• Reading Hilary Mantel: Haunted Decades

      Pollard, Eileen (Oxford University Press (OUP), 2021-07-10)
    • Real-time monitoring of crystallization from solution by using an interdigitated array electrode sensor.

      Tong, Jincheng; orcid: 0000-0001-7762-1460; Doumbia, Amadou; orcid: 0000-0002-4136-9029; Turner, Michael L; orcid: 0000-0003-2853-5632; Casiraghi, Cinzia; orcid: 0000-0001-7185-0377 (2021-04-27)
      Monitoring crystallization events in real-time is challenging but crucial for understanding the molecular dynamics associated with nucleation and crystal growth, some of nature's most ubiquitous phenomena. Recent observations have suggested that the traditional nucleation model, which describes the nucleus having already the final crystal structure, may not be valid. It appears that the molecular assembly can range during nucleation from crystalline to partially ordered to totally amorphous phases, and can change its structure during the crystallization process. Therefore, it is of critical importance to develop methods that are able to provide real-time monitoring of the molecular interactions with high temporal resolution. Here, we demonstrate that a simple and scalable approach based on interdigitated electrode array sensors (IESs) is able to provide insights on the dynamics of the crystallization process with a temporal resolution of 15 ms.
    • Real-world evidence on Kovaltry (81-8973) in children with moderate or severe hemophilia A in Europe: a nested cohort analysis

      O’Hara, Jamie; Hirst, Ceri; orcid: 0000-0001-9094-2437; email: ceri.hirst@bayer.com; Cabre Marquez, Jose Francisco; Burke, Tom (BioMed Central, 2021-01-15)
      Abstract: Background: Untreated hemophilia A patients may experience recurrent bleeding events leading to debilitating joint damages. While RCT and pharmacokinetic data support the value of Kovaltry [an unmodified full-length recombinant factor VIII (FVIII) product], real world evidence in children is lacking. This report describes a descriptive and multivariate analysis of the effectiveness of Kovaltry in children with hemophilia A in the real-world setting, using data from medical chart abstraction and cross-sectional surveys of physicians, patients, and caregivers. Results: Male patients aged < 18 years with moderate or severe hemophilia A, residing in five European countries and treated with FVIII were studied. The co-primary endpoints were the annualized bleeding rate (ABR) and the annual FVIII utilization rate. Twenty nine patients treated with Kovaltry were included, of whom 93% had severe disease and 75% were on continuous prophylactic treatment. The mean ABR was 2.66 ± 2.06, with rates decreasing with age. The children received on average 2.45 infusions per week, consistent across age groups (median 3; range 1–3). There were no reports of inhibitor development or adverse events in the study (AEs), and all patients were satisfied or very satisfied with the treatment. An exploratory multivariate analysis suggests no significant difference in ABR or units utilized between Kovaltry and some extended half life products in children with severe hemophilia A, though characteristics of these patient cohorts were markedly different. Conclusion: This analysis demonstrates the effectiveness and safety of Kovaltry in a pan-European pediatric population with severe hemophilia A.
    • Reasons for indoor tanning use and the acceptability of alternatives: A qualitative study.

      Lyons, Stephanie; Lorigan, Paul; Green, Adele C; Ferguson, Ashley; Epton, Tracy; email: tracy.epton@manchester.ac.uk (2021-08-20)
      Using indoor tanning devices is associated with substantial health consequences, such as an increased risk of melanoma and other skin cancers. Many people including minors and some at high risk of skin cancer continue to use these devices. In the absence of effective restrictions on use, it is important that behaviour change interventions are designed to reduce indoor tanning. To explore reasons for use of indoor tanning devices and the acceptability of alternatives in adult users residing in North-West England. Participants were required to be current indoor tanners aged 18 years and above and were recruited online. Twenty-one participants took part in either a focus group or semi-structured interview. An inductive thematic analysis was conducted. Six themes were identified: psychological benefits; improving physical health; denial of health risks; alternatives do not meet psychological needs; alternatives do not meet physical needs; and perceived side-effects. Participants used indoor tanning devices to improve their self-esteem and to prevent sun damage to their skin (by gaining a 'base tan'). Participants appeared to justify their usage by responding defensively to avoid accepting they were at risk, exaggerating the benefits of indoor tanning, and discounting alternatives to indoor tanning. Alternatives to indoor tanning were perceived as risky for health, inadequate to provide the desired aesthetic, and incapable of meeting their self-esteem needs. Interventions to reduce indoor tanning behaviour should increase sources of self-esteem other than appearance, increase media literacy and address defensive responses to information around indoor tanning and alternatives. Further research is needed to develop these interventions and assess their feasibility. [Abstract copyright: Copyright © 2021. Published by Elsevier Ltd.]
    • Reasons for success and lessons learnt from nanoscale vaccines against COVID-19.

