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Improving the assessment of risk factors relevant to potential carcinogenicity of gene therapies: a consensus paper
Get PDFSupplementary Material is available online at: https://www.liebertpub.com/doi/full/10.1089/hum.2024.033#supplementary-materials .M.T. is a cofounder and Director of TestAVec Ltd., spun-out from Brunel University, and holds a patent concerning hInGetox “Method for Testing a Gene Therapy Vector” IP number PCT/GB2018/051937 with several collaborative projects in safety for gene therapy.Regulators and industry are actively seeking improvements and alternatives to current models and approaches to evaluate potential carcinogenicity of gene therapies (GTs). A meeting of invited experts was organised by NC3Rs/UKEMS (London, March 2023) to discuss this topic. This paper describes the consensus reached amongst delegates on the definition of vector genotoxicity, sources of uncertainty, suitable toxicological endpoints for genotoxic assessment of GTs, and future research needs. The collected recommendations should inform the further development of regulatory guidelines for the non-clinical toxicological assessment of GT products.This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The UK NC3Rs supported attendance costs for EU and UK-based academic attendees and UKEMS provided bursaries for a number of the workshop attendees. NC3Rs hosted the workshop in London, March 2023
Editorial: The role of education in raising awareness towards antimicrobial resistance (AMR)
Get PDFEditorial on the Research Topic: The Role of Education in Raising Awareness Towards Antimicrobial Resistance.Antimicrobial resistance (AMR) poses a significant threat to global health, requiring multifaceted strategies to mitigate its spread. Education plays a pivotal role in raising awareness and providing various stakeholders with the knowledge and skills to address various AMR issues. This editorial summarizes the contributions published in the Research Topic “The role of education in raising awareness towards antimicrobial resistance” featuring innovative educational strategies and their impact on AMR awareness and stewardship
Interactions of CaO with pure Mg and Mg-Ca alloys—an in situ synchrotron radiation diffraction study
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The data cannot be made publicly available upon publication because no suitable repository exists for hosting data in this field of study. The data that support the findings of this study are available upon reasonable request from the authors.CaO additions are used as an inexpensive replacement for Ca in Mg alloys. CaO dissociation in Mg has been reported in literature without a clear mechanism as to why this occurs. In situ synchrotron radiation diffraction investigation of the melting and solidification of Mg with CaO shows, that the stability of CaO was overestimated in Mg melts compared with MgO. The experiments that were performed on the Mg-20CaO and Mg-xCa-6CaO (x = 6 and 16 wt.%) alloys, show the dissociation and formation of various phases during melting and solidification. The results indicate that Mg can reduce CaO even in the solid state, which is the opposite of that proposed by the Ellingham diagrams for stoichiometric reaction. Phase formations during the in situ experiment are compared with published thermodynamic calculations for the interaction between Mg-Ca alloys and oxides.The authors acknowledge the Deutsches Elektronen-Synchrotron (DESY) in Hamburg, Germany, for the provision of synchrotron radiation facilities within the framework of the proposal I-20130330 and the Federal Ministry for Economic Affairs and Energy (BMWi) for funding the project MagHyM (20K1107B)
Research and development of combustion engines with sustainable and zero-carbon fuels
Get PDFThis thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonAs governments worldwide address the increasing levels of CO2 emissions, the automotive industry faces a significant challenge in mitigating climate change. To this end, the industry is exploring various solutions, including electrification and battery electric vehicles, as well as the adoption of low-carbon and zero-carbon fuels in Internal Combustion (IC) engines.
While the electrification of vehicles has grown in popularity, it has challenges, such as the high cost of batteries, limited driving range, and the need for charging infrastructure. In light of this, there is also growing interest in using low-carbon and zero-carbon fuels, such as biofuels, hydrogen, and synthetic fuels, in IC engines.
