• Cell-specific conditional deletion of interleukin-1 (IL-1) ligands and its receptors: a new toolbox to study the role of IL-1 in health and disease

      Pinteaux, Emmanuel; orcid: 0000-0002-9986-4401; email: emmanuel.pinteaux@manchester.ac.uk; Abdulaal, Wesam H; Mufazalov, Ilgiz A; Humphreys, Neil E; Simonsen-Jackson, Maj; Francis, Sheila; Müller, Werner; Waisman, Ari (Springer Berlin Heidelberg, 2020-05-29)
      Abstract: The pro-inflammatory cytokine interleukin-1 (IL-1) plays a key role in many physiological processes and during the inflammatory and immune response to most common diseases. IL-1 exists as two agonists, IL-1α and IL-1β that bind to the only signaling IL-1 type 1 receptor (IL-1R1), while a second decoy IL-1 type 2 receptor (IL-1R2) binds both forms of IL-1 without inducing cell signaling. The field of immunology and inflammation research has, over the past 35 years, unraveled many mechanisms of IL-1 actions, through in vitro manipulation of the IL-1 system or by using genetically engineered mouse models that lack either member of the IL-1 family in ubiquitous constitutive manner. However, the limitation of global mouse knockout technology has significantly hampered our understanding of the precise mechanisms of IL-1 actions in animal models of disease. Here we report and review the recent generation of new conditional mouse mutants in which exons of Il1a, Il1b, Il1r1, and Il1r2 genes flanked by loxP sites (fl/fl) can be deleted in cell-/tissue-specific constitutive or inducible manner by Cre recombinase expression. Hence, IL-1αfl/fl, IL-1βfl/fl, IL-1R1fl/fl, and IL-1R2fl/fl mice constitute a new toolbox that will provide a step change in our understanding of the cell-specific role of IL-1 and its receptor in health and disease and the potential development of targeted IL-1 therapies.
    • Challenges in cell transplantation for muscular dystrophy.

      Galli, Francesco; Mouly, Vincent; Butler-Browne, Gillian; Cossu, Giulio; email: giulio.cossu@manchester.ac.uk (2021-11-01)
      For decades now, cell transplantation has been considered a possible therapeutic strategy for muscular dystrophy, but failures have largely outnumbered success or at least encouraging outcomes. In this review we will briefly recall the history of cell transplantation, discuss the peculiar features of skeletal muscle, and dystrophic skeletal muscle in particular, that make the procedure complicated and inefficient. As there are many recent and exhaustive reviews on the various myogenic cell types that have been or will be transplanted, we will only briefly describe them and refer the reader to these reviews. Finally, we will discuss possible strategies to overcome the hurdles that prevent biological efficacy and hence clinical success. [Abstract copyright: Copyright © 2021. Published by Elsevier Inc.]
    • Challenges in control of COVID-19: short doubling time and long delay to effect of interventions

      Pellis, Lorenzo; orcid: 0000-0002-3436-6487; email: lorenzo.pellis@manchester.ac.uk; Scarabel, Francesca; orcid: 0000-0003-0250-4555; Stage, Helena B.; orcid: 0000-0001-9938-8452; Overton, Christopher E.; Chappell, Lauren H. K.; Fearon, Elizabeth; Bennett, Emma; Lythgoe, Katrina A.; House, Thomas A.; orcid: 0000-0001-5835-8062; Hall, Ian; orcid: 0000-0002-3033-2335; et al. (The Royal Society, 2021-05-31)
      Early assessments of the growth rate of COVID-19 were subject to significant uncertainty, as expected with limited data and difficulties in case ascertainment, but as cases were recorded in multiple countries, more robust inferences could be made. Using multiple countries, data streams and methods, we estimated that, when unconstrained, European COVID-19 confirmed cases doubled on average every 3 days (range 2.2–4.3 days) and Italian hospital and intensive care unit admissions every 2–3 days; values that are significantly lower than the 5–7 days dominating the early published literature. Furthermore, we showed that the impact of physical distancing interventions was typically not seen until at least 9 days after implementation, during which time confirmed cases could grow eightfold. We argue that such temporal patterns are more critical than precise estimates of the time-insensitive basic reproduction number R0 for initiating interventions, and that the combination of fast growth and long detection delays explains the struggle in countries' outbreak response better than large values of R0 alone. One year on from first reporting these results, reproduction numbers continue to dominate the media and public discourse, but robust estimates of unconstrained growth remain essential for planning worst-case scenarios, and detection delays are still key in informing the relaxation and re-implementation of interventions. This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
    • Challenges in control of COVID-19: short doubling time and long delay to effect of interventions