      Kisby, Thomas; orcid: 0000-0002-8432-7910; Yilmazer, Açelya; orcid: 0000-0003-2712-7450; Kostarelos, Kostas; orcid: 0000-0002-2224-6672; email: kostas.kostarelos@manchester.ac.uk (2021-08)
    • Recent Advances in Enzymatic and Non-Enzymatic Electrochemical Glucose Sensing

      Hassan, Mohamed H.; orcid: 0000-0002-0832-8559; email: Mohamed.hassan@manchester.ac.uk; Vyas, Cian; orcid: 0000-0001-6030-1962; email: cian.vyas@manchester.ac.uk; Grieve, Bruce; orcid: 0000-0002-5130-3592; email: bruce.grieve@manchester.ac.uk; Bartolo, Paulo; orcid: 0000-0003-3683-726X; email: paulojorge.dasilvabartolo@manchester.ac.uk (MDPI, 2021-07-08)
      The detection of glucose is crucial in the management of diabetes and other medical conditions but also crucial in a wide range of industries such as food and beverages. The development of glucose sensors in the past century has allowed diabetic patients to effectively manage their disease and has saved lives. First-generation glucose sensors have considerable limitations in sensitivity and selectivity which has spurred the development of more advanced approaches for both the medical and industrial sectors. The wide range of application areas has resulted in a range of materials and fabrication techniques to produce novel glucose sensors that have higher sensitivity and selectivity, lower cost, and are simpler to use. A major focus has been on the development of enzymatic electrochemical sensors, typically using glucose oxidase. However, non-enzymatic approaches using direct electrochemistry of glucose on noble metals are now a viable approach in glucose biosensor design. This review discusses the mechanisms of electrochemical glucose sensing with a focus on the different generations of enzymatic-based sensors, their recent advances, and provides an overview of the next generation of non-enzymatic sensors. Advancements in manufacturing techniques and materials are key in propelling the field of glucose sensing, however, significant limitations remain which are highlighted in this review and requires addressing to obtain a more stable, sensitive, selective, cost efficient, and real-time glucose sensor.
    • Recent advances in the chemistry of ketyl radicals.

      Péter, Áron; email: david.j.procter@manchester.ac.uk; Agasti, Soumitra; Knowles, Oliver; Pye, Emma; Procter, David J (2021-03-23)
      Ketyl radicals are valuable reactive intermediates for synthesis and are used extensively to construct complex, functionalized products from carbonyl substrates. Single electron transfer (SET) reduction of the C[double bond, length as m-dash]O bond of aldehydes and ketones is the classical approach for the formation of ketyl radicals and metal reductants are the archetypal reagents employed. The past decade has, however, witnessed significant advances in the generation and harnessing of ketyl radicals. This tutorial review highlights recent, exciting developments in the chemistry of ketyl radicals by comparing the varied contemporary - for example, using photoredox catalysts - and more classical approaches for the generation and use of ketyl radicals. The review will focus on different strategies for ketyl radical generation, their creative use in new synthetic protocols, strategies for the control of enantioselectivity, and detailed mechanisms where appropriate.
    • Recent Progress on Semiconductor-Interface Facing Clinical Biosensing

      Zhang, Mingrui; email: mingrui.zhang-2@student.manchester.ac.uk; Adkins, Mitchell; email: mitchelladkins@oakland.edu; Wang, Zhe; orcid: 0000-0003-3762-3167; email: zhewang@oakland.edu (MDPI, 2021-05-16)
      Semiconductor (SC)-based field-effect transistors (FETs) have been demonstrated as amazing enhancer gadgets due to their delicate interface towards surface adsorption. This leads to their application as sensors and biosensors. Additionally, the semiconductor material has enormous recognizable fixation extends, high affectability, high consistency for solid detecting, and the ability to coordinate with other microfluidic gatherings. This review focused on current progress on the semiconductor-interfaced FET biosensor through the fundamental interface structure of sensor design, including inorganic semiconductor/aqueous interface, photoelectrochemical interface, nano-optical interface, and metal-assisted interface. The works that also point to a further advancement for the trademark properties mentioned have been reviewed here. The emergence of research on the organic semiconductor interface, integrated biosensors with Complementary metal–oxide–semiconductor (CMOS)-compatible, metal-organic frameworks, has accelerated the practical application of biosensors. Through a solid request for research along with sensor application, it will have the option to move forward the innovative sensor with the extraordinary semiconductor interface structure.
    • Reciprocal priming between receptor tyrosine kinases at recycling endosomes orchestrates cellular signalling outputs

