• Proton-coupled electron transfer reactivities of electronically divergent heme superoxide intermediates: a kinetic, thermodynamic, and theoretical study.

      Mondal, Pritam; orcid: 0000-0002-7071-1970; Ishigami, Izumi; Gérard, Emilie F; Lim, Chaeeun; Yeh, Syun-Ru; de Visser, Sam P; orcid: 0000-0002-2620-8788; Wijeratne, Gayan B; orcid: 0000-0001-7609-6406 (2021-05-27)
      Heme superoxides are one of the most versatile metallo-intermediates in biology, and they mediate a vast variety of oxidation and oxygenation reactions involving O<sub>2(g)</sub>. Overall proton-coupled electron transfer (PCET) processes they facilitate may proceed <i>via</i> several different mechanistic pathways, attributes of which are not yet fully understood. Herein we present a detailed investigation into concerted PCET events of a series of geometrically similar, but electronically disparate synthetic heme superoxide mimics, where unprecedented, PCET feasibility-determining electronic effects of the heme center have been identified. These electronic factors firmly modulate both thermodynamic and kinetic parameters that are central to PCET, as supported by our experimental and theoretical observations. Consistently, the most electron-deficient superoxide adduct shows the strongest driving force for PCET, whereas the most electron-rich system remains unreactive. The pivotal role of these findings in understanding significant heme systems in biology, as well as in alternative energy applications is also discussed.
    • Psychiatric face of COVID-19

      Steardo, Luca, Jr.; orcid: 0000-0002-7077-3506; email: steardo@unicz.it; Steardo, Luca; orcid: 0000-0003-3570-2195; email: luca.steardo@uniroma1.it; Verkhratsky, Alexei; orcid: 0000-0003-2592-9898; email: alexej.verkhratsky@manchester.ac.uk (Nature Publishing Group UK, 2020-07-30)
      Abstract: The Coronavirus Disease 2019 (COVID-19) represents a severe multiorgan pathology which, besides cardio-respiratory manifestations, affects the function of the central nervous system (CNS). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similarly to other coronaviruses demonstrate neurotropism; the viral infection of the brain stem may complicate the course of the disease through damaging central cardio-respiratory control. The systemic inflammation as well as neuroinflammatory changes are associated with massive increase of the brain pro-inflammatory molecules, neuroglial reactivity, altered neurochemical landscape and pathological remodelling of neuronal networks. These organic changes, emerging in concert with environmental stress caused by experiences of intensive therapy wards, pandemic fears and social restrictions, promote neuropsychiatric pathologies including major depressive disorder, bipolar disorder (BD), various psychoses, obsessive-compulsive disorder and post-traumatic stress disorder. The neuropsychiatric sequelae of COVID-19 represent serious clinical challenge that has to be considered for future complex therapies.
    • Psychometric Validation of the Psoriasis Symptoms and Impacts Measure (P-SIM), a Novel Patient-Reported Outcome Instrument for Patients with Plaque Psoriasis, Using Data from the BE VIVID and BE READY Phase 3 Trials