      Pellis, Lorenzo; orcid: 0000-0002-3436-6487; email: lorenzo.pellis@manchester.ac.uk; Scarabel, Francesca; orcid: 0000-0003-0250-4555; Stage, Helena B.; orcid: 0000-0001-9938-8452; Overton, Christopher E.; orcid: 0000-0002-8433-4010; Chappell, Lauren H. K.; orcid: 0000-0001-8654-2756; Fearon, Elizabeth; orcid: 0000-0001-5574-251X; Bennett, Emma; orcid: 0000-0001-7188-4315; Lythgoe, Katrina A.; orcid: 0000-0002-7089-7680; House, Thomas A.; orcid: 0000-0001-5835-8062; Hall, Ian; orcid: 0000-0002-3033-2335; et al. (The Royal Society, 2021-05-31)
      Early assessments of the growth rate of COVID-19 were subject to significant uncertainty, as expected with limited data and difficulties in case ascertainment, but as cases were recorded in multiple countries, more robust inferences could be made. Using multiple countries, data streams and methods, we estimated that, when unconstrained, European COVID-19 confirmed cases doubled on average every 3 days (range 2.2–4.3 days) and Italian hospital and intensive care unit admissions every 2–3 days; values that are significantly lower than the 5–7 days dominating the early published literature. Furthermore, we showed that the impact of physical distancing interventions was typically not seen until at least 9 days after implementation, during which time confirmed cases could grow eightfold. We argue that such temporal patterns are more critical than precise estimates of the time-insensitive basic reproduction number R0 for initiating interventions, and that the combination of fast growth and long detection delays explains the struggle in countries' outbreak response better than large values of R0 alone. One year on from first reporting these results, reproduction numbers continue to dominate the media and public discourse, but robust estimates of unconstrained growth remain essential for planning worst-case scenarios, and detection delays are still key in informing the relaxation and re-implementation of interventions. This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
    • Challenges in control of COVID-19: short doubling time and long delay to effect of interventions

      Pellis, Lorenzo; orcid: 0000-0002-3436-6487; email: lorenzo.pellis@manchester.ac.uk; Scarabel, Francesca; orcid: 0000-0003-0250-4555; Stage, Helena B.; orcid: 0000-0001-9938-8452; Overton, Christopher E.; orcid: 0000-0002-8433-4010; Chappell, Lauren H. K.; orcid: 0000-0001-8654-2756; Fearon, Elizabeth; orcid: 0000-0001-5574-251X; Bennett, Emma; orcid: 0000-0001-7188-4315; Lythgoe, Katrina A.; orcid: 0000-0002-7089-7680; House, Thomas A.; orcid: 0000-0001-5835-8062; Hall, Ian; orcid: 0000-0002-3033-2335; et al. (The Royal Society, 2021-05-31)
      Early assessments of the growth rate of COVID-19 were subject to significant uncertainty, as expected with limited data and difficulties in case ascertainment, but as cases were recorded in multiple countries, more robust inferences could be made. Using multiple countries, data streams and methods, we estimated that, when unconstrained, European COVID-19 confirmed cases doubled on average every 3 days (range 2.2–4.3 days) and Italian hospital and intensive care unit admissions every 2–3 days; values that are significantly lower than the 5–7 days dominating the early published literature. Furthermore, we showed that the impact of physical distancing interventions was typically not seen until at least 9 days after implementation, during which time confirmed cases could grow eightfold. We argue that such temporal patterns are more critical than precise estimates of the time-insensitive basic reproduction number R0 for initiating interventions, and that the combination of fast growth and long detection delays explains the struggle in countries' outbreak response better than large values of R0 alone. One year on from first reporting these results, reproduction numbers continue to dominate the media and public discourse, but robust estimates of unconstrained growth remain essential for planning worst-case scenarios, and detection delays are still key in informing the relaxation and re-implementation of interventions. This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
    • Changes in Physical Activity and Sedentary Behaviour Due to Enforced COVID-19-Related Lockdown and Movement Restrictions: A Protocol for a Systematic Review and Meta-Analysis