      Smith, Michael P; Ferguson, Harriet R; orcid: 0000-0002-0283-4629; Ferguson, Jennifer; Zindy, Egor; Kowalczyk, Katarzyna M; Kedward, Thomas; Bates, Christian; Parsons, Joseph; Watson, Joanne; Chandler, Sarah; orcid: 0000-0003-3981-8590; et al. (2021-06-04)
      Abstract: Integration of signalling downstream of individual receptor tyrosine kinases (RTKs) is crucial to fine‐tune cellular homeostasis during development and in pathological conditions, including breast cancer. However, how signalling integration is regulated and whether the endocytic fate of single receptors controls such signalling integration remains poorly elucidated. Combining quantitative phosphoproteomics and targeted assays, we generated a detailed picture of recycling‐dependent fibroblast growth factor (FGF) signalling in breast cancer cells, with a focus on distinct FGF receptors (FGFRs). We discovered reciprocal priming between FGFRs and epidermal growth factor (EGF) receptor (EGFR) that is coordinated at recycling endosomes. FGFR recycling ligands induce EGFR phosphorylation on threonine 693. This phosphorylation event alters both FGFR and EGFR trafficking and primes FGFR‐mediated proliferation but not cell invasion. In turn, FGFR signalling primes EGF‐mediated outputs via EGFR threonine 693 phosphorylation. This reciprocal priming between distinct families of RTKs from recycling endosomes exemplifies a novel signalling integration hub where recycling endosomes orchestrate cellular behaviour. Therefore, targeting reciprocal priming over individual receptors may improve personalized therapies in breast and other cancers.
    • Reciprocal transcription factor networks govern tissue-resident ILC3 subset function and identity.

      Fiancette, Rémi; orcid: 0000-0003-1531-9770; Finlay, Conor M; Willis, Claire; Bevington, Sarah L; Soley, Jake; orcid: 0000-0001-7131-2560; Ng, Sky T H; Baker, Syed Murtuza; orcid: 0000-0002-6633-333X; Andrews, Simon; orcid: 0000-0002-5006-3507; Hepworth, Matthew R; orcid: 0000-0002-9613-7858; email: matthew.hepworth@manchester.ac.uk; Withers, David R; orcid: 0000-0003-3757-7594; email: d.withers@bham.ac.uk (2021-09-23)
      Innate lymphoid cells (ILCs) are guardians of mucosal immunity, yet the transcriptional networks that support their function remain poorly understood. We used inducible combinatorial deletion of key transcription factors (TFs) required for ILC development (RORγt, RORα and T-bet) to determine their necessity in maintaining ILC3 identity and function. Both RORγt and RORα were required to preserve optimum effector functions; however, RORα was sufficient to support robust interleukin-22 production among the lymphoid tissue inducer (LTi)-like ILC3 subset, but not natural cytotoxicity receptor (NCR) ILC3s. Lymphoid tissue inducer-like ILC3s persisted with only selective loss of phenotype and effector functions even after the loss of both TFs. In contrast, continued RORγt expression was essential to restrain transcriptional networks associated with type 1 immunity within NCR ILC3s, which coexpress T-bet. Full differentiation to an ILC1-like population required the additional loss of RORα. Together, these data demonstrate how TF networks integrate within mature ILCs after development to sustain effector functions, imprint phenotype and restrict alternative differentiation programs. [Abstract copyright: © 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.]
    • Recognition of Design Fixation via Body Language Using Computer Vision

      Academic Editor: Zhang, Kai; Yang, Zhongliang; email: yzl@dhu.edu.cn; Chen, Yumiao; orcid: 0000-0002-2702-4649; email: 181603042@qq.com; Zhang, Song; email: zhangrime@gmail.com (Hindawi, 2021-08-27)
      The main objective of this study is to recognize design fixation accurately and effectively. First, we conducted an experiment to record the videos of design process and design sketches from 12 designers for 15 minutes. Then, we executed a video analysis of body language in designers, correlating body language to the presence of design fixation, as judged by a panel of six experts. We found that three body language types were significantly correlated to fixation. A two-step hybrid recognition model of design fixation based on body language was proposed. The first-step recognition model of body language using transfer learning based on a pretrained VGG-16 convolutional neural network was constructed. The average recognition rate achieved by the VGG-16 model was 92.03%. Then, the frames of recognized body language were used as input vectors to the second-step fixation classification model based on support vector machine (SVM). The average recognition rate for the fixation state achieved by the SVM model was 79.11%. The impact of the work could be that the fixation can be detected not only by the sketch outcomes but also by monitoring the movements, expressions, and gestures of designers, as it is happening by monitoring the movements, expressions, and gestures of designers.
    • Recommendations for Transdisciplinary Professional Competencies and Ethics for Animal-Assisted Therapies and Interventions

