• Palladium catalysed C-H arylation of pyrenes: access to a new class of exfoliating agents for water-based graphene dispersions.

      Just-Baringo, Xavier; orcid: 0000-0003-2182-5960; Shin, Yuyoung; orcid: 0000-0003-4359-5406; Panigrahi, Adyasha; Zarattini, Marco; Nagyte, Vaiva; orcid: 0000-0003-0835-6039; Zhao, Ling; Kostarelos, Kostas; orcid: 0000-0002-2224-6672; Casiraghi, Cinzia; orcid: 0000-0001-7185-0377; Larrosa, Igor; orcid: 0000-0002-5391-7424 (2020-01-28)
      A new and diverse family of pyrene derivatives was synthesised <i>via</i> palladium-catalysed C-H <i>ortho</i>-arylation of pyrene-1-carboxylic acid. The strategy affords easy access to a broad scope of 2-substituted and 1,2-disubstituted pyrenes. The C1-substituent can be easily transformed into carboxylic acid, iodide, alkynyl, aryl or alkyl functionalities. This approach gives access to arylated pyrene ammonium salts, which outperformed their non-arylated parent compound during aqueous Liquid Phase Exfoliation (LPE) of graphite and compare favourably to state-of-the-art sodium pyrene-1-sulfonate <b>PS1</b>. This allowed the production of concentrated and stable suspensions of graphene flakes in water.
    • Palladium-doped hierarchical ZSM-5 for catalytic selective oxidation of allylic and benzylic alcohols

      Ding, Shengzhe; orcid: 0000-0003-2822-3882; Ganesh, Muhammad; Jiao, Yilai; Ou, Xiaoxia; Isaacs, Mark A.; orcid: 0000-0002-0335-4272; S'ari, Mark; Torres Lopez, Antonio; orcid: 0000-0001-7378-1811; Fan, Xiaolei; orcid: 0000-0002-9039-6736; email: xiaolei.fan@manchester.ac.uk; Parlett, Christopher M. A.; orcid: 0000-0002-3651-7314; email: christopher.parlett@manchester.ac.uk (The Royal Society, 2021-10-20)
      Hierarchical zeolites have the potential to provide a breakthrough in transport limitation, which hinders pristine microporous zeolites and thus may broaden their range of applications. We have explored the use of Pd-doped hierarchical ZSM-5 zeolites for aerobic selective oxidation (selox) of cinnamyl alcohol and benzyl alcohol to their corresponding aldehydes. Hierarchical ZSM-5 with differing acidity (H-form and Na-form) were employed and compared with two microporous ZSM-5 equivalents. Characterization of the four catalysts by X-ray diffraction, nitrogen porosimetry, NH3 temperature-programmed desorption, CO chemisorption, high-resolution scanning transmission electron microscopy, X-ray photoelectron spectroscopy and X-ray absorption spectroscopy allowed investigation of their porosity, acidity, as well as Pd active sites. The incorporation of complementary mesoporosity, within the hierarchical zeolites, enhances both active site dispersion and PdO active site generation. Likewise, alcohol conversion was also improved with the presence of secondary mesoporosity, while strong Brønsted acidity, present solely within the H-form systems, negatively impacted overall selectivity through undesirable self-etherification. Therefore, tuning support porosity and acidity alongside active site dispersion is paramount for optimal aldehyde production.
    • Pandemic Drones

      Hildebrand, Julia M.; email: hildebjm@eckerd.edu; Sodero, Stephanie; email: stephanie.sodero@manchester.ac.uk (Berghahn Books, 2021-03-01)
      When the novel coronavirus moved around the planet in early 2020, reconfiguring, slowing down, or halting everyday mobilities, another transport mode was mobilized: the pandemic drone. We highlight the increasing prominence of this aerial device by surveying international media coverage of pandemic drone use in the spring of 2020. To address a range of pandemic drone affordances and applications, we organize manifold cases under two broad categories: sensing and moving with the pandemic drone. Here we ask: what roles do, and could, drones play during the pandemic? Following the empirical examples and related mobilities research, we theorize the drone versus virus and the drone as virus. As such, the work identifies avenues for mobilities research into pandemic drones as a growing mobility domain. Moreover, in thinking through the pandemic drone, we demonstrate creative extensions of mobilities thinking that bridge biological and technological, as well as media and mobility frameworks when multiple public health and safety crises unfolded and intersected.
    • Panel Adjustment and Error Analysis for a Large Active Main Reflector Antenna by Using the Panel Adjustment Matrix