      Kite, Chris; orcid: 0000-0003-1342-274X; email: c.kite@chester.ac.uk; Lagojda, Lukasz; email: lukasz.lagojda@uhcw.nhs.uk; Clark, Cain C. T.; orcid: 0000-0002-6610-4617; email: ad0183@coventry.ac.uk; Uthman, Olalekan; orcid: 0000-0002-8567-3081; email: olalekan.uthman@warwick.ac.uk; Denton, Francesca; orcid: 0000-0002-1016-1786; email: dentonf@uni.coventry.ac.uk; McGregor, Gordon; orcid: 0000-0001-8963-9107; email: ac4378@coventry.ac.uk; Harwood, Amy E.; email: ad5104@coventry.ac.uk; Atkinson, Lou; email: l.atkinson1@aston.ac.uk; Broom, David R.; email: ad5173@coventry.ac.uk; Kyrou, Ioannis; orcid: 0000-0002-6997-3439; email: kyrouj@gmail.com; et al. (MDPI, 2021-05-14)
      Prolonged lockdown/restriction measures due to the COVID-19 pandemic have reportedly impacted opportunities to be physically active for a large proportion of the population in affected countries globally. The exact changes to physical activity and sedentary behaviours due to these measures have not been fully studied. Accordingly, the objective of this PROSPERO-registered systematic review is to evaluate the available evidence on physical activity and sedentary behaviours in the general population during COVID-19-related lockdown/restriction measures, compared to prior to restrictions being in place. Defined searches to identify eligible studies published in English, from November 2019 up to the date of submission, will be conducted using the following databases: CENTRAL, MEDLINE, EMBASE, CINAHL, SPORTDiscus, PSYCinfo, Coronavirus Research Database, Public Health Database, Publicly Available Content Database, SCOPUS, and Google Scholar. The applied inclusion criteria were selected to identify observational studies with no restrictions placed on participants, with outcomes regarding physical activity and/or sedentary behaviour during lockdown/restriction measures, and with comparisons for these outcomes to a time when no such measures were in place. Where appropriate, results from included studies will be pooled and effect estimates will be presented in random effects meta-analyses. To the best of our knowledge, this will be the first systematic review to evaluate one complete year of published data on the impact of COVID-19-related lockdown/restriction measures on physical activity and sedentary behaviour. Thus, this systematic review and meta-analysis will constitute the most up-to-date synthesis of published evidence on any such documented changes, and so will comprehensively inform clinical practitioners, public health agencies, researchers, policymakers and the general public regarding the effects of lockdown/restriction measures on both physical activity and sedentary behaviour.
    • Changes in Physical Activity and Sedentary Behaviour Due to Enforced COVID-19-Related Lockdown and Movement Restrictions: A Protocol for a Systematic Review and Meta-Analysis.

      Kite, Chris; orcid: 0000-0003-1342-274X; Lagojda, Lukasz; Clark, Cain C T; orcid: 0000-0002-6610-4617; Uthman, Olalekan; orcid: 0000-0002-8567-3081; Denton, Francesca; orcid: 0000-0002-1016-1786; McGregor, Gordon; orcid: 0000-0001-8963-9107; Harwood, Amy E; Atkinson, Lou; Broom, David R; Kyrou, Ioannis; orcid: 0000-0002-6997-3439; et al. (2021-05-14)
      Prolonged lockdown/restriction measures due to the COVID-19 pandemic have reportedly impacted opportunities to be physically active for a large proportion of the population in affected countries globally. The exact changes to physical activity and sedentary behaviours due to these measures have not been fully studied. Accordingly, the objective of this PROSPERO-registered systematic review is to evaluate the available evidence on physical activity and sedentary behaviours in the general population during COVID-19-related lockdown/restriction measures, compared to prior to restrictions being in place. Defined searches to identify eligible studies published in English, from November 2019 up to the date of submission, will be conducted using the following databases: CENTRAL, MEDLINE, EMBASE, CINAHL, SPORTDiscus, PSYCinfo, Coronavirus Research Database, Public Health Database, Publicly Available Content Database, SCOPUS, and Google Scholar. The applied inclusion criteria were selected to identify observational studies with no restrictions placed on participants, with outcomes regarding physical activity and/or sedentary behaviour during lockdown/restriction measures, and with comparisons for these outcomes to a time when no such measures were in place. Where appropriate, results from included studies will be pooled and effect estimates will be presented in random effects meta-analyses. To the best of our knowledge, this will be the first systematic review to evaluate one complete year of published data on the impact of COVID-19-related lockdown/restriction measures on physical activity and sedentary behaviour. Thus, this systematic review and meta-analysis will constitute the most up-to-date synthesis of published evidence on any such documented changes, and so will comprehensively inform clinical practitioners, public health agencies, researchers, policymakers and the general public regarding the effects of lockdown/restriction measures on both physical activity and sedentary behaviour.
    • Changes in the Management of Patients having Radical Radiotherapy for Lung Cancer during the First Wave of the COVID-19 Pandemic in the UK.

