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Does noise pollution influence modal choices? A random forest application
Get PDFThis work investigates the relationship between noise pollution and modal choices exploring and comparing two different urban contexts: Greater London and Brisbane. To achieve this, data on commuting flows by mode of transport and estimated noise pollution have been obtained and combined with measures to characterise the built environment which demonstrated to have an influence on modal choices. Random forest models have shown very good performances in solving classification problems to predict transport modes and allow the exploration of non-linear relationships between the predicted classes and explanatory variables. Two random forest models have been tuned, trained and tested to investigate the association between modal choices and contextual variables, including noise pollution, in Greater London and Brisbane. Results have shown that noise levels play a role in predicting modal choices in Greater London, while the characteristics of the built environment are more relevant when predicting modal choices in Brisbane. Furthermore, we find that walking and cycling, despite being both active travel modes, are influenced by very different factors, with cycling displaying patterns more similar to those characterising driving. Evidence showing the varying relationships between walking and cycling with contextual variables, e.g. noise levels, building and street density, presence of amenities can inform more targeted policies to encourage active travel.</p
Fundus Refraction Offset as a Personalized Biomarker for 12-Year Risk of Retinal Detachment
Get PDFPurpose: The purpose of this study was to investigate the potential of a novel anatomical metric of ametropia—fundus refraction offset (FRO)—in stratifying the risk of retinal detachment (RD) or breaks, beyond the influence of risk factors including spherical equivalent refraction (SER).Methods: Participants from the UK Biobank with no prior history of RD/breaks were analyzed (n = 9320). The onset of RD/breaks over a 12-year follow-up period was determined based on linked healthcare data. A previously trained deep learning model was applied to each fundus photograph to predict SER. FRO was defined as the error in the fundus-predicted SER, with a negative value indicating a relatively myopic-looking fundus. Cox regression was used to examine the association of baseline FRO with RD/breaks—adjusting for baseline SER, baseline age, sex, and cataract surgery during follow-up. In a subgroup of participants (n = 7127) with high-quality optical coherence tomography scans, we additionally adjusted for baseline macular thickness (MT). All analyses initially considered any RD/breaks as the event, followed by rhegmatogenous RD/breaks.Results: The mean (SD) baseline age was 54.8 (8.2) years. Sixty-four participants developed RD/breaks (of any subcategory), with a mean (SD) of 7.0 (3.3) years between baseline and disease onset. A more negative baseline FRO was independently associated with an increased risk of any RD/breaks (adjusted hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.50–0.87, P = 0.003) and rhegmatogenous RD/breaks (HR = 0.61, 95% CI = 0.45–0.82, P = 0.001). Similar independent associations were evident in the subgroup analysis that additionally adjusted for MT.Conclusions: A more negative baseline FRO is associated with a higher risk of developing RD/breaks, even among individuals with similar baseline SER and other risk factors. This demonstrates a potential benefit of shifting towards an anatomic definition of myopia
Loss of FCoV-23 spike domain 0 enhances fusogenicity and entry kinetics
Get PDFThe ability of coronaviruses to recombine and cross species barriers affects human and animal health globally and is a pandemic threat 1,2. FCoV-23 is a recently emerged, highly pathogenic recombinant coronavirus responsible for a widespread outbreak of feline infectious peritonitis. Here we report cryogenic electron microscopy structures of two FCoV-23 spike isoforms that correspond to the in-host loss of domain 0 observed in clinical samples. The loss of domain 0 markedly enhances the fusogenicity and kinetics of entry into cells and possibly enables biotype switching and lethality. We show that FCoV-23 can use several aminopeptidase N orthologues as receptors and reveal the molecular determinants of receptor species tropism, including a glycan that modulates human receptor engagement. We define antigenic relationships among alphacoronaviruses that infect humans and other mammalian species and identify a cross-reactive alphacoronavirus monoclonal antibody that inhibits FCoV-23 entry. Our results pave the way for the development of vaccines and therapeutics that target this highly pathogenic virus.</p
Oxford Classic-defined EMT risk stratification of High Grade Serous Ovarian cancer for guiding treatment decisions
