• Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

      Dave, Rajiv V.; orcid: 0000-0001-6827-8090; email: rajiv.dave@nhs.net; Kim, Baek; Courtney, Alona; O’Connell, Rachel; Rattay, Tim; Taxiarchi, Vicky P.; Kirkham, Jamie J.; Camacho, Elizabeth M.; Fairbrother, Patricia; Sharma, Nisha; et al. (Nature Publishing Group UK, 2021-03-25)
      Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown.
    • Breast Cancer Risk Assessment and Primary Prevention Advice in Primary Care: A Systematic Review of Provider Attitudes and Routine Behaviours

      Bellhouse, Sarah; orcid: 0000-0002-9549-1177; email: sarah.bellhouse@postgrad.manchester.ac.uk; Hawkes, Rhiannon E.; orcid: 0000-0003-0479-8163; email: rhiannon.hawkes@manchester.ac.uk; Howell, Sacha J.; email: sacha.howell@nhs.net; Gorman, Louise; email: louise.gorman@manchester.ac.uk; French, David P.; orcid: 0000-0002-7663-7804; email: david.french@manchester.ac.uk (MDPI, 2021-08-18)
      Implementing risk-stratified breast cancer screening is being considered internationally. It has been suggested that primary care will need to take a role in delivering this service, including risk assessment and provision of primary prevention advice. This systematic review aimed to assess the acceptability of these tasks to primary care providers. Five databases were searched up to July–August 2020, yielding 29 eligible studies, of which 27 were narratively synthesised. The review was pre-registered (PROSPERO: CRD42020197676). Primary care providers report frequently collecting breast cancer family history information, but rarely using quantitative tools integrating additional risk factors. Primary care providers reported high levels of discomfort and low confidence with respect to risk-reducing medications although very few reported doubts about the evidence base underpinning their use. Insufficient education/training and perceived discomfort conducting both tasks were notable barriers. Primary care providers are more likely to accept an increased role in breast cancer risk assessment than advising on risk-reducing medications. To realise the benefits of risk-based screening and prevention at a population level, primary care will need to proactively assess breast cancer risk and advise on risk-reducing medications. To facilitate this, adaptations to infrastructure such as integrated tools are necessary in addition to provision of education.
    • Brief Engagement and Acceptance Coaching for Hospice Settings (the BEACHeS study): results from a Phase I study of acceptability and initial effectiveness in people with non-curative cancer

      Hulbert-Williams, Nicholas J.; email: n.hulbertwilliams@chester.ac.uk; Norwood, Sabrina F.; Gillanders, David; Finucane, Anne M.; Spiller, Juliet; Strachan, Jenny; Millington, Susan; Kreft, Joseph; Swash, Brooke (BioMed Central, 2021-06-25)
      Abstract: Objectives: Transitioning into palliative care is psychologically demanding for people with advanced cancer, and there is a need for acceptable and effective interventions to support this. We aimed to develop and pilot test a brief Acceptance and Commitment Therapy (ACT) based intervention to improve quality of life and distress. Methods: Our mixed-method design included: (i) quantitative effectiveness testing using Single Case Experimental Design (SCED), (ii) qualitative interviews with participants, and (iii) focus groups with hospice staff. The five-session, in-person intervention was delivered to 10 participants; five completed at least 80%. Results: At baseline, participants reported poor quality of life but low distress. Most experienced substantial physical health deterioration during the study. SCED analysis methods did not show conclusively significant effects, but there was some indication that outcome improvement followed changes in expected intervention processes variables. Quantitative and qualitative data together demonstrates acceptability, perceived effectiveness and safety of the intervention. Qualitative interviews and focus groups were also used to gain feedback on intervention content and to make design recommendations to maximise success of later feasibility trials. Conclusions: This study adds to the growing evidence base for ACT in people with advanced cancer. A number of potential intervention mechanisms, for example a distress-buffering hypothesis, are raised by our data and these should be addressed in future research using randomised controlled trial designs. Our methodological recommendations—including recruiting non-cancer diagnoses, and earlier in the treatment trajectory—likely apply more broadly to the delivery of psychological intervention in the palliative care setting. This study was pre-registered on the Open Science Framework (Ref: 46,033) and retrospectively registered on the ISRCTN registry (Ref: ISRCTN12084782).
    • Brief intervention using the PaperWeight Armband to identify older people at risk of undernutrition in the community: a preliminary evaluation.