      Banfill, K; email: kathryn.banfill@manchester.ac.uk; Croxford, W; Fornacon-Wood, I; Wicks, K; Ahmad, S; Britten, A; Carson, C; Dorey, N; Hatton, M; Hiley, C; et al. (2021-10-28)
      In response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I-III lung cancer from April to October 2020. Lung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression. In total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease. The COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes. [Abstract copyright: Copyright © 2021. Published by Elsevier Ltd.]
    • Changes in the Proteome Profile of People Achieving Remission of Type 2 Diabetes after Bariatric Surgery

      Iqbal, Zohaib; email: zohaib@doctors.org.uk; Fachim, Helene A.; email: helene.fachim@manchester.ac.uk; Gibson, J. Martin; email: martin.gibson@manchester.ac.uk; Baricevic-Jones, Ivona; email: ivona.baricevic-jones@manchester.ac.uk; Campbell, Amy E.; email: amy.campbel@manchester.ac.uk; Geary, Bethany; orcid: 0000-0002-5592-5532; email: bethany.geary@manchester.ac.uk; Donn, Rachelle P.; orcid: 0000-0001-6976-9828; email: Rachelle.donn@manchester.ac.uk; Hamarashid, Dashne; email: hamarashiddashne@gmail.com; Syed, Akheel; orcid: 0000-0001-8696-7121; email: akheel.syed@manchester.ac.uk; Whetton, Anthony D.; orcid: 0000-0002-1098-3878; email: tony.whetton@manchester.ac.uk; et al. (MDPI, 2021-08-18)
      Bariatric surgery (BS) results in metabolic pathway recalibration. We have identified potential biomarkers in plasma of people achieving type 2 diabetes mellitus (T2DM) remission after BS. Longitudinal analysis was performed on plasma from 10 individuals following Roux-en-Y gastric bypass (n = 7) or sleeve gastrectomy (n = 3). Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was done on samples taken at 4 months before (baseline) and 6 and 12 months after BS. Four hundred sixty-seven proteins were quantified by SWATH-MS. Principal component analysis resolved samples from distinct time points after selection of key discriminatory proteins: 25 proteins were differentially expressed between baseline and 6 months post-surgery; 39 proteins between baseline and 12 months. Eight proteins (SHBG, TF, PRG4, APOA4, LRG1, HSPA4, EPHX2 and PGLYRP) were significantly different to baseline at both 6 and 12 months post-surgery. The panel of proteins identified as consistently different included peptides related to insulin sensitivity (SHBG increase), systemic inflammation (TF and HSPA4—both decreased) and lipid metabolism (APOA4 decreased). We found significant changes in the proteome for eight proteins at 6- and 12-months post-BS, and several of these are key components in metabolic and inflammatory pathways. These may represent potential biomarkers of remission of T2DM.
    • Characterisation of Aspergillus fumigatus Endocytic Trafficking within Airway Epithelial Cells Using High-Resolution Automated Quantitative Confocal Microscopy