      Trevathan-Minnis, Melissa; email: drtrevathanminnis@gmail.com; Johnson, Amy; orcid: 0000-0003-3536-9193; email: dramyjohnsonlpc@gmail.com; Howie, Ann R.; email: humananimalsolutions@comcast.net (MDPI, 2021-12-02)
      AAI is a transdisciplinary field that has grown exponentially in recent decades. This growth has not always been synergistic across fields, creating a need for more consistent language and standards, a call for which many professionals in the field have made. Under the umbrella of human−animal interactions (HAI) is animal-assisted interventions (AAIs), which have a more goal-directed intention with animals who have been assessed for therapeutic, educational, or vocational work. The current article offers a brief history and efficacy of HAI, describes the limitations and gaps within the field and recommends a new set of competencies and guidelines that seek to create some of the needed common language and standards for AAI work to address these limitations.
    • Recommendations for Transdisciplinary Professional Competencies and Ethics for Animal-Assisted Therapies and Interventions.

      Trevathan-Minnis, Melissa; Johnson, Amy; orcid: 0000-0003-3536-9193; Howie, Ann R (2021-12-02)
      AAI is a transdisciplinary field that has grown exponentially in recent decades. This growth has not always been synergistic across fields, creating a need for more consistent language and standards, a call for which many professionals in the field have made. Under the umbrella of human-animal interactions (HAI) is animal-assisted interventions (AAIs), which have a more goal-directed intention with animals who have been assessed for therapeutic, educational, or vocational work. The current article offers a brief history and efficacy of HAI, describes the limitations and gaps within the field and recommends a new set of competencies and guidelines that seek to create some of the needed common language and standards for AAI work to address these limitations.
    • Recomposing persons: Scavenging and storytelling in a birth cohort archive

      Tinkler, Penny; orcid: 0000-0002-9918-9821; email: penny.tinkler@manchester.ac.uk; Cruz, Resto; orcid: 0000-0003-2621-6232; Fenton, Laura (SAGE Publications, 2021-03-08)
      Birth cohort studies can be used not only to generate population-level quantitative data, but also to recompose persons. The crux is how we understand data and persons. Recomposition entails scavenging for various (including unrecognised) data. It foregrounds the perspective and subjectivity of survey participants, but without forgetting the partiality and incompleteness of the accounts that it may generate. Although interested in the singularity of individuals, it attends to the historical and relational embeddedness of personhood. It examines the multiple and complex temporalities that suffuse people’s lives, hence departing from linear notions of the life course. It implies involvement, as well as reflexivity, on the part of researchers. It embraces the heterogeneity and transformations over time of scientific archives and the interpretive possibilities, as well as incompleteness, of birth cohort studies data. Interested in the unfolding of lives over time, it also shines light on meaningful biographical moments.
    • Reconciling Egg- and Antigen-Based Estimates of Schistosoma mansoni Clearance and Reinfection: A Modeling Study