These fuels represent a promising approach to achieving net zero-carbon transportation and reducing the industry’s carbon footprint. Biofuels, for example, can be produced from renewable sources and significantly reduce greenhouse gas emissions compared to conventional fossil fuels. Hydrogen, meanwhile, can power internal combustion engines with zero emissions when produced using renewable energy sources. Synthetic fuels, produced with renewable energy, provide a more sustainable alternative to traditional fossil fuels.
Adopting low-carbon and zero-carbon fuels in IC engines offers an effective and accessible pathway towards a more sustainable future. While electrification gains momentum, using sustainable fuels in IC engines provides a promising approach to achieving net zero-carbon transportation and reducing the industry’s carbon footprint.
The present study confidently investigates two key solutions for accomplishing net-zero targets. Firstly, it explores the feasibility of second-generation biofuels with varying ethanol and Research Octan numbers as immediate drop-in replacements for fossil fuels. The study meticulously examines injection strategies for mitigating particulate matter emissions associated with these fuels.
The study revealed that biogasoline fuel from 2nd generation feedstock could be used seamlessly in existing spark ignition engines without hardware modifications. This research emphasizes the significance of biofuels in attaining a zero-carbon future. Nevertheless, it is crucial to ensure sustainable biofuel production to offer low-carbon alternatives to conventional fossil fuels while considering land use, water consumption, and biodiversity conservation. The research findings provide strong evidence that biogasoline, due to its heavier components, is more likely to generate higher levels of PM emissions. However, it has been proven that deploying the right split injection methods can significantly minimise PM emissions.
Secondly, the study focuses on hydrogen as the primary power source for ICE platforms. Through a comprehensive analysis of various injection methods and proportions, the study showcases the full potential of hydrogen as a substitute for gasoline. Additionally, the study confidently addresses performance and emission concerns by investigating NOx and CO2/Hc emissions associated with lubricants, using a novel method to identify the potential of considering H2ICE as a zero-carbon solution. The findings of this study are expected to confidently contribute to achieving net-zero targets. Hydrogen fuel has many advantages, such as running engines efficiently in lean conditions and maintaining stable combustion while achieving up to lambda 3.8. This translates to higher thermal efficiency, lower cyclic variability, and zero NOx emissions. Additionally, hydrogen combustion is an eco-friendly source of fuel, emitting no HC, CO, and CO2. Even under low load, exhaust hydrogen slip remains below 1000 ppm, which drops below 500 ppm with increased load. These remarkable results suggest that hydrogen would be an ideal fuel to replace gasoline and natural gas in a spark ignition engine with superior efficiency, zero emissions and greater engine performance. The study found that centrally-mounted (CDI) and side-mounted direct injection (SDI) direct injection systems had zero CO2, CO, and HC emissions during the steady state operations. The CDI and SDI setups demonstrated stable engine operations over a broad range of air-to-fuel ratios, with CDI having a more extensive range of lean-burn operations. CDI also had notably higher thermal efficiencies than SDI. The study identified the optimal operational settings for each system. It showed that CDI and SDI had similar emissions characteristics at low and mid-load, with SDI producing higher NOx and hydrogen emissions than CDI. After analysing NOx and lubricant emissions, it has been determined that NOx emissions are nearly non-existent within the lambda range of 2.75 to 3.7.
Furthermore, it has been discovered that hydrogen emits 13.8% less NOx emissions than gasoline during stoichiometric operation. Lastly, the comprehensive NOx time analysis indicates that hydrogen exhibits greater consistency in NOx emissions than gasoline. The CO2/HC averaged emissions are nearly zero, while the peak spikes are less than 18 ppm
Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease
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This is an open access article under the CC BY 4.0 license.
The PHOSP-COVID protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online at ref. 76. Access to these materials can be granted by contacting [email protected] and [email protected].
The ISARIC4C protocol, data sharing and publication policy are available at https://isaric4c.net. ISARIC4C’s Independent Data and Material Access Committee welcomes applications for access to data and materials (https://isaric4c.net).