      Ben-Ghazzi, Nagwa; email: nagwaben@gmail.com; Moreno-Velásquez, Sergio; email: s.moreno.velasquez@gmail.com; Seidel, Constanze; email: dr.constanze.seidel@gmail.com; Thomson, Darren; orcid: 0000-0002-4800-7717; email: darren.thomson@manchester.ac.uk; Denning, David W.; email: david.denning@manchester.ac.uk; Read, Nick D.; email: nick.read@manchester.ac.uk; Bowyer, Paul; email: paul.bowyer@manchester.ac.uk; Gago, Sara; orcid: 0000-0002-7027-4598; email: sara.gago-2@manchester.ac.uk (MDPI, 2021-06-07)
      The precise characterization of the mechanisms modulating Aspergillus fumigatus survival within airway epithelial cells has been impaired by the lack of live-cell imaging technologies and user-friendly quantification approaches. Here we described the use of an automated image analysis pipeline to estimate the proportion of A. fumigatus spores taken up by airway epithelial cells, those contained within phagolysosomes or acidified phagosomes, along with the fungal factors contributing to these processes. Coupling the use of fluorescent A. fumigatus strains and fluorescent epithelial probes targeting lysosomes, acidified compartments and cell membrane, we found that both the efficacy of lysosome recruitment to phagosomes and phagosome acidification determines the capacity of airway epithelial cells to contain A. fumigatus growth. Overall, the capability of the airway epithelium to prevent A. fumigatus survival was higher in bronchial epithelial than alveolar epithelial cells. Certain A. fumigatus cell wall mutants influenced phagosome maturation in airway epithelial cells. Taken together, this live-cell 4D imaging approach allows observation and measurement of the very early processes of A. fumigatus interaction within live airway epithelial monolayers.
    • Characterisation of microvessel blood velocity and segment length in the brain using multi-diffusion-time diffusion-weighted MRI

      Scott, Lauren A; orcid: 0000-0002-5423-0042; email: lauren.scott-3@postgrad.manchester.ac.uk; Dickie, Ben R; Rawson, Shelley D; Coutts, Graham; Burnett, Timothy L; Allan, Stuart M; orcid: 0000-0001-9646-4456; Parker, Geoff JM; Parkes, Laura M; orcid: 0000-0001-6488-507X (SAGE Publications, 2020-12-16)
      Multi-diffusion-time diffusion-weighted MRI can probe tissue microstructure, but the method has not been widely applied to the microvasculature. At long diffusion-times, blood flow in capillaries is in the diffusive regime, and signal attenuation is dependent on blood velocity (v) and capillary segment length (l). It is described by the pseudo-diffusion coefficient (D*=vl/6) of intravoxel incoherent motion (IVIM). At shorter diffusion-times, blood flow is in the ballistic regime, and signal attenuation depends on v, and not l. In theory, l could be estimated using D* and v. In this study, we compare the accuracy and repeatability of three approaches to estimating v, and therefore l: the IVIM ballistic model, the velocity autocorrelation model, and the ballistic approximation to the velocity autocorrelation model. Twenty-nine rat datasets from two strains were acquired at 7 T, with b-values between 0 and 1000 smm−2 and diffusion times between 11.6 and 50 ms. Five rats were scanned twice to assess scan-rescan repeatability. Measurements of l were validated using corrosion casting and micro-CT imaging. The ballistic approximation of the velocity autocorrelation model had lowest bias relative to corrosion cast estimates of l, and had highest repeatability.
    • Characterisation of road-dust sediment in urban systems: a review of a global challenge

      Haynes, Haydn M.; Taylor, Kevin G.; email: kevin.taylor@manchester.ac.uk; Rothwell, James; Byrne, Patrick (Springer Berlin Heidelberg, 2020-10-21)
      Abstract: Purpose: The proportion of people living in urbanised areas is predicted to rise to > 65% by 2050, and therefore, more humans than ever will be exposed to urban environmental pollution. Accumulation of organic and inorganic substances on street and road surfaces is a major global challenge requiring scientifically robust methods of establishing risk that inform management strategies. This aim of this contribution is to critically review the global literature on urban road–deposited sediment contamination with a specific focus on variability in sampling and analytical methods. Materials and methods: In order to assess the concentration of contaminants in global road-deposited sediment (RDS), a comprehensive search of published RDS studies was completed. We review methodological approaches used in RDS studies to highlight the variability in datasets as a result of sampling technique, grain size fractionation, geochemical and mineralogical characterisation methods and establishing the influence of local geology on contaminant concentrations. We also consider emerging contaminants in RDS, and we provide a workflow diagram which promotes a standardised sampling and analysis regime that we believe can reduce data variability and promote collaboration when it comes to tackling the important issue of RDS contamination. Results and discussion: Across the literature, Asia (except China) and Africa are underrepresented in RDS studies despite these continents having the largest and fastest growing populations, respectively. The removal of tetraethyl lead from gasoline produced a noticeable decrease in lead concentrations in global RDS, and platinum group element (PGE) concentrations in RDS were consistent with catalytic converter usage. Research into the impact of electric vehicles on non-exhaust emissions suggests other contaminants such as zinc may become more prominent in the future. Most RDS studies consider grain size fractions larger than > 20 μm due to sampling constraints despite RDS < 20 μm being most relevant to human health. The use of chemical extraction methods to establish contaminant geochemistry is popular; however, most extraction procedures are not relevant or specific to minerals identified in RDS through microscopic and spectroscopic investigations. Conclusions: This review highlights considerable variability in sampling and analytical approach which makes it difficult to identify broad global patterns in RDS contamination. To remove this variability from future RDS research, this review suggests a workflow plan which attempts to improve the comparability between RDS studies. Such comparability is crucial in identifying more discrete RDS trends and informing future emission policy.
    • Characterisation of seizure induction methods in