      Clark, Jessica; orcid: 0000-0003-1692-899X; Moses, Arinaitwe; Nankasi, Andrina; Faust, Christina L; Moses, Adriko; Ajambo, Diana; Besigye, Fred; Atuhaire, Aaron; Wamboko, Aidah; Carruthers, Lauren V; et al. (Oxford University Press (OUP), 2021-08-06)
      Abstract Background Despite decades of interventions, 240 million people have schistosomiasis. Infections cannot be directly observed, and egg-based Kato-Katz thick smears lack sensitivity, affected treatment efficacy and reinfection rate estimates. The point-of-care circulating cathodic antigen (referred to from here as POC-CCA+) test is advocated as an improvement on the Kato-Katz method, but improved estimates are limited by ambiguities in the interpretation of trace results. Method We collected repeated Kato-Katz egg counts from 210 school-aged children and scored POC-CCA tests according to the manufacturer’s guidelines (referred to from here as POC-CCA+) and the externally developed G score. We used hidden Markov models parameterized with Kato-Katz; Kato-Katz and POC-CCA+; and Kato-Katz and G-Scores, inferring latent clearance and reinfection probabilities at four timepoints over six-months through a more formal statistical reconciliation of these diagnostics than previously conducted. Our approach required minimal but robust assumptions regarding trace interpretations. Results Antigen-based models estimated higher infection prevalence across all timepoints compared with the Kato-Katz model, corresponding to lower clearance and higher reinfection estimates. Specifically, pre-treatment prevalence estimates were 85% (Kato-Katz; 95% CI: 79%–92%), 99% (POC-CCA+; 97%–100%) and 98% (G-Score; 95%–100%). Post-treatment, 93% (Kato-Katz; 88%–96%), 72% (POC-CCA+; 64%–79%) and 65% (G-Score; 57%–73%) of those infected were estimated to clear infection. Of those who cleared infection, 35% (Kato-Katz; 27%–42%), 51% (POC-CCA+; 41%–62%) and 44% (G-Score; 33%–55%) were estimated to have been reinfected by 9-weeks. Conclusions Treatment impact was shorter-lived than Kato-Katz–based estimates alone suggested, with lower clearance and rapid reinfection. At 3 weeks after treatment, longer-term clearance dynamics are captured. At 9 weeks after treatment, reinfection was captured, but failed clearance could not be distinguished from rapid reinfection. Therefore, frequent sampling is required to understand these important epidemiological dynamics.
    • Reconciling egg- and antigen-based estimates of Schistosoma mansoni clearance and reinfection: a modelling study

      Clark, Jessica; orcid: 0000-0003-1692-899X; Arinaitwe, Moses; Nankasi, Andrina; Faust, Christina L; Moses, Adriko; Ajambo, Diana; Besigye, Fred; Atuhaire, Alon; Wamboko, Aidah; Carruthers, Lauren V; et al. (Oxford University Press (OUP), 2021-08-06)
      Abstract Background 240-million people have schistosomiasis despite decades of interventions. Infections cannot be directly observed, and egg-based Kato-Katz thick smears lack sensitivity, impacting treatment efficacy and reinfection rate estimates. The Point-of-Care Circulating Cathodic Antigen test (POC-CCA) is advocated as an improvement upon the Kato-Katz, however improved estimates are limited by ambiguities in the interpretation of Trace results. Method We collected repeated Kato-Katz counts from 210 school-aged children and scored POC-CCAs according to manufacturer’s guidelines (POC-CCA+) and the externally developed G-Score. We used Hidden Markov Models parameterised with Kato-Katz; Kato-Katz and POC-CCA+; and Kato-Katz and G-Scores, inferring latent clearance and reinfection probabilities at four timepoints over six-months through a more formal statistical reconciliation of these diagnostics than previously conducted. Our approach required minimal but robust assumptions regarding Trace interpretations. Results Antigen-based models estimated higher infection prevalence across all timepoints compared with the Kato-Katz model, corresponding to lower clearance and higher reinfection estimates. Specifically, pre-treatment prevalence estimates were 85% (Kato-Katz; 95% CI: 79-92%), 99% (POC-CCA+; 97-100%) and 98% (G-Score; 95-100%). Post-treatment, 93% (Kato-Katz; 88-96%), 72% (POC-CCA+; 64-79%) and 65% (G-Score; 57-73%) of those infected were estimated to clear infection. Of those who cleared infection, 35% (Kato-Katz; 27-42%), 51% (POC-CCA+; 41-62%) and 44% (G-Score; 33-55%) were estimated to have been reinfected by nine-weeks. Conclusion Treatment impact was shorter-lived than only Kato-Katz-based estimates suggested, with lower clearance and rapid reinfection. Three-weeks-post-treatment captured longer-term clearance dynamics. Nine-weeks-post-treatment captured reinfection, but alone could not discern between failed clearance and rapid reinfection. Therefore, frequent sampling is required to understand these important epidemiological dynamics.
    • Reconciling egg- and antigen-based estimates of Schistosoma mansoni clearance and reinfection: a modelling study.