      Warren, Richard B.; email: Richard.Warren@manchester.ac.uk; Gottlieb, Alice B.; Merola, Joseph F.; Garcia, Llenalia; Cioffi, Christopher; Peterson, Luke; Pelligra, Christopher; Ciaravino, Valerie (Springer Healthcare, 2021-07-14)
      Abstract: Introduction: Plaque psoriasis can significantly impact patients’ quality of life. We assessed psychometric properties of the Psoriasis Symptoms and Impacts Measure (P-SIM), developed to capture patients’ experiences of signs, symptoms and impacts of psoriasis. Methods: Pooled, blinded, 16-week data from 1002 patients in the BE VIVID and BE READY bimekizumab phase 3 trials were analysed. The suitability of the P-SIM missing score rule (weekly scores considered missing if ≥ 4 daily scores were missing) was assessed. Test–retest reliability was evaluated using intraclass correlation coefficients (ICCs). Convergent validity was assessed between P-SIM and relevant patient-reported outcome (PRO) (Dermatology Life Quality Index [DLQI], DLQI item 1 [skin symptoms], Patient Global Assessment of Psoriasis) and clinician-reported outcome (ClinRO) scores (Psoriasis Area and Severity Index [PASI], Investigator’s Global Assessment [IGA]) at baseline and week 16. Known-groups validity was assessed, comparing P-SIM scores between patient subgroups predefined using PASI/IGA scores. Sensitivity to change over 16 weeks was evaluated; responder definition (RD) thresholds were explored. Results: The missing score rule used did not impact P-SIM scores. Test–retest reliability analyses demonstrated excellent score reproducibility (ICC 0.91–0.98). Inter-item correlations at baseline and week 16 were strong (> 0.5), apart from “choice of clothing” with “skin pain” and “burning” at baseline (both 0.49). All P-SIM scores were moderately to strongly correlated with other outcomes, demonstrating convergent validity, apart from ClinROs (PASI, IGA) at baseline that had low variability. P-SIM scores discriminated known groups at week 16, confirming known-groups validity. Changes from baseline to week 16 in P-SIM and other clinically relevant outcomes were strongly correlated (> 0.5; weaker with ClinROs), establishing sensitivity to change. Anchor-based RD analyses determined a four-point P-SIM item score decrease as indicative of marked clinically meaningful improvement. Conclusion: P-SIM scores demonstrated good reliability, validity and sensitivity to change. A four-point RD threshold could be used to assess 16-week treatment effects. Trial Registration: BE VIVID: NCT03370133; BE READY: NCT03410992.
    • Psychometric Validation of the Psoriasis Symptoms and Impacts Measure (P-SIM), a Novel Patient-Reported Outcome Instrument for Patients with Plaque Psoriasis, Using Data from the BE VIVID and BE READY Phase 3 Trials.

      Warren, Richard B; email: richard.warren@manchester.ac.uk; Gottlieb, Alice B; Merola, Joseph F; Garcia, Llenalia; Cioffi, Christopher; Peterson, Luke; Pelligra, Christopher; Ciaravino, Valerie (2021-07-14)
      Plaque psoriasis can significantly impact patients' quality of life. We assessed psychometric properties of the Psoriasis Symptoms and Impacts Measure (P-SIM), developed to capture patients' experiences of signs, symptoms and impacts of psoriasis. Pooled, blinded, 16-week data from 1002 patients in the BE VIVID and BE READY bimekizumab phase 3 trials were analysed. The suitability of the P-SIM missing score rule (weekly scores considered missing if ≥ 4 daily scores were missing) was assessed. Test-retest reliability was evaluated using intraclass correlation coefficients (ICCs). Convergent validity was assessed between P-SIM and relevant patient-reported outcome (PRO) (Dermatology Life Quality Index [DLQI], DLQI item 1 [skin symptoms], Patient Global Assessment of Psoriasis) and clinician-reported outcome (ClinRO) scores (Psoriasis Area and Severity Index [PASI], Investigator's Global Assessment [IGA]) at baseline and week 16. Known-groups validity was assessed, comparing P-SIM scores between patient subgroups predefined using PASI/IGA scores. Sensitivity to change over 16 weeks was evaluated; responder definition (RD) thresholds were explored. The missing score rule used did not impact P-SIM scores. Test-retest reliability analyses demonstrated excellent score reproducibility (ICC 0.91-0.98). Inter-item correlations at baseline and week 16 were strong (> 0.5), apart from "choice of clothing" with "skin pain" and "burning" at baseline (both 0.49). All P-SIM scores were moderately to strongly correlated with other outcomes, demonstrating convergent validity, apart from ClinROs (PASI, IGA) at baseline that had low variability. P-SIM scores discriminated known groups at week 16, confirming known-groups validity. Changes from baseline to week 16 in P-SIM and other clinically relevant outcomes were strongly correlated (> 0.5; weaker with ClinROs), establishing sensitivity to change. Anchor-based RD analyses determined a four-point P-SIM item score decrease as indicative of marked clinically meaningful improvement. P-SIM scores demonstrated good reliability, validity and sensitivity to change. A four-point RD threshold could be used to assess 16-week treatment effects. BE VIVID: NCT03370133; BE READY: NCT03410992. [Abstract copyright: © 2021. The Author(s).]
    • Psychosocial stress has weaker than expected effects on episodic memory and related cognitive abilities: a meta-analysis.