      Lian, Peiyuan; Wang, Congsi; Xue, Song; Xu, Qian; Wang, Na; Xiang, Binbin; Shi, Yu; Jia, Yu (Institute of Electrical and Electronics Engineers (IEEE), 2021)
    • Parental Licensing as Harm Reduction

      Shields, Liam; orcid: 0000-0001-9272-1937; email: liam.shields@manchester.ac.uk (Springer US, 2020-10-17)
      Abstract: In this paper, I will argue that some prominent objections to parental licensing rely on dubious claims about the existence of a very stringent, if not indefeasible, right to parent, which would be violated by licensing. I claim that attaching such stringency to the right only makes sense if we make a number of idealising assumptions. Otherwise, it is deeply implausible. Instead, I argue that we should evaluate parental licensing policies in much the same way we would harm reduction policies. By adopting this critical perspective, we can see that there are powerful, but quite different, reasons to be cautious about parental licensing relating to our ability to minimize the harmful effects of mass-parenting in a world of minimal surveillance and intervention.
    • Pathogenic Intronic Splice-Affecting Variants in MYBPC3 in Three Patients with Hypertrophic Cardiomyopathy

      Wood, Katherine A.; orcid: 0000-0002-6459-2127; email: katherine.wood@manchester.ac.uk; Ellingford, Jamie M.; email: jamie.ellingford@manchester.ac.uk; Eden, James; email: james.eden@mft.nhs.uk; Thomas, Huw B.; orcid: 0000-0001-9626-9706; email: huw.thomas@manchester.ac.uk; O’Keefe, Raymond T.; email: rokeefe@manchester.ac.uk; Hopton, Claire; email: claire.hopton@manchester.ac.uk; Newman, William G.; email: william.newman@manchester.ac.uk (MDPI, 2021-06-02)
      Genetic variants in MYBPC3 are one of the most common causes of hypertrophic cardiomyopathy (HCM). While variants in MYBPC3 affecting canonical splice site dinucleotides are a well-characterised cause of HCM, only recently has work begun to investigate the pathogenicity of more deeply intronic variants. Here, we present three patients with HCM and intronic splice-affecting MYBPC3 variants and analyse the impact of variants on splicing using in vitro minigene assays. We show that the three variants, a novel c.927-8G>A variant and the previously reported c.1624+4A>T and c.3815-10T>G variants, result in MYBPC3 splicing errors. Analysis of blood-derived patient RNA for the c.3815-10T>G variant revealed only wild type spliced product, indicating that mis-spliced transcripts from the mutant allele are degraded. These data indicate that the c.927-8G>A variant of uncertain significance and likely benign c.3815-10T>G should be reclassified as likely pathogenic. Furthermore, we find shortcomings in commonly applied bioinformatics strategies to prioritise variants impacting MYBPC3 splicing and re-emphasise the need for functional assessment of variants of uncertain significance in diagnostic testing.
    • Pathogenic noncoding variants in the neurofibromatosis and schwannomatosis predisposition genes