No full textPURPOSEThe association between epithelial to mesenchymal transition in High Grade Serous Ovarian Cancer (HGSOC) and poor prognosis is known. However, molecularly defining a subset of tumours that reproducibly associates with poor prognosis has been an elusive goal in this disease. A molecular signature that can robustly identify patients with poor prognosis and guide treatment decisions, including surgical strategy and targeted therapies, can improve survival rates.EXPERIMENTAL DESIGNWe carried out RNA sequencing of 139 tumour samples (Brescia cohort), an external validation on 362 and 126 patients from the Scottish and Garsed cohort, respectively; and meta-analysis of 1023 tumours to develop clinically useful risk groups. Identification of therapeutic targets was carried out by transcriptomic analyses of FLOW-sorted tumour epithelial cells from fresh tumours and multiplex IF assessment of tissue sections.RESULTSIn this study we have validated the prognostic strength of the OxC-EMT in three independent patient cohorts- Brescia [HR=3.6 (95% CI=1.59-7.97, p=1.99e-03], Scottish [HR=1.71 (95%CI=1.08-2.70), p=2.23e-02] and Garsed [Kruskal-Wallis p = 0.00071]. OxC-based riskstratification of HGSOC could robustly identify poor risk patients with a 5-year median survival for OxC-high risk and OxC-low risk groups of 13% and 50%, respectively (95%CI: 7.1%-23.5% vs. 36.1%-69.3%) in the Brescia cohort. Further analysis of the risk groups suggests that an alternate surgical strategy and a combination therapy involving EMT targeting drugs and immunomodulators could elicit improved clinical response in poor risk patients.CONCLUSIONThis study provides a clinically useful risk stratification strategy for HGSOC as well as targeted treatment options for high-risk patients
Development and evaluation of the first fertility preservation patient decision aid to support boys and young men with cancer:The Cancer, Fertility and Me for Boys and Young Men research protocol
No full textIntroduction Many cancer treatments can result in reduced fertility, impacting survivors’ opportunities for biological parenthood. Fertility preservation (FP) methods for boys and young men, such as cryopreservation of testicular tissue or sperm, offer hope but are currently underused among young male patients with cancer. Despite guidelines recommending early discussion of fertility implications, many newly diagnosed males do not receive FP counselling or referral to fertility services. Male cancer survivors face a higher likelihood of infertility than their peers, yet focused FP decision-making support is lacking. This study aims to address this gap by developing and evaluating the first dedicated patient decision aid (PtDA) for boys and young male patients with cancer aged 11–25 years old, to help them make informed FP decisions before receiving cancer treatment.Methods and analysis The current study follows a multistage process: developing the PtDA, alpha testing for acceptability with former patients, parents and healthcare professionals, and beta testing in clinical settings to ensure effective integration into routine care. Using a combination of interviews and questionnaire data, this research will assess the PtDA’s acceptability and impact on decision-making.Ethics and dissemination This study has been prospectively registered on the Research Registry (10273). Ethics approval has been obtained from Leeds Beckett University and the National Health Service/Health Research Authority before undertaking data collection. The final resource will be disseminated widely and made freely available online via our dedicated Cancer, Fertility and Me website, for use in clinical and research practice
Hydrodynamic Response of Mocean Wave Energy Converter in Extreme Waves
No full textThe design of moored floating wave energy converters (WECs) must take into account extreme responses and mooring line loads in order to ensure their survival and continued wave power generation in the ocean environment. This study focuses on Mocean Energy’s Blue Horizon C1 hinged raft WEC and aims to provide a better understanding of its hydrodynamic characteristics in survival wave conditions. To achieve this, a physical model study was conducted on a Froude scale of 1 in 50 at the FloWave Ocean Energy Research Facility, University of Edinburgh. The experiments involved the use of NewWaves focusing of crest and trough at the model hinge location, as well as long crested irregular waves. Motion responses of the fore and aft bodies of the WEC were measured using a Qualisys camera, and single component load cells were used to measure the forces in the 3-point catenary mooring lines. The hydrodynamic characteristics of the WEC were evaluated in terms of response amplitude operators and non-dimensional mooring line loads. Results indicate that the fore and aft bodies of the WEC exhibit similar motion responses, except for the pitch motion. The aft body has a pitch response 2 to 3 times higher than the fore body. Concerning the moorings, the wave load on the mooring line in line with the wave direction was found to be higher than the other two mooring lines which were arranged at an angle to the wave direction. The results will provide insight into the behaviour of the Mocean device in survival wave conditions and will aid with the determination of appropriate design parameters for optimal performance and survival in the ocean environment.</p
Preventing gambling-related harm among adolescents (PRoGRAM-A): an embedded multi-modal process evaluation in a pilot cluster random control trial