      Mituzaite, Jurga; Petersen, Rasmus; Claridge-Chang, Adam; Baines, Richard A; orcid: 0000-0001-8571-4376; email: richard.baines@manchester.ac.uk (2021-07-30)
      Epilepsy is one of the most common neurological disorders. Around one third of patients do not respond to current medications. This lack of treatment indicates a need for better understanding of the underlying mechanisms and, importantly, the identification of novel targets for drug manipulation. The fruitfly has a fast reproduction time, powerful genetics, and facilitates large sample sizes, making it a strong model of seizure mechanisms. To better understand behavioural and physiological phenotypes across major fly seizure genotypes we systematically measured seizure severity and secondary behavioral phenotypes at both the larval and adult stage. Comparison of several seizure-induction methods; specifically electrical, mechanical and heat-induction, show that larval electroshock is the most effective at inducing seizures across a wide range of seizure-prone mutants tested. Locomotion in adults and larvae was found to be non-predictive of seizure susceptibility. Recording activity in identified larval motor neurons revealed variations in action potential patterns, across different genotypes, but these patterns did not correlate with seizure susceptibility. To conclude, while there is wide variation in mechanical induction, heat induction, and secondary phenotypes, electroshock is the most consistent method of seizure induction across known major seizure genotypes in Epilepsy is a neurological disorder affecting 1 in 130 people globally, with a significant impact on patients, families, and society. Approximately one third of epileptics do not respond to currently available medication. Thus, better insights into underlying disease mechanisms and identification of new drugs are needed. Fruit flies ( ) are a powerful genetic model: a number of single gene mutant flies exhibit seizures, phenotypes that have been shown to respond to established antiepileptic drugs. We compare methods of seizure induction and their utility, to establish which induction method is the most consistent across a range of different seizure-inducing genetic backgrounds. Adopting a common method for seizure analysis in this model will, we predict, speed identification of novel anti-convulsive treatments. [Abstract copyright: Copyright © 2021 Mituzaite et al.]
    • Characteristics of nano-plastics in bottled drinking water.

      Huang, Yihe; Wong, Ka Ki; Li, Wei; Zhao, Haoran; Wang, Tianming; Stanescu, Sorin; Boult, Stephen; van Dongen, Bart; Mativenga, Paul; email: p.mativenga@manchester.ac.uk; Li, Lin; email: lin.li@manchester.ac.uk (2021-09-30)
      Plastic pollution in water is threatening the environment and human health. Previous relevant studies mainly focus on macro and micro plastic pollutions and their characteristics. Little is known about the extent and characteristics of nano-scale plastics in our drinking water systems, mainly due to difficulties in their isolation and analysis. These nano-plastics may pose higher risk to human health than micro-plastics. Here we report the collection and analysis of organic nanoparticles from commercial bottled water of two brands. Novel nano-plastic particle imaging and molecular structure analysis techniques have been applied. The findings show the existence of organic nanoparticles, and a likely source has been identified to be the degradation of plastic water bottles. [Abstract copyright: Copyright © 2021. Published by Elsevier B.V.]
    • Characterization of microwave and terahertz dielectric properties of single crystal La2Ti2O7 along one single direction