The datasets used in the study contain extensive clinical information at an individual level that prevent them from being deposited in an public depository due to data protection policies of the study. Study data can only be accessed via the ODAP, a protected research environment. All data used in this study are available within ODAP and accessible under reasonable request. Data access criteria and information about how to request access is available online at ref. 76. If criteria are met and a request is made, access can be gained by signing the eDRIS user agreement.Code availability:
Code was written within the ODAP, using R v4.2.0 and publicly available packages (‘data.table v1.14.2’, ‘EnvStats v2.7.0’, ‘tidyverse v1.3.2’, ‘lme4 v1.1-32’, ‘caret v6.0-93’, ‘glmnet v4.1-6’, ‘mdatools v0.14.0’, ‘ggpubbr v0.4.0’, ‘ggplot2 v3.3.6’, ‘bootnet v1.5.6’ and ‘qgraph v1.9.8’ packages). No new algorithms or functions were created and code used in-built functions in listed packages available on CRAN. The code used to generate data and to analyze data is publicly available at https://github.com/isaric4c/wiki/wiki/ISARIC; https://github.com/SurgicalInformatics/cocin_cc and https://github.com/ClaudiaEfstath/PHOSP_Olink_NatImm.One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.This research used data assets made available by ODAP as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref. MC_PC_20058). This work is supported by the following grants: the PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research (NIHR; grant references MR/V027859/1 and COV0319). ISARIC4C is supported by grants from the National Institute for Health and Care Research (award CO-CIN-01) and the MRC (grant MC_PC_19059) Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research (grant reference C18616/A25153). Other grants that have supported this work include the UK Coronavirus Immunology Consortium (funder reference 1257927), the Imperial Biomedical Research Centre (NIHR Imperial BRC, grant IS-BRC-1215-20013), the Health Protection Research Unit in Respiratory Infections at Imperial College London and NIHR Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England, (NIHR award 200907), Wellcome Trust and Department for International Development (215091/Z/18/Z), Health Data Research UK (grant code 2021.0155), MRC (grant code MC_UU_12014/12) and NIHR Clinical Research Network for providing infrastructure support for this research. We also acknowledge the support of the MRC EMINENT Network (MR/R502121/1), which is cofunded by GSK, the Comprehensive Local Research Networks, the MRC HIC-Vac network (MR/R005982/1) and the RSV Consortium in Europe Horizon 2020 Framework Grant 116019. F.L. is supported by an MRC clinical training fellowship (award MR/W000970/1). C.E. is funded by NIHR (grant P91258-4). L.-P.H. is supported by Oxford NIHR Biomedical Research Centre. A.A.R.T. is supported by a British Heart Foundation (BHF) Intermediate Clinical Fellowship (FS/18/13/33281). S.L.R.-J. receives support from UK Research and Innovation (UKRI), Global Challenges Research Fund (GCRF), Rosetrees Trust, British HIV association (BHIVA), European & Developing Countries Clinical Trials Partnership (EDCTP) and Globvac. J.D.C. has grants from AstraZeneca, Boehringer Ingelheim, GSK, Gilead Sciences, Grifols, Novartis and Insmed. R.A.E. holds a NIHR Clinician Scientist Fellowship (CS-2016-16-020). A. Horsley is currently supported by UK Research and Innovation, NIHR and NIHR Manchester BRC. B.R. receives support from BHF Oxford Centre of Research Excellence, NIHR Oxford BRC and MRC. D.G.W. is supported by an NIHR Advanced Fellowship. A. Ho has received support from MRC and for the Coronavirus Immunology Consortium (MR/V028448/1). L.T. is supported by the US Food and Drug Administration Medical Countermeasures Initiative contract 75F40120C00085 and the National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections (NIHR200907) at the University of Liverpool in partnership with UK Health