      McManus, Elizabeth; Talmi, Deborah; Haroon, Hamied; Muhlert, Nils; email: nils.muhlert@manchester.ac.uk (2021-11-05)
      The impact of stress on episodic memory and related cognitive abilities is well documented in both animal and human literature. However, it is unclear whether the same cognitive effects result from all forms of stress - in particular psychosocial stress. This review systematically explored the effects of psychosocial stress on episodic memory and associated cognitive abilities. PubMed, PsycInfo, and Web of Science databases were searched. Fifty-one studies were identified and compared based on the timing of stress induction. A small positive effect of post-learning psychosocial stress with a long retention interval was shown. No other effects of psychosocial stress were seen. Re-analysis of previous meta-analyses also showed no significant effect of psychosocial stress on episodic memory, highlighting potentially different effects between stressor types. Psychosocial stress also had a moderately different effect when emotional vs. neutral stimuli were compared. Finally, psychosocial stress also decreased performance on executive function, but not working memory tasks. Our findings demonstrate that psychosocial stress may not have the clear effects on episodic memory previously ascribed to it. [Abstract copyright: Copyright © 2021. Published by Elsevier Ltd.]
    • Public affairs in a time of coronavirus.

      Moss, Danny; harris, Phil (2020-08-10)
    • Public Health Scotland - the first year: successes and lessons.

      Phin, Nick; email: nicholas.phin@phs.scot (2021-06)
      Over its first year Public Health Scotland (PHS) played a key role in the national vaccination programme by providing professional leadership and expertise. We expedited the reporting of all aspects of the pandemic, and accelerated rapid evidence reviews. We contributed to rigorous research showing that: vaccination reduced hospitalisation by 90%, and the transmission of COVID-19 within households by 55%; hence vaccination works. Lessons for the future included strengthening whole genome sequencing to manage COVID-19 and to prepare for future pathogens. COVID-19 also stimulated the redesign of many health and social care services: by exploiting digital media; by implementing evidence on reducing barriers to service delivery; and by greater integration - of projects rather than organisations - enabling groups who had not worked together to address common issues. PHS and partners soon recognised the need to mitigate the adverse impact of the pandemic on existing inequalities. So we aim to 'build back fairer' as the pandemic recedes, by pursuing PHS's four priorities: poverty; children and young people; place and community; and mental health and well-being.
    • Public preferences regarding data linkage for research: a discrete choice experiment comparing Scotland and Sweden

      Tully, Mary P.; orcid: 0000-0003-2100-3983; email: mary.p.tully@manchester.ac.uk; Bernsten, Cecilia; Aitken, Mhairi; Vass, Caroline (BioMed Central, 2020-06-16)
      Abstract: Background: There are increasing examples of linking data on healthcare resource use and patient outcomes from different sectors of health and social care systems. Linked data are generally anonymised, meaning in most jurisdictions there are no legal restrictions to their use in research conducted by public or private organisations. Secondary use of anonymised linked data is contentious in some jurisdictions but other jurisdictions are known for their use of linked data. The publics’ perceptions of the acceptability of using linked data is likely to depend on a number of factors. This study aimed to quantify the preferences of the public to understand the factors that affected views about types of linked data and its use in two jurisdictions. Method: An online discrete choice experiment (DCE) previously conducted in Scotland was adapted and replicated in Sweden. The DCE was designed, comprising five attributes, to elicit the preferences from a representative sample of the public in both jurisdictions. The five attributes (number of levels) were: type of researcher using linked data (four); type of data being linked (four); purpose of the research (three); use of profit from using linked data (four); who oversees the research (four). Each DCE contained 6 choice-sets asking respondents to select their preferred option from two scenarios or state neither were acceptable. Background questions included socio-demographics. DCE data were analysed using conditional and heteroskedastic conditional logit models to create forecasts of acceptability. Results: The study sample comprised members of the public living in Scotland (n = 1004) and Sweden (n = 974). All five attributes were important in driving respondents’ choices. Swedish and Scottish preferences were mostly homogenous with the exception of ‘who oversees the research using linked data’, which had relatively less impact on the choices observed from Scotland. For a defined ‘typical’ linked data scenario, the probability (on average) of acceptance was 85.7% in Sweden and 82.4% in Scotland. Conclusion: This study suggests that the public living in Scotland and Sweden are open to using anonymised linked data in certain scenarios for research purposes but some caution is advisable if the anonymised linked data joins health to non-health data.
    • Publication outperformance among global South researchers: An analysis of individual-level and publication-level predictors of positive deviance