      Perez‐Becerril, Cristina; orcid: 0000-0003-1630-1943; Evans, D. Gareth; orcid: 0000-0002-8482-5784; Smith, Miriam J.; orcid: 0000-0002-3184-0817; email: miriam.smith@manchester.ac.uk (2021-07-29)
      Abstract: Neurofibromatosis type 1 (NF1), type 2 (NF2), and schwannomatosis are a group of autosomal dominant disorders that predispose to the development of nerve sheath tumors. Pathogenic variants (PVs) that cause NF1 and NF2 are located in the NF1 and NF2 loci, respectively. To date, most variants associated with schwannomatosis have been identified in the SMARCB1 and LZTR1 genes, and a missense variant in the DGCR8 gene was recently reported to predispose to schwannomas. In spite of the high detection rate for PVs in NF1 and NF2 (over 90% of non‐mosaic germline variants can be identified by routine genetic screening) underlying PVs for a proportion of clinical cases remain undetected. A higher proportion of non‐NF2 schwannomatosis cases have no detected PV, with PVs currently only identified in around 70%–86% of familial cases and 30%–40% of non‐NF2 sporadic schwannomatosis cases. A number of variants of uncertain significance have been observed for each disorder, many of them located in noncoding, regulatory, or intergenic regions. Here we summarize noncoding variants in this group of genes and discuss their established or potential role in the pathogenesis of NF1, NF2, and schwannomatosis.
    • Patient engagement in melanoma research: from bench to bedside

      Tivey, Ann; Huddar, Prerana; Shotton, Rohan; Cheese, Imogen; Daniels, Susanna; Lorigan, Paul; orcid: 0000-0002-8875-2164; J Lee, Rebecca; orcid: 0000-0003-2540-2009; email: Rebecca.lee-3@manchester.ac.uk (Future Medicine Ltd, 2021-07-02)
      Advances in research have transformed the management of melanoma in the past decade. In parallel, patient advocacy has gained traction, and funders are increasingly prioritizing patient and public involvement. Here we discuss the ways in which patients and the public can be engaged in different stages of the research process, from developing, prioritizing and refining the research question to preclinical studies and clinical trials, then finally to ongoing research in the clinic. We discuss the challenges and opportunities that exist at each stage in order to ensure that a representative population of patients and the public contribute to melanoma research both now and in the future.
    • Patient engagement in melanoma research: from bench to bedside

      Tivey, Ann; Huddar, Prerana; Shotton, Rohan; Cheese, Imogen; Daniels, Susanna; Lorigan, Paul; orcid: 0000-0002-8875-2164; J Lee, Rebecca; orcid: 0000-0003-2540-2009; email: Rebecca.lee-3@manchester.ac.uk (Future Medicine Ltd, 2021-07-02)
      Advances in research have transformed the management of melanoma in the past decade. In parallel, patient advocacy has gained traction, and funders are increasingly prioritizing patient and public involvement. Here we discuss the ways in which patients and the public can be engaged in different stages of the research process, from developing, prioritizing and refining the research question to preclinical studies and clinical trials, then finally to ongoing research in the clinic. We discuss the challenges and opportunities that exist at each stage in order to ensure that a representative population of patients and the public contribute to melanoma research both now and in the future.
    • Patient insights on living with idiopathic inflammatory myopathy and the limitations of disease activity measurement methods – a qualitative study

      Oldroyd, Alexander; orcid: 0000-0001-5701-6490; email: alexander.oldroyd@manchester.ac.uk; Dixon, William; Chinoy, Hector; Howells, Kelly (BioMed Central, 2020-09-21)
      Abstract: Background: The idiopathic inflammatory myopathies (IIMs) are chronic autoimmune conditions, typically resulting in proximal muscle weakness and impacting upon quality of life. Accurate measurement of IIM disease activity is imperative for appropriate medical management and carrying out valid clinical trials. The International Myositis Assessment and Clinical Studies Group (IMACS) “Disease Activity Core Set Measures” are the current gold-standard of IIM disease activity assessment. Anecdotally, patients with an IIM report that the IMACS Core Set Measures and other available methods do not necessarily capture their perceived disease activity. Investigating the patient experiences of living with an IIM and their views on the accuracy of the IMACS Core Set Measures will provide valuable insights for both clinical and research purposes. Methods: Eighteen interviews with patients with an IIM were carried out and analysed thematically, using a grounded theory approach. Experiences on living with an IIM and perceptions on the accuracy of disease activity measurement methods were explored. Results: Interview analysis revealed four themes: 1) fatigue, 2) pain, 3) day-to-day symptom variation, 4) limitations of creatine kinase levels and manual muscle testing. Conclusions: This study has provided valuable insights into patient experiences of living with an IIM. Aspects of IIM disease activity perceived not to be wholly measured by the IMACS Core Set Measures have also been identified. These findings have implications for future IIM clinical care and research, in particular providing justification for research into pain, fatigue and symptom variation.
    • Patient preferences and priorities for haemophilia gene therapy in the US: A discrete choice experiment