Security Agency (UK-HSA), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. L.V.W. has received support from UKRI, GSK/Asthma and Lung UK and NIHR for this study. M.G.S. has received support from NIHR UK, MRC UK and Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool. J.K.B. is supported by the Wellcome Trust (223164/Z/21/Z) and UKRI (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1 and MC_PC_20029). The funders were not involved in the study design, interpretation of data or writing of this manuscript. The views expressed are those of the authors and not necessarily those of the Department of Health and Social Care (DHSC), the Department for International Development (DID), NIHR, MRC, the Wellcome Trust, UK-HSA, the National Health Service or the Department of Health. P.J.M.O. is supported by a NIHR Senior Investigator Award (award 201385). We thank all the participants and their families. We thank the many research administrators, health-care and social-care professionals who contributed to setting up and delivering the PHOSP-COVID study at all of the 65 NHS trusts/health boards and 25 research institutions across the United Kingdom, as well as those who contributed to setting up and delivering the ISARIC4C study at 305 NHS trusts/health boards. We also thank all the supporting staff at the NIHR Clinical Research Network, Health Research Authority, Research Ethics Committee, Department of Health and Social Care, Public Health Scotland and Public Health England. We thank K. Holmes at the NIHR Office for Clinical Research Infrastructure for her support in coordinating the charities group. The PHOSP-COVID industry framework was formed to provide advice and support in commercial discussions, and we thank the Association of the British Pharmaceutical Industry as well the NIHR Office for Clinical Research Infrastructure for coordinating this. We are very grateful to all the charities that have provided insight to the study: Action Pulmonary Fibrosis, Alzheimer’s Research UK, Asthma and Lung UK, British Heart Foundation, Diabetes UK, Cystic Fibrosis Trust, Kidney Research UK, MQ Mental Health, Muscular Dystrophy UK, Stroke Association Blood Cancer UK, McPin Foundations and Versus Arthritis. We thank the NIHR Leicester Biomedical Research Centre patient and public involvement group and Long Covid Support. We also thank G. Khandaker and D. C. Newcomb who provided valuable feedback on this work. Extended Data Fig. 10 was created using Biorender
Researching the Everyday Educational Lives of Low-Income Families: The Importance of Researcher and Participant Contexts
Get PDFThis paper highlights the importance of considering both researcher and participant contexts when exploring everyday educational lives. It emerges during a period of increasing and sustained social inequality in England, and against a backdrop of increasingly tight research timeframes and resources in higher education. Drawing on a project engaging low-income families in Greater London, the paper takes the everyday as its conceptual focus and questions how we can be critically attentive to everyday educational lives if we struggle to access and develop research relationships with particular social groups. We offer empirical insight into the hesitancies towards, and avoidances of, research participation that centre around knowledge, fear, and trust, and which are heightened concerns where aspects of family life, parenting, and children come to the fore. The paper considers how these can be mitigated in an academic environment where limited time and resourcing shape possibilities of research engagements and offers practical moves linked to research relationships, relevance and presence for how researchers can address these challenges to enable research to be more inclusive.Brunel University London - Grant number 12224104, funded by the Institute of Communities and Societies, Brunel University London, 2022 was awarded to authors 1,2, 4–6. Author 3 was the project’s research assistant.