      Albanna, Basma; orcid: 0000-0002-6884-1610; email: basma.albanna@manchester.ac.uk; Handl, Julia; Heeks, Richard (Springer International Publishing, 2021-09-13)
      Abstract: Research and development are central to economic growth, and a key challenge for countries of the global South is that their research performance lags behind that of the global North. Yet, among Southern researchers, a few significantly outperform their peers and can be styled research “positive deviants” (PDs). In this paper we ask: who are those PDs, what are their characteristics and how are they able to overcome some of the challenges facing researchers in the global South? We examined a sample of 203 information systems researchers in Egypt who were classified into PDs and non-PDs (NPDs) through an analysis of their publication and citation data. Based on six citation metrics, we were able to identify and group 26 PDs. We then analysed their attributes, attitudes, practices, and publications using a mixed-methods approach involving interviews, a survey and analysis of publication-related datasets. Two predictive models were developed using partial least squares regression; the first predicted if a researcher is a PD or not using individual-level predictors and the second predicted if a paper is a paper of a PD or not using publication-level predictors. PDs represented 13% of the researchers but produced about half of all publications, and had almost double the citations of the overall NPD group. At the individual level, there were significant differences between both groups with regard to research collaborations, capacity development, and research directions. At the publication level, there were differences relating to the topics pursued, publication outlets targeted, and paper features such as length of abstract and number of authors.
    • Publisher Correction: 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. (2021-06-23)
    • Publisher Correction: 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. (2021-06-23)
    • Publisher Correction: 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, 2021-06-23)
    • Publisher Correction: Control of electron–electron interaction in graphene by proximity screening

      Kim, M.; orcid: 0000-0001-6304-6901; Xu, S. G.; orcid: 0000-0002-0589-5291; Berdyugin, A. I.; Principi, A.; Slizovskiy, S.; Xin, N.; Kumaravadivel, P.; orcid: 0000-0002-9817-1697; Kuang, W.; orcid: 0000-0003-4309-365X; Hamer, M.; Kumar, R. Krishna; et al. (Nature Publishing Group UK, 2020-06-11)
      An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    • Publisher Correction: Methylation deficiency disrupts biological rhythms from bacteria to humans

      Fustin, Jean-Michel; orcid: 0000-0002-6200-6075; email: jean-michel.fustin@manchester.ac.uk; Ye, Shiqi; Rakers, Christin; orcid: 0000-0002-5668-6844; Kaneko, Kensuke; Fukumoto, Kazuki; Yamano, Mayu; Versteven, Marijke; Grünewald, Ellen; Cargill, Samantha J.; Tamai, T. Katherine; orcid: 0000-0002-5538-5206; et al. (Nature Publishing Group UK, 2020-06-04)
      An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    • Publisher Correction: The blue hue of einsteinium.

      Natrajan, Louise S; orcid: 0000-0002-9451-3557; email: louise.natrajan@manchester.ac.uk; Faulkner, Stephen; email: stephen.faulkner@keble.ox.ac.uk (2021-06-08)
    • Purification of Propylene and Ethylene by a Robust Metal–Organic Framework Mediated by Host–Guest Interactions