      Edwards, Steven; Farrer, Kirstine; Rose, Emma; Haynes, David; McLaughlin, John; orcid: 0000-0001-6158-5135; email: john.mclaughlin@manchester.ac.uk (2021-06-22)
      The risk of undernutrition in older adults in the community is high, with clear negative impacts on health and well-being. Nutritional screening is not routine and undernutrition often goes unrecognised. A community-level population public health intervention has the potential to target environments where the risk of undernutrition is highest. A programme has been established locally using the PaperWeight Armband as a simple nutritional screening tool in residents over 65 years, followed by supporting advice and community interventions. We undertook a nested pilot cohort evaluation within the wider programme to assess whether this could impact positively. Participants found to be at risk of undernutrition in the programme were recruited consecutively. Baseline weight and other descriptors including accommodation and frailty were recorded, and then again at 12 weeks. 83 participants were recruited from a wide variety of community settings, age range 65-99 years; 75% were women. Sixty-seven recruits were followed up for 12-week review. Of these, 54 (81%) had a positive outcome, recording either weight gain (66%) or no weight loss (15%) at 12 weeks. Benefit was seen in all living circumstances but was least evident in the frailest participants. The intervention is associated with positive outcomes, with reduction or stabilisation of nutritional risk in the majority of participants studied. The intervention can be delivered in a wide range of settings and does not require healthcare professions for the screening. Longer and larger studies are now required to study the health, well-being and socioeconomic impacts of the intervention in depth. [Abstract copyright: © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.]
    • Bright daytime light enhances circadian amplitude in a diurnal mammal.

      Bano-Otalora, Beatriz; orcid: 0000-0003-4694-9943; Martial, Franck; Harding, Court; Bechtold, David A; orcid: 0000-0001-8676-8704; Allen, Annette E; orcid: 0000-0003-0214-7076; Brown, Timothy M; Belle, Mino D C; orcid: 0000-0002-4917-957X; Lucas, Robert J; orcid: 0000-0002-1088-8029; email: robert.lucas@manchester.ac.uk (2021-06-01)
      Mammalian circadian rhythms are orchestrated by a master pacemaker in the hypothalamic suprachiasmatic nuclei (SCN), which receives information about the 24 h light-dark cycle from the retina. The accepted function of this light signal is to reset circadian phase in order to ensure appropriate synchronization with the celestial day. Here, we ask whether light also impacts another key property of the circadian oscillation, its amplitude. To this end, we measured circadian rhythms in behavioral activity, body temperature, and SCN electrophysiological activity in the diurnal murid rodent following stable entrainment to 12:12 light-dark cycles at four different daytime intensities (ranging from 18 to 1,900 lx melanopic equivalent daylight illuminance). showed strongly diurnal activity and body temperature rhythms in all conditions, but measures of rhythm robustness were positively correlated with daytime irradiance under both entrainment and subsequent free run. Whole-cell and extracellular recordings of electrophysiological activity in ex vivo SCN revealed substantial differences in electrophysiological activity between dim and bright light conditions. At lower daytime irradiance, daytime peaks in SCN spontaneous firing rate and membrane depolarization were substantially depressed, leading to an overall marked reduction in the amplitude of circadian rhythms in spontaneous activity. Our data reveal a previously unappreciated impact of daytime light intensity on SCN physiology and the amplitude of circadian rhythms and highlight the potential importance of daytime light exposure for circadian health. [Abstract copyright: Copyright © 2021 the Author(s). Published by PNAS.]
    • Bright daytime light enhances circadian amplitude in a diurnal mammal.