Experimental and Numerical Investigation of the Use of Ultrasonic Waves to Assist Laser Welding
Get PDFData Availability Statement: Data are contained within the article.This study evaluates the enhancement of laser welding using ultrasonic waves aimed at reorganising the intermetallic position in such a fashion that leads to increased mechanical properties of welds in battery pack assemblies for electric vehicles. The experiment employed 20 kHz and 40 kHz High-Power Ultrasound Transducers (HPUTs) in both contact and contactless modes. A simplified experimental configuration is suggested to represent conditions similar to those found in electric vehicle battery pack assemblies. Measurements of vibration transmission to aluminium alloy 1050 plates revealed more than a 1000-fold increase in acceleration amplitude in contact mode compared to contactless mode. The 20 kHz transducer in contactless mode demonstrated superior performance, showing a 10% increase in load and 27% increase in extension compared to welding without ultrasonic assistance. On the other hand, the 40 kHz transducer, while still improved over non-ultrasonic methods, showed less pronounced benefits. This suggests that lower-frequency ultrasonic assistance (20 kHz) is more effective in this specific context. The study explores ultrasonic assistance in laser welding copper (Cu101) to aluminium alloy 1050 using 20 kHz and 40 kHz HPUTs, showing that both transducers enhance microstructural integrity by reducing copper homogenisation into aluminium, with the 20 kHz frequency proving more effective in this context. A numerical simulation was conducted to evaluate the transmission of pressure into the molten pool of the weld, correlated with the vibration results obtained from the 20 kHz transducer. The numerical simulation confirms that no cavitation is initiated in the molten pool area, and all improvements are solely due to the ultrasonic waves.This research was funded by Innovate UK, grant number: 10018077. The APC was funded by Brunel University London
Description of the constitutive behaviour of stainless steel reinforcement
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Data will be made available on request.This paper presents a comprehensive analysis of the constitutive relationship of stainless steel reinforcement and proposes new material models for both austenitic and duplex stainless steel bars. These are an advancement on existing models which have largely been developed for structural stainless steel plate, rather than for reinforcement bars. Current design guidance for material modelling of reinforcing bars does not include representative stress-strain relationships which capture the unique mechanical properties of stainless steel reinforcement. Codes include idealised elastic-plastic material models which are inappropriate and inefficient for the highly nonlinear and ductile material response of stainless steel. The present study aims to address this issue by first conducting a series of tensile tests to ascertain the stress-strain material responses and then employing this data to examine the validity of existing approaches and propose new material models where required. It is shown that new material models are required and those that are developed are able to accurately capture the stress-strain response of stainless steel reinforcement, and provide a better, more accurate, representation than existing methods
Consumer Protection in the UK Energy Sector
No full textPublished September 27, 2024 by Routledge (https://www.routledge.com/Routledge-Handbook-of-Consumer-Protection-and-Behaviour-in-Energy-Markets/Hunter-Krasniewski-Malinauskaite-Czarnecka/p/book/9781032452012, pp. 81 - 93).The UK energy policy is designed based on the so-called ‘energy trilemma’ consisting of sustainability, security and affordability. This chapter will predominantly focus on affordability, minimisation of the cost of energy to consumers, and other measures implemented in the UK to support consumers. Due to high wholesale energy prices, mainly driven by rising international gas prices, have swelled significant pressure on consumer energy bills making the cost of living a real challenge, especially for vulnerable consumers. Specifically, this chapter will discuss price caps on the cost per unit of energy that are currently in force. It will also review other support measures available to ensure that consumers in vulnerable situations are treated fairly. The chapter will also cover historical development of the UK energy sector, consumer protection, consumer rights in the energy sector and finally, the most recent Government initiatives
Evidence for tWZ production in proton-proton collisions at = 13 TeV in multilepton final states
Get PDFData availability: Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the
CMS data preservation, re-use and open access policy (https://cms-docdb.cern.ch/cgi-bin/PublicDocDB/RetrieveFile?docid=6032&filename=CMSDataPolicyV1.2.pdf&version=2).A preprint version if the article is available at: arXiv:2312.11668v2 [hep-ex], https://arxiv.org/abs/2312.11668v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/TOP-22-008 (CMS Public Pages). Report number: CMS-TOP-22-008, CERN-EP-2023-146.The first evidence for the standard model production of a top quark in association with a W boson and a Z boson is reported. The measurement is performed in multilepton final states, where the Z boson is reconstructed via its decays to electron or muon pairs and the W boson decays either to leptons or hadrons. The analysed data were recorded by the CMS experiment at the CERN LHC in 2016-2018 in proton-proton collisions at s√ = 13 TeV, and correspond to an integrated luminosity of 138 fb^−1. The measured cross section is 354 ± 54 (stat) ± 95 (syst) fb, and corresponds to a statistical significance of 3.4 standard deviations.SCOAP
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