      Li, Jiangnan; Han, Xue; Kang, Xinchen; Chen, Yinlin; Xu, Shaojun; Smith, Gemma L.; Tillotson, Evan; Cheng, Yongqiang; McCormick McPherson, Laura J.; Teat, Simon J.; et al. (2021-06-07)
      Abstract: Industrial purification of propylene and ethylene requires cryogenic distillation and selective hydrogenation over palladium catalysts to remove propane, ethane and/or trace amounts of acetylene. Here, we report the excellent separation of equimolar mixtures of propylene/propane and ethylene/ethane, and of a 1/100 mixture of acetylene/ethylene by a highly robust microporous material, MFM‐520, under dynamic conditions. In situ synchrotron single crystal X‐ray diffraction, inelastic neutron scattering and analysis of adsorption thermodynamic parameters reveal that a series of synergistic host–guest interactions involving hydrogen bonding and π⋅⋅⋅π stacking interactions underpin the cooperative binding of alkenes within the pore. Notably, the optimal pore geometry of the material enables selective accommodation of acetylene. The practical potential of this porous material has been demonstrated by fabricating mixed‐matrix membranes comprising MFM‐520, Matrimid and PIM‐1, and these exhibit not only a high permeability for propylene (≈1984 Barrer), but also a separation factor of 7.8 for an equimolar mixture of propylene/propane at 298 K.
    • Purification of Propylene and Ethylene by a Robust Metal–Organic Framework Mediated by Host–Guest Interactions

      Li, Jiangnan; Han, Xue; Kang, Xinchen; Chen, Yinlin; Xu, Shaojun; Smith, Gemma L.; Tillotson, Evan; Cheng, Yongqiang; McCormick McPherson, Laura J.; Teat, Simon J.; et al. (2021-06-07)
      Abstract: Industrial purification of propylene and ethylene requires cryogenic distillation and selective hydrogenation over palladium catalysts to remove propane, ethane and/or trace amounts of acetylene. Here, we report the excellent separation of equimolar mixtures of propylene/propane and ethylene/ethane, and of a 1/100 mixture of acetylene/ethylene by a highly robust microporous material, MFM‐520, under dynamic conditions. In situ synchrotron single crystal X‐ray diffraction, inelastic neutron scattering and analysis of adsorption thermodynamic parameters reveal that a series of synergistic host–guest interactions involving hydrogen bonding and π⋅⋅⋅π stacking interactions underpin the cooperative binding of alkenes within the pore. Notably, the optimal pore geometry of the material enables selective accommodation of acetylene. The practical potential of this porous material has been demonstrated by fabricating mixed‐matrix membranes comprising MFM‐520, Matrimid and PIM‐1, and these exhibit not only a high permeability for propylene (≈1984 Barrer), but also a separation factor of 7.8 for an equimolar mixture of propylene/propane at 298 K.
    • A qualitative study exploring midlife women’s stages of change from domestic violence towards freedom

      Keeling, June J.; Smith, Debra; Fisher, Colleen; University of Chester; University of Central Lancashire; The University of Western Australia (BioMed Central, 2016-03-08)
      Background Domestic Violence (DV) remains a significant global health problem for women in contemporary society. Existing literature on midlife women’s experiences of domestic violence is limited and focuses on health implications. Leaving a violent relationship is a dynamic process that often requires multiple attempts and separations prior to final termination. The aim of this study was to explore the process of leaving a violent relationship for midlife women. Methods This qualitative study involved fifteen women aged between 40–55 who had accessed residential and non-residential community support services for domestic violence within the UK. Community-based support agencies provided these women with access to letters of invitation and participant information sheet explaining the study. The women notified agency staff who contacted the research team to arrange a mutually convenient time to meet within a safe place for both the women and researchers. It was stressed to all potential participants that no identifiable information would be shared with the agency staff. Women were considered survivors of DV if they defined themselves as such. Data were gathered through semi structured interviews, transcribed verbatim and thematically analysed. Results Midlife women appear to differ from younger women by transitioning quickly though the stages of change, moving rapidly through the breaking free onto the maintenance stage. This rapid transition is the resultant effect of living with long-term violence causing a shift in the women’s perception towards the violent partner, with an associated reclamation of power from within the violent relationship. A realisation that rapid departure from the violence may be critical in terms of personal safety, and the realisation that there was something ‘wrong’ within the relationship, a ‘day of dawning’ that had not been apparent previously appears to positively affect the trajectory of leaving. Conclusions Midlife women appeared to navigate through the stages of change in a rapid linear process, forging ahead and exiting the relationship with certainty and without considering options. Whilst these findings appear to differ from younger women’s process of leaving, further research is needed to explore and understand the optimum time for intervention and support to maximise midlife women’s opportunities to escape an abusive partner, before being reflected appropriately in policy and practice.