      Bano-Otalora, Beatriz; orcid: 0000-0003-4694-9943; Martial, Franck; Harding, Court; Bechtold, David A; orcid: 0000-0001-8676-8704; Allen, Annette E; orcid: 0000-0003-0214-7076; Brown, Timothy M; orcid: 0000-0002-5625-4750; Belle, Mino D C; orcid: 0000-0002-4917-957X; Lucas, Robert J; orcid: 0000-0002-1088-8029; email: robert.lucas@manchester.ac.uk (2021-06-01)
      Mammalian circadian rhythms are orchestrated by a master pacemaker in the hypothalamic suprachiasmatic nuclei (SCN), which receives information about the 24 h light-dark cycle from the retina. The accepted function of this light signal is to reset circadian phase in order to ensure appropriate synchronization with the celestial day. Here, we ask whether light also impacts another key property of the circadian oscillation, its amplitude. To this end, we measured circadian rhythms in behavioral activity, body temperature, and SCN electrophysiological activity in the diurnal murid rodent <i>Rhabdomys pumilio</i> following stable entrainment to 12:12 light-dark cycles at four different daytime intensities (ranging from 18 to 1,900 lx melanopic equivalent daylight illuminance). <i>R. pumilio</i> showed strongly diurnal activity and body temperature rhythms in all conditions, but measures of rhythm robustness were positively correlated with daytime irradiance under both entrainment and subsequent free run. Whole-cell and extracellular recordings of electrophysiological activity in ex vivo SCN revealed substantial differences in electrophysiological activity between dim and bright light conditions. At lower daytime irradiance, daytime peaks in SCN spontaneous firing rate and membrane depolarization were substantially depressed, leading to an overall marked reduction in the amplitude of circadian rhythms in spontaneous activity. Our data reveal a previously unappreciated impact of daytime light intensity on SCN physiology and the amplitude of circadian rhythms and highlight the potential importance of daytime light exposure for circadian health.
    • Bringing the doctoral thesis by published papers to the Social Sciences and the Humanities: A quantitative easing? A small study of doctoral thesis submission rules and practice in two disciplines in the UK

      Rigby, John; orcid: 0000-0001-9833-5965; email: John.Rigby@manchester.ac.uk; Jones, Barbara; orcid: 0000-0003-2717-6076 (Springer International Publishing, 2020-05-15)
      Abstract: This paper examines how an alternative to the traditional monograph form of the doctoral thesis is emerging that reflects a new approach to the valuation and designation of scientific outputs. This new approach, based on co-citation as underpinning principle for the measurement of knowledge structures, values knowledge and knowledge producers in increasingly quantitative terms. Such a change aligns with wider institutional market-based approaches that have been transforming higher education sectors world-wide. Under these influences, which prioritize quantification and tangibility of output, with quality equated with citation, the thesis, a key institution of the university, is now subject to pressures to transform and be constituted by a series of publishable papers, referred to by a variety of terms, the most common being ‘Thesis by Published Papers’, although ‘Journal Format Thesis’, ‘Alternative Format Thesis’, and ‘Integrated Thesis’ are also used. While the scientific disciplines have traditionally been closer to this paper-based model, albeit with significant national variations, Social Sciences and Humanities subjects are now being affected. We present evidence from a small study of the UK higher education sector of organisational regulations in 54 departments concerning doctoral degree submission formats in two disciplines in the Humanities and Social Sciences (History and Sociology). We investigate the prevalence of this new practice, investigate some of its key aspects, and identify a number of questions for future research on this emerging and important topic.
    • British prisoners of war in First World War Germany

      Grady, Tim (Informa UK Limited, 2020-05-29)
    • Broadband measurement of true transverse relaxation rates in systems with coupled protons: application to the study of conformational exchange.