      Clark, Jessica; orcid: 0000-0003-1692-899X; Arinaitwe, Moses; Nankasi, Andrina; Faust, Christina L; Moses, Adriko; Ajambo, Diana; Besigye, Fred; Atuhaire, Alon; Wamboko, Aidah; Carruthers, Lauren V; et al. (2021-08-06)
      240-million people have schistosomiasis despite decades of interventions. Infections cannot be directly observed, and egg-based Kato-Katz thick smears lack sensitivity, impacting treatment efficacy and reinfection rate estimates. The Point-of-Care Circulating Cathodic Antigen test (POC-CCA) is advocated as an improvement upon the Kato-Katz, however improved estimates are limited by ambiguities in the interpretation of Trace results. We collected repeated Kato-Katz counts from 210 school-aged children and scored POC-CCAs according to manufacturer's guidelines (POC-CCA+) and the externally developed G-Score. We used Hidden Markov Models parameterised with Kato-Katz; Kato-Katz and POC-CCA+; and Kato-Katz and G-Scores, inferring latent clearance and reinfection probabilities at four timepoints over six-months through a more formal statistical reconciliation of these diagnostics than previously conducted. Our approach required minimal but robust assumptions regarding Trace interpretations. Antigen-based models estimated higher infection prevalence across all timepoints compared with the Kato-Katz model, corresponding to lower clearance and higher reinfection estimates. Specifically, pre-treatment prevalence estimates were 85% (Kato-Katz; 95% CI: 79-92%), 99% (POC-CCA+; 97-100%) and 98% (G-Score; 95-100%). Post-treatment, 93% (Kato-Katz; 88-96%), 72% (POC-CCA+; 64-79%) and 65% (G-Score; 57-73%) of those infected were estimated to clear infection. Of those who cleared infection, 35% (Kato-Katz; 27-42%), 51% (POC-CCA+; 41-62%) and 44% (G-Score; 33-55%) were estimated to have been reinfected by nine-weeks. Treatment impact was shorter-lived than only Kato-Katz-based estimates suggested, with lower clearance and rapid reinfection. Three-weeks-post-treatment captured longer-term clearance dynamics. Nine-weeks-post-treatment captured reinfection, but alone could not discern between failed clearance and rapid reinfection. Therefore, frequent sampling is required to understand these important epidemiological dynamics. [Abstract copyright: © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.]
    • Recovery capital in the context of homelessness, high levels of alcohol consumption, and adverse significant life events

      Ross-Houle, Kim; Porcellato, Lorna; orcid: 0000-0002-8656-299X (Informa UK Limited, 2021-12-16)
    • Recovery of free volume in PIM-1 membranes through alcohol vapor treatment

      Almansour, Faiz; Alberto, Monica; Bhavsar, Rupesh S.; Fan, Xiaolei; Budd, Peter M.; Gorgojo, Patricia; email: p.gorgojo@manchester.ac.uk (Higher Education Press, 2021-02-10)
      Abstract: Physical aging is currently a major obstacle for the commercialization of PIM-1 membranes for gas separation applications. A well-known approach to reversing physical aging effects of PIM-1 membranes at laboratory scale is soaking them in lower alcohols, such as methanol and ethanol. However, this procedure does not seem applicable at industrial level, and other strategies must be investigated. In this work, a regeneration method with alcohol vapors (ethanol or methanol) was developed to recover permeability of aged PIM-1 membranes, in comparison with the conventional soaking-in-liquid approach. The gas permeability and separation performance, before and post the regeneration methods, were assessed using a binary mixture of CO2 and CH4 (1:1, v:v). Our results show that an 8-hour methanol vapor treatment was sufficient to recover the original gas permeability, reaching a CO2 permeability > 7000 barrer.
    • Recurrent KCNT2 missense variants affecting p.Arg190 result in a recognizable phenotype

      Jackson, Adam; orcid: 0000-0002-3674-3960; email: adam.jackson-5@postgrad.manchester.ac.uk; Banka, Siddharth; orcid: 0000-0002-8527-2210; Stewart, Helen; orcid: 0000-0002-1196-3000; Genomics England Research Consortium; Robinson, Hannah; Lovell, Simon; Clayton‐Smith, Jill (John Wiley & Sons, Inc., 2021-06-01)
      Abstract: KCNT2 variants resulting in substitutions affecting the Arg190 residue have been shown to cause epileptic encephalopathy and a recognizable facial gestalt. We report two additional individuals with intellectual disability, dysmorphic features, hypertrichosis, macrocephaly and the same de novo KCNT2 missense variants affecting the Arg190 residue as previously described. Notably, neither patient has epilepsy. Homology modeling of these missense variants revealed that they are likely to disrupt the stabilization of a closed channel conformation of KCNT2 resulting in a constitutively open state. This is the first report of pathogenic variants in KCNT2 causing a developmental phenotype without epilepsy.