      Witkop, Michelle; Morgan, George; orcid: 0000-0003-2014-3415; email: george.morgan@hcdeconomics.com; O'Hara, Jamie; Recht, Michael; Buckner, Tyler W.; Nugent, Diane; Curtis, Randall; orcid: 0000-0002-6859-6432; O'Mahony, Brian; orcid: 0000-0001-9780-6972; Skinner, Mark W.; orcid: 0000-0002-0934-0680; Mulhern, Brendan; et al. (2021-07-26)
      Abstract: Introduction: Gene therapy has shown promise in clinical trials for patients with haemophilia, but patient preference studies have focused on factor replacement treatments. Aim: We conducted a discrete choice experiment (DCE) to investigate the relative importance and differential preferences patients provide for gene therapy attributes. Methods: We surveyed male adults with haemophilia in the United States recruited from patient panels including the National Hemophilia Foundation Community Voices in Research platform using an online survey over 4 months in 2020/21. Participants indicated preferences for gene therapy attributes including dosing frequency/durability, effect on annual bleeding, uncertainty related to side effects, impact on daily activities, impact on mental health, and post‐treatment requirements. The relative importance of each attribute was analysed overall and for subgroups based on haemophilia type and severity. Results: A total of 183 males with haemophilia A (n = 120) or B (n = 63) were included. Half (47%) had severe haemophilia; most (75%) were White. Overall, participants gave effect on bleeding rate the greatest relative importance (31%), followed by dose frequency/durability (26%), uncertainty regarding safety issues (17%), and impact on daily activities (11%). Dose frequency/durability had the greatest importance for those with haemophilia B (35%). Conclusion: People with haemophilia prioritised reduced bleeding and treatment burden; the former was more important in haemophilia A and the latter in haemophilia B, followed by safety and impact on daily life in this DCE of gene therapy attributes. These findings and differences can inform clinical and health policy decisions to improve health equity for people with haemophilia.
    • Patient preferences for stratified medicine in psoriasis: a discrete choice experiment

      Dalal, G.; orcid: 0000-0002-4073-4215; Wright, S.J.; Vass, C.M.; Davison, N.J.; Vander Stichele, G.; Smith, C.H.; Griffiths, C.E.M.; orcid: 0000-0001-5371-4427; Payne, K.; orcid: 0000-0002-3938-4350; email: katherine.payne@manchester.ac.uk; the PSORT Consortium (2021-07-29)
      Summary: Background: New technologies have enabled the potential for stratified medicine in psoriasis. It is important to understand patients’ preferences to enable the informed introduction of stratified medicine, which is likely to involve a number of individual tests that could be collated into a prescribing algorithm for biological drug selection to be used in clinical practice. Objectives: To quantify patient preferences for an algorithm‐based approach to prescribing biologics (‘biologic calculator’) in psoriasis. Methods: An online survey comprising a discrete choice experiment (DCE) was conducted to elicit the preferences of two purposive samples of adults living with psoriasis in the UK, identified from a psoriasis patient organization (Psoriasis Association) and an online panel provider (Dynata). Respondents chose between two biologic calculators and conventional prescribing described using five attributes: treatment delay; positive predictive value; negative predictive value; risk of infection; and cost saving to the National Health Service. Each participant selected their preferred alternative from six hypothetical choice sets. Additional data, including sociodemographic characteristics, were collected. Choice data were analysed using conditional logit and fully correlated random parameters logit models. Results: Data from 212 respondents (67 from the Psoriasis Association and 145 from Dynata) were analysed. The signs of all estimated coefficients were consistent with a priori expectations. Respondents had a strong preference for a high predictive accuracy and avoiding serious infection, but there was evidence of systematic differences in preferences between the samples. Conclusions: This study indicates that individuals with psoriasis would value a biologic calculator and suggested that such a biologic calculator should have sufficient accuracy to predict future response and risk of serious infection from the biologic.
    • Patient‐relevant health outcomes for hemophilia care: Development of an international standard outcomes set