      Kiraly, Peter; orcid: 0000-0003-3540-4876; Dal Poggetto, Guilherme; orcid: 0000-0003-0591-9166; Castañar, Laura; orcid: 0000-0002-4731-0626; Nilsson, Mathias; orcid: 0000-0003-3301-7899; Deák, Andrea; orcid: 0000-0001-7988-0255; Morris, Gareth A; orcid: 0000-0002-4859-6259 (2021-08-03)
      Accurate measurement of transverse relaxation rates in coupled spin systems is important in the study of molecular dynamics, but is severely complicated by the signal modulations caused by scalar couplings in spin echo experiments. The most widely used experiments for measuring transverse relaxation in coupled systems, CPMG and PROJECT, can suppress such modulations, but they also both suppress some relaxation contributions, and average relaxation rates between coupled spins. Here we introduce a new experiment which for the first time allows accurate broadband measurement of transverse relaxation rates of coupled protons, and hence the determination of exchange rate constants in slow exchange from relaxation measurements. The problems encountered with existing methods are illustrated, and the use of the new method is demonstrated for the classic case of hindered amide rotation and for the more challenging problem of exchange between helical enantiomers of a gold(i) complex. [Abstract copyright: This journal is © The Royal Society of Chemistry.]
    • Building a consistent parton shower

      Forshaw, Jeffrey R.; Holguin, Jack; orcid: 0000-0001-5183-2673; email: jack.holguin@manchester.ac.uk; Plätzer, Simon (Springer Berlin Heidelberg, 2020-09-01)
      Abstract: Modern parton showers are built using one of two models: dipole showers or angular ordered showers. Both have distinct strengths and weaknesses. Dipole showers correctly account for wide-angle, soft gluon emissions and track the leading flows in QCD colour charge but they are known to mishandle partonic recoil. Angular ordered showers keep better track of partonic recoil and correctly include large amounts of wide-angle, soft physics but azimuthal averaging means they are known to mishandle some correlations. In this paper, we derive both approaches from the same starting point; linking our under- standing of the two showers. This insight allows us to construct a new dipole shower that has all the strengths of a standard dipole shower together with the collinear evolution of an angular-ordered shower. We show that this new approach corrects the next-to-leading- log errors previously observed in parton showers and improves their sub-leading-colour accuracy.
    • Building Information Modelling Diffusion Research in Developing Countries: A User Meta-Model Approach

      Adekunle, Samuel Adeniyi; orcid: 0000-0002-9230-2924; email: sasamuel@uj.ac.za; Ejohwomu, Obuks; orcid: 0000-0001-7098-8999; email: obuks.ejohwomu@manchester.ac.uk; Aigbavboa, Clinton Ohis; email: caigbavboa@uj.ac.za (MDPI, 2021-06-22)
      Building information modelling (BIM) has become a common denominator for information management, efficiency, collaboration, and productivity in the construction industry. The adoption of building information modelling has been assessed to be unequal in the construction industry the world over. It has been observed that developing countries are struggling with BIM adoption and are at a beginner stage in the process. Meanwhile, there have been different research efforts focused on advancing BIM diffusion in developing countries. This study focused on reviewing the research trend and knowledge domains of BIM research in developing countries. The study analysed scholarly publications from selected developing countries sourced from the Scopus database from 2005 to 2019; the study covered BIM research efforts since their commencement in developing countries. The study identified the different research trends and the current focus through visualisations using VOS viewer software. The most influential and productive researchers were also identified. This research contributes to the extant body of knowledge by synthesizing the state of the art of BIM research in developing countries. Furthermore, it provides the pre-COVID-19 BIM diffusion status in developing countries.
    • Building the future of public policy in the Basque Country: Etorkizuna Eraikiz, a metagovernance approach

      Barandiaran, Xabier; Luna, Alvaro; orcid: 0000-0002-1372-1275; Bendall, Mark (Informa UK Limited, 2018-08-02)
    • Bulk and Confined Benzene-Cyclohexane Mixtures Studied by an Integrated Total Neutron Scattering and NMR Method

