; Doyle, Kate (2021-11-11)
    • The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival

      Valpione, Sara; Mundra, Piyushkumar A.; Galvani, Elena; Campana, Luca G.; orcid: 0000-0002-8466-8459; Lorigan, Paul; orcid: 0000-0002-8875-2164; De Rosa, Francesco; orcid: 0000-0003-0511-1298; Gupta, Avinash; Weightman, John; Mills, Sarah; Dhomen, Nathalie; et al. (Nature Publishing Group UK, 2021-07-02)
      Abstract: Tumor infiltration by T cells is paramount for effective anti-cancer immune responses. We hypothesized that the T cell receptor (TCR) repertoire of tumor infiltrating T lymphocytes could therefore be indicative of the functional state of these cells and determine disease course at different stages in cancer progression. Here we show that the diversity of the TCR of tumor infiltrating T cell at baseline is prognostic in various cancers, whereas the TCR clonality of T cell infiltrating metastatic melanoma pre-treatment is predictive for activity and efficacy of PD1 blockade immunotherapy.
    • The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival

      Valpione, Sara; Mundra, Piyushkumar A.; Galvani, Elena; Campana, Luca G.; orcid: 0000-0002-8466-8459; Lorigan, Paul; orcid: 0000-0002-8875-2164; De Rosa, Francesco; orcid: 0000-0003-0511-1298; Gupta, Avinash; Weightman, John; Mills, Sarah; Dhomen, Nathalie; et al. (Nature Publishing Group UK, 2021-07-02)
      Abstract: Tumor infiltration by T cells is paramount for effective anti-cancer immune responses. We hypothesized that the T cell receptor (TCR) repertoire of tumor infiltrating T lymphocytes could therefore be indicative of the functional state of these cells and determine disease course at different stages in cancer progression. Here we show that the diversity of the TCR of tumor infiltrating T cell at baseline is prognostic in various cancers, whereas the TCR clonality of T cell infiltrating metastatic melanoma pre-treatment is predictive for activity and efficacy of PD1 blockade immunotherapy.
    • The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival

      Valpione, Sara; Mundra, Piyushkumar A.; Galvani, Elena; Campana, Luca G.; orcid: 0000-0002-8466-8459; Lorigan, Paul; orcid: 0000-0002-8875-2164; De Rosa, Francesco; orcid: 0000-0003-0511-1298; Gupta, Avinash; Weightman, John; Mills, Sarah; Dhomen, Nathalie; et al. (Nature Publishing Group UK, 2021-07-02)
      Abstract: Tumor infiltration by T cells is paramount for effective anti-cancer immune responses. We hypothesized that the T cell receptor (TCR) repertoire of tumor infiltrating T lymphocytes could therefore be indicative of the functional state of these cells and determine disease course at different stages in cancer progression. Here we show that the diversity of the TCR of tumor infiltrating T cell at baseline is prognostic in various cancers, whereas the TCR clonality of T cell infiltrating metastatic melanoma pre-treatment is predictive for activity and efficacy of PD1 blockade immunotherapy.
    • The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival.

      Valpione, Sara; Mundra, Piyushkumar A; Galvani, Elena; Campana, Luca G; orcid: 0000-0002-8466-8459; Lorigan, Paul; orcid: 0000-0002-8875-2164; De Rosa, Francesco; orcid: 0000-0003-0511-1298; Gupta, Avinash; Weightman, John; Mills, Sarah; Dhomen, Nathalie; et al. (2021-07-02)
      Tumor infiltration by T cells is paramount for effective anti-cancer immune responses. We hypothesized that the T cell receptor (TCR) repertoire of tumor infiltrating T lymphocytes could therefore be indicative of the functional state of these cells and determine disease course at different stages in cancer progression. Here we show that the diversity of the TCR of tumor infiltrating T cell at baseline is prognostic in various cancers, whereas the TCR clonality of T cell infiltrating metastatic melanoma pre-treatment is predictive for activity and efficacy of PD1 blockade immunotherapy.
    • The taking place of older age

      Barron, Amy; orcid: 0000-0003-2547-9305; email: amy.barron@manchester.ac.uk (SAGE Publications, 2021-06-02)
      Representations of older age are often reductive in western societies, portrayed as a distinct period of life characterised by social disengagement and physiological decline. Through rich ethnographic accounts developed with older people from Greater Manchester UK, this paper is concerned with how the category of older age is made through representations, and the different ways people encounter and relate to it. In doing so, it disrupts reductive representations by considering how older age is lived. I respond to calls for the incorporation of more-than-representational and affective approaches into the geographic study of older age to advance research on ageing and highlight affect as a useful concept for thinking through difference. The paper is concerned with how older people are represented, with how representations differentially affect and are affected by older individuals, and with how representations of older age are performed and folded into lived accounts. More-than-representational theories offer an understanding of older age that is not pre-given or free-standing, but as something which can emerge, gather and disperse in relation with materialities as well as diffuse atmospheres, affects and emotional resonances.
    • The Temporal Uses of Moral Things: Manifesting, Anchoring and Conserving Caring Relations within the Sensorium

      Balmer, Andrew; orcid: 0000-0002-7146-0448; email: andrew.balmer@manchester.ac.uk; Meckin, Robert; Abbott, Owen (SAGE Publications, 2020-12-04)
      In this article we argue that menthol-containing products, like chewing gums, vapour rubs and mouthwashes, are used as moral things within everyday practices. They take on moral functions because of how their material qualities contribute to sensory experiences. Specifically, we focus on scenarios in which menthol products become associated with the moral work of care and highlight the temporal dimension of what people do with moral things. We review the literature on morality as a practical, everyday accomplishment and stress the embodied nature of caring practices to outline how care is bound up with sensory experience. We draw on rich qualitative data generated through creative methods, including film, photography and sketching, as part of object-elicitation interviews, focus groups, home tours and ‘pop-up stalls’. We develop three concepts regarding the function of moral things: manifesting, anchoring and conserving moral relations to describe how time, morality and the sensory are entwined.
    • 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)
      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 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)
      <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 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 unequal-time matter power spectrum: impact on weak lensing observables

      de la Bella, Lucia F.; email: lucia.fonsecadelabella@manchester.ac.uk; Tessore, Nicolas; email: n.tessore@ucl.ac.uk; Bridle, Sarah; email: sarah.bridle@manchester.ac.uk (IOP Publishing, 2021-08-02)
      Abstract: We investigate the impact of a common approximation of weak lensing power spectra: the use of single-epoch matter power spectra in integrals over redshift. We disentangle this from the closely connected Limber's approximation. We derive the unequal-time matter power spectrum at one-loop in standard perturbation theory and effective field theory to deal with non-linear physics. We compare these formalisms and conclude that the unequal-time power spectrum using effective field theory breaks for larger scales. As an alternative we introduce the midpoint approximation. We also provide, for the first time, a fitting function for the time evolution of the effective field theory counterterms based on the Quijote simulations. Then we compute the angular power spectrum using a range of approaches: the Limber approximation, and the geometric and midpoint approximations. We compare our results with the exact calculation at all angular scales using the unequal-time power spectrum. We use DES Y1 and LSST-like redshift distributions for our analysis. We find that the use of the Limber's approximation in weak lensing diverges from the exact calculation of the angular power spectrum on large-angle separations, ℓ < 10. Even though this deviation is of order 2% maximum for cosmic lensing, we find the biggest effect for galaxy clustering and galaxy-galaxy lensing. We show that not only is this true for upcoming galaxy surveys, but also for current data such as DES Y1. Finally, we make our pipeline and analysis publicly available as a Python package called unequalpy.