      van Balen, Erna C.; orcid: 0000-0002-3678-6581; O'Mahony, Brian; Cnossen, Marjon H.; Dolan, Gerard; Blanchette, Victor S.; Fischer, Kathelijn; Gue, Deborah; O'Hara, Jamie; Iorio, Alfonso; orcid: 0000-0002-3331-8766; Jackson, Shannon; et al. (2021-03-06)
      Abstract: Background: Patient‐relevant health outcomes for persons with hemophilia should be identified and prioritized to optimize and individualize care for persons with hemophilia. Therefore, an international group of persons with hemophilia and multidisciplinary health care providers set out to identify a globally applicable standard set of health outcomes relevant to all individuals with hemophilia. Methods: A systematic literature search was performed to identify possible health outcomes and risk adjustment variables. Persons with hemophilia and multidisciplinary health care providers were involved in an iterative nominal consensus process to select the most important health outcomes and risk adjustment variables for persons with hemophilia. Recommendations were made for outcome measurement instruments. Results: Persons with hemophilia were defined as all men and women with an X‐linked inherited bleeding disorder caused by a deficiency of coagulation factor VIII or IX with plasma activity levels <40 IU/dL. We recommend collecting the following 10 health outcomes at least annually, if applicable: (i) cure, (ii) impact of disease on life expectancy, (iii) ability to engage in normal daily activities, (iv) severe bleeding episodes, (v) number of days lost from school or work, (vi) chronic pain, (vii) disease and treatment complications, (viii) sustainability of physical functioning, (ix) social functioning, and (x) mental health. Validated clinical as well as patient‐reported outcome measurement instruments were endorsed. Demographic factors, baseline clinical factors, and treatment factors were identified as risk‐adjustment variables. Conclusion: A consensus‐based international set of health outcomes relevant to all persons with hemophilia, and corresponding measurement instruments, was identified for use in clinical care to facilitate harmonized longitudinal monitoring and comparison of outcomes.
    • Patronage and Power in the Medieval Welsh March: One Family’s Story, by David Stephenson

      Roberts, Sara Elin (Oxford University Press (OUP), 2022-09-08)
    • PDP in the curriculum - how far have we come?

      Done, Judith; Univesity of Chester (2007-06-01)
      This presentation discusses the extent to which the University of Chester's revised academic framework will raise the profile of personal development portfolios and career development learning. The potential impact on the student experience will also be explored.
    • Pension eligibility rules and the local causal effect of retirement on cognitive functioning

      Fé, Eduardo; email: eduardo.fe@manchester.ac.uk (2021-03-23)
      Abstract: We propose an identification framework to evaluate the exclusion restriction in a fuzzy regression discontinuity setting, by adopting results from the literature on partial identification with invalid instrumental variables. With this framework, we provide new estimates of the effect of retirement on cognitive functioning and the first empirical analysis of the validity of an age‐based instrumental variable for retirement. Point estimates suggest an insignificant negative effect of retirement on cognitive functioning. Partial identification regions qualify this finding by suggesting that if retirement is, in fact, detrimental for cognitive functioning, then large drops are unlikely. Second, data alone cannot identify the sign of the treatment effect. In fact, our results support improvements in cognitive functioning following retirement. The bounds analysis suggest that, when studying the impact of retirement, the validity of eligibility as an instrumental variable depends on the time period considered for the analysis and that violations of the exclusion restriction are likely already in very small intervals of 8 months around the cut‐off in regression discontinuity designs.
    • Pentecostalism: A democratizing, liberating force for black women?

      McDonald, Patrice (Informa UK Limited, 2022-08-08)
    • Pentecostalism: A democratizing, liberating force for black women?

      McDonald, Patrice (Informa UK Limited, 2022-08-08)