      Hughes, Terri-Louise; orcid: 0000-0002-6389-8669; email: terri-louise.hughes@manchester.ac.uk; Falkowska, Marta; orcid: 0000-0003-0888-005X; Leutzsch, Markus; orcid: 0000-0001-8171-9399; Sederman, Andrew J.; orcid: 0000-0002-7866-5550; Mantle, Mick D.; Headen, Thomas F.; orcid: 0000-0003-0095-5731; Youngs, Tristan G. A.; orcid: 0000-0003-3538-5572; Bowron, Daniel T.; orcid: 0000-0002-4557-1929; Hardacre, Christopher; orcid: 0000-0001-7256-6765 (Springer US, 2021-04-23)
      Abstract: Herein mixtures of cyclohexane and benzene have been investigated in both the bulk liquid phase and when confined in MCM-41 mesopores. The bulk mixtures have been studied using total neutron scattering (TNS), and the confined mixtures have been studied by a new flow-utilising, integrated TNS and NMR system (Flow NeuNMR), all systems have been analysed using empirical potential structure refinement (EPSR). The Flow NeuNMR setup provided precise time-resolved chemical sample composition through NMR, overcoming the difficulties of ensuring compositional consistency for computational simulation of data ordinarily found in TNS experiments of changing chemical composition—such as chemical reactions. Unique to the liquid mixtures, perpendicularly oriented benzene molecules have been found at short distances from the cyclohexane rings in the regions perpendicular to the carbon–carbon bonds. Upon confinement of the hydrocarbon mixtures, a stronger parallel orientational preference of unlike molecular dimers, at short distances, has been found. At longer first coordination shell distances, the like benzene molecular spatial organisation within the mixture has also found to be altered upon confinement.
    • Burden of illness of progressive familial intrahepatic cholestasis in the US, UK, France, and Germany: study rationale and protocol of the PICTURE study

      Ruiz-Casas, Leonardo; O’Hara, Sonia; orcid: 0000-0002-9119-8336; Mighiu, Claudia; Finnegan, Alan; Taylor, Alison; Ventura, Emily; Dhawan, Anil; Murray, Karen F; Schattenberg, Jorn; orcid: 0000-0002-4224-4703; Willemse, Jose; et al. (Informa UK Limited, 2021-01-07)
    • Burden of illness of progressive familial intrahepatic cholestasis in the US, UK, France, and Germany: study rationale and protocol of the PICTURE study

      Ruiz-Casas, Leonardo; O’Hara, Sonia; orcid: 0000-0002-9119-8336; Mighiu, Claudia; Finnegan, Alan; Taylor, Alison; Ventura, Emily; Dhawan, Anil; Murray, Karen F; Schattenberg, Jorn; orcid: 0000-0002-4224-4703; Willemse, Jose; et al. (Informa UK Limited, 2021-01-07)
    • Burden of illness of progressive familial intrahepatic cholestasis in the US, UK, France, and Germany: study rationale and protocol of the PICTURE study.

      Ruiz-Casas, Leonardo; O'Hara, Sonia; orcid: 0000-0002-9119-8336; Mighiu, Claudia; Finnegan, Alan; Taylor, Alison; Ventura, Emily; Dhawan, Anil; Murray, Karen F; Schattenberg, Jorn; orcid: 0000-0002-4224-4703; Willemse, Jose; et al. (2021-01-07)
      : Progressive familial intrahepatic cholestasis (PFIC) is an ultra-rare disease with a considerable burden on pediatric patients and their caregivers, impacting quality of life (QoL). The mortality rates highlight a significant need for efficacious treatments. Real-world data on associated costs and QoL are needed to gauge the potential impact of new pharmacological treatments. : Clinical and socio-economic burden of PFIC on patients/caregivers, health systems, and society will be assessed. Patient/caregiver- and physician-level retrospective cross-sectional data will be collected from the US, UK, France, and Germany, for PFIC types 1, 2, 3. A representative sample of physicians will provide clinical and resource utilization information using an electronic Case Report Form (eCRF). Patient/caregiver surveys will collect socio-economic and QoL data, enabling assessment of PFIC impact on QoL. Mean costs (direct medical/non-medical, indirect) will be calculated. The study materials were reviewed by medical professionals and patient representatives and received ethical approval from the University of Chester. : The study aims to reveal the unmet medical need, disease burden, resource utilization, and costs of PFIC, to raise awareness with policymakers and healthcare professionals, and provide support for the patient/caregiver community. As novel PFIC therapies recently emerged, this study will yield quantifiable data for health technology assessments.
    • 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 C-H arylation process is described using visible light. Using the readily available catalyst [RuCl ( -cymene)] , visible light irradiation was found to enable arylation of 2-aryl-pyridines at room temperature for a range of aryl bromides and iodides. [Abstract copyright: This journal is © The Royal Society of Chemistry.]
    • Ca