      Zhang, Man; orcid: 0000-0002-1094-7279; Tang, Zhiyong; orcid: 0000-0002-1921-6034; Zhang, Hangfeng; Smith, Graham; orcid: 0000-0003-3273-7085; Jiang, Qinghui; Saunders, Theo; orcid: 0000-0003-4250-3071; Yang, Bin; Yan, Haixue; orcid: 0000-0002-4563-1100
      New generation wireless communication systems require characterisations of dielectric permittivity and loss tangent at microwave and terahertz bands. La2Ti2O7 is a candidate material for microwave application. However, all the reported microwave dielectric data are average value from different directions of a single crystal, which could not reflect its anisotropic nature due to the layered crystal structure. Its dielectric properties at the microwave and terahertz bands in a single crystallographic direction have rarely been reported. In this work, a single crystal ferroelectric La2Ti2O7 was prepared by floating zone method and its dielectric properties were characterized from 1 kHz to 1 THz along one single direction. The decrease in dielectric permittivity with increasing frequency is related to dielectric relaxation from radio frequency to microwave then to terahertz band. The capability of characterizing anisotropic dielectric properties of a single crystal in this work opens the feasibility for its microwave and terahertz applications.
    • Characterization of microwave and terahertz dielectric properties of single crystal La2Ti2O7 along one single direction

      Zhang, Man; orcid: 0000-0002-1094-7279; Tang, Zhiyong; orcid: 0000-0002-1921-6034; Zhang, Hangfeng; Smith, Graham; orcid: 0000-0003-3273-7085; Jiang, Qinghui; Saunders, Theo; orcid: 0000-0003-4250-3071; Yang, Bin; Yan, Haixue; orcid: 0000-0002-4563-1100 (Elsevier, 2021-08-27)
      New generation wireless communication systems require characterisations of dielectric permittivity and loss tangent at microwave and terahertz bands. La2Ti2O7 is a candidate material for microwave application. However, all the reported microwave dielectric data are average value from different directions of a single crystal, which could not reflect its anisotropic nature due to the layered crystal structure. Its dielectric properties at the microwave and terahertz bands in a single crystallographic direction have rarely been reported. In this work, a single crystal ferroelectric La2Ti2O7 was prepared by floating zone method and its dielectric properties were characterized from 1 kHz to 1 THz along one single direction. The decrease in dielectric permittivity with increasing frequency is related to dielectric relaxation from radio frequency to microwave then to terahertz band. The capability of characterizing anisotropic dielectric properties of a single crystal in this work opens the feasibility for its microwave and terahertz applications.
    • Characterization on microstructure of interface and failure analysis of SiC fiber reinforced Ti-17 composites under tension load

      Zhao, Wenxia; Ciuca, Octav.; email: octav.ciuca@manchester.ac.uk; Yang, Xiaoguang; Tao, Chunhu; Zhou, Xiaorong; Liu, Changkui (IOP Publishing, 2021-05)
      Abstract: In this study, the ultimate tensile strength of unidirectional SiC-fiber/Ti-17 composites was measured in the as-produced condition at room temperature. Fracture and interfacial reaction zone was characterized by using laser confocal microscopy, field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy. Elemental distribution maps of the interfacial reaction layer and titanium matrix were quantitatively examined by electron probe micro-analyzer (EPMA). Micromechanical properties of SiC fiber and titanium matrix was inspected by Nano-indentation. The Fracture failure mechanisms was show that the key microstructural parameters which dominate damage initiation, damage growth and fracture behavior of the composites were explained in detail.
    • Characterization on microstructure of interface and failure analysis of SiC fiber reinforced Ti-17 composites under tension load

      Zhao, Wenxia; Ciuca, Octav.; email: octav.ciuca@manchester.ac.uk; Yang, Xiaoguang; Tao, Chunhu; Zhou, Xiaorong; Liu, Changkui (IOP Publishing, 2021-05)
      Abstract: In this study, the ultimate tensile strength of unidirectional SiC-fiber/Ti-17 composites was measured in the as-produced condition at room temperature. Fracture and interfacial reaction zone was characterized by using laser confocal microscopy, field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy. Elemental distribution maps of the interfacial reaction layer and titanium matrix were quantitatively examined by electron probe micro-analyzer (EPMA). Micromechanical properties of SiC fiber and titanium matrix was inspected by Nano-indentation. The Fracture failure mechanisms was show that the key microstructural parameters which dominate damage initiation, damage growth and fracture behavior of the composites were explained in detail.