No full textBackground and AimsYoung people’s engagement in gambling can be linked to gambling-related harm. This can cause stress, anxiety, relationship issues, debt, and lost opportunities. There is a lack of independently funded, and evidence-based school-based interventions that seek to prevent and reduce the harms associated with gambling. PRoGRAM-A is one of the first independently research funded interventions to prevent gambling related harm in adolescents. This paper presents findings from an embedded process evaluation of the pilot cluster randomised control trial of PRoGRAM-A, with a specific focus on intervention fidelity, feasibility and acceptability.MethodMulti-modal study design comprised of qualitative focus groups with students (N = 42); and individual interviews with teachers (N = 7), PRoGRAM-A trainers (N = 5), student friends and family (N = 2) and stakeholders (N = 8). Structured Observations of the full cycle of PRoGRAM-A across two intervention schools were also undertaken.ResultsPRoGRAM-A was delivered with a high degree of fidelity (95%) to the training manual. It was also found to be both feasible and acceptable to students, staff and parents. It was appealing to schools as it allowed teachers to address the topic of gambling, which had already been flagged as an issue for some of the schools, but they lacked the skill and capacity to take action. Peer Supporters enjoyed the interactive nature of the training workshop. Parents and carers were supportive of the intervention and stakeholders recognised the growing need for a non-industry funded school-based intervention to raise awareness among students of gambling and gambling-related harm (GRH). Suggested intervention refinements include embedding examples of lived experience to aid students’ engagement with the topic of gambling and GRH. Increasing social skills activities to ensure students are comfortable and confident when initiating conversations and making follow-up sessions more interactive (in-line with the two-day workshop).ConclusionsThis study demonstrated that it is feasible and acceptable to deliver the PRoGRAM-A gambling harm reduction intervention within secondary schools with a high degree of fidelity. Addressing the topic of gambling and GRH within the school curriculum was deemed to be acceptable by all sample groups, including students
A point-of-care diagnostic for drug-induced liver injury using surface-enhanced Raman scattering lateral flow immunoassay
No full textParacetamol overdose (POD) is common, with approximately 100,000 cases attending UK hospitals annually. Timely antidote administration is crucial for patients at risk of developing acute liver failure. A rapid point-of-care (POC) assay is required to identify high-risk patients with fit-for-purpose sensitivity and specificity. Here we show that by measuring a circulating biomarker, cytokeratin-18 (K18), accurate detection of drug-induced liver injury (DILI) is possible. To achieve this, we created an in vitro diagnostic medical device designed to quantitatively detect serum K18, consisting of a Lateral Flow Immunoassay (LFIA) paired with a bespoke handheld Raman Reader (HRR) to produce quantitative surface-enhanced Raman scattering (SERS). The diagnostic was assessed in 2 performance evaluation studies using 199 serum samples from individuals following POD. The device achieves diagnostic accuracy for DILI with a specificity of 94% and sensitivity of 82%. Here we show that SERS-LFIA can rapidly identify patients with DILI, allowing individualised treatment pathways
Transforming trade for vaccine equity: Policy gaps and barriers
No full textThe ongoing Pandemic Agreement negotiations illustrate significant gaps in action required to respond effectively to the lessons of the COVID-19 pandemic and make progress towards public health goals, including Sustainable Development Goals (SDGs). The pandemic revealed vaccine equity as a unifying health need, and international trade as a Commercial Determinant of Health. We explored where policy action could reshape trade relationships, identifying recommendations for vaccine equity within stakeholder literature pertaining to Free Trade Agreements (FTAs). We searched online libraries for stakeholder documents that focused on the interface between FTAs, vaccination, and vaccine equity published between 01/01/2010-31/03/2022. Our analytic framework drew from the rights, regulation, and redistribution (3R) framework, combined with systems analysis, using leverage pointsto categorise recommendations as Technical Mechanisms, Collaborative and Adaptive Mechanisms, or Determinants of Vaccine Equity (DVE). These were then located on a novel systems map to elucidate gaps and actions.No cohesive strategies for change were identified. Technical proposals were reactive, repetitive, and lacked enforcement mechanisms or incentives. There were significant gaps in the articulation of alternative Collaborative Mechanisms to democratise FTA policymaking processes. The underlying DVE and lack of policy coherence were not addressed. These findings are limited by under-representation of low- and middle-income country authorship in the studies, including in ours, reflecting imbalances in international research and policymaking processes. Overall, our research shows how the current trade paradigm has produced and sustained vaccine inequity. We propose potential pathways for action but highlight the importance and urgency of more fundamental change in negotiation and implementation of FTAs. New technologies will be crucial for the global response to emerging, neglected, and non-communicable diseases that are vaccine-preventable or -modifiable. Multilateral organisations must, therefore, prioritise the right to health above FTAs, including through TRIPS waivers on Essential Technologies
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