      Lim, Dmitry; email: dmitry.lim@uniupo.it; Dematteis, Giulia; Tapella, Laura; Genazzani, Armando A; Calì, Tito; Brini, Marisa; Verkhratsky, Alexei; email: alexej.verkhratsky@manchester.ac.uk (2021-08-05)
      Mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) are morpho-functional units, formed at the loci of close apposition of the ER-forming endomembrane and outer mitochondrial membrane (OMM). These sites contribute to fundamental cellular processes including lipid biosynthesis, autophagy, apoptosis, ER-stress and calcium (Ca ) signalling. At MERCS, Ca ions are transferred from the ER directly to mitochondria through a core protein complex composed of inositol-1,4,5 trisphosphate receptor (InsP R), voltage-gated anion channel 1 (VDAC1), mitochondrial calcium uniporter (MCU) and adaptor protein glucose-regulated protein 75 (Grp75); this complex is regulated by several associated proteins. Deregulation of ER-mitochondria Ca transfer contributes to pathogenesis of neurodegenerative and other diseases. The efficacy of Ca transfer between ER and mitochondria depends on the protein composition of MERCS, which controls ER-mitochondria interaction regulating, for example, the transversal distance between ER membrane and OMM and the extension of the longitudinal interface between ER and mitochondria. These parameters are altered in neurodegeneration. Here we overview the ER and mitochondrial Ca homeostasis, the composition of ER-mitochondrial Ca transfer machinery and alterations of the ER-mitochondria Ca transfer in three major neurodegenerative diseases: motor neurone diseases, Parkinson disease and Alzheimer's disease. [Abstract copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.]
    • Cage and maternal effects on the bacterial communities of the murine gut.

      Singh, Gurdeep; Brass, Andrew; Cruickshank, Sheena M; email: sheena.cruickshank@manchester.ac.uk; Knight, Christopher G (2021-05-10)
      Findings from gut microbiome studies are strongly influenced by both experimental and analytical factors that can unintentionally bias their interpretation. Environment is also critical. Both co-housing and maternal effects are expected to affect microbiomes and have the potential to confound other manipulated factors, such as genetics. We therefore analysed microbiome data from a mouse experiment using littermate controls and tested differences among genotypes (wildtype versus colitis prone-mdr1a ), gut niches (stool versus mucus), host ages (6 versus 18 weeks), social groups (co-housed siblings of different genotypes) and maternal influence. We constructed a 16S phylogenetic tree from bacterial communities, fitting random forest models using all 428,234 clades identified. Models discriminated all criteria except host genotype, where no community differences were found. Host social groups differed in abundant, low-level, taxa whereas intermediate phylogenetic and abundance scales distinguished ages and niches. Thus, a carefully controlled experiment treating evolutionary clades of microbes equivalently without reference to taxonomy, clearly identifies whether and how gut microbial communities are distinct across ecologically important factors (niche and host age) and other experimental factors, notably cage effects and maternal influence. These findings highlight the importance of considering such environmental factors in future microbiome studies.