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Role of Outdoor Air Pollution, Noise Pollution, and Green Exposure on Abdominal Aortic Aneurysm Progression
No full textObjectiveRecent evidence suggests an association between air pollution exposure and abdominal aortic aneurysm (AAA) rupture. It is unclear whether environmental factors also influence the rate at which AAAs grow. This study aimed to determine how environmental factors contribute to aneurysm growth using a prospective cohort study design.MethodsThis study used data from the UK Aneurysm Growth Study (UKAGS), a national cohort of men with AAA representative of the UK population in AAA surveillance. Participant records were linked with environmental exposure data from a validated land use regression model, including nitrogen dioxide (NO2) concentrations (μg/m3), particles with an aerodynamic diameter ResultsEnvironmental data were available for 3 360 (86.0%) participants. Mean follow up ± standard deviation was 5.64 ± 2.47 years. There were no statistically significant associations between NO2, PM2.5, and transport noise pollution with AAA growth in adjusted models, whereas relationships with greenspace measures were inconsistent.ConclusionThe link between environmental factors and AAA growth remains unclear. Potential issues include use of those participating in a screening programme (who may be healthier than the general population and less susceptible to environmental influences). Managing traditional risk factors, especially smoking, remains key to clinical care.</p
Comprehensive Observations of Magnetospheric Particle Acceleration, Sources, and Sinks (COMPASS): A Mission Concept to Explore the Extremes of Jupiter’s Magnetosphere
No full textSince the dawn of the space age in 1957, humanity has achieved the remarkable feat of exploring all the planets in our Solar System with robotic spacecraft. This glimpse into the diversity of space environments that make up our Solar System has revealed that no two planetary systems are identical; however, each planet harbors key clues in working toward a more unified and predictive understanding of the basic structure and dynamics of all planetary, and even exosolar, magnetospheres. A common feature found in all strongly magnetized planets are regions of trapped, high-energy charged particles called radiation belts. Dedicated missions studying the radiation belts encompassing Earth have led to major space physics discoveries over the past several decades, but Earth’s magnetosphere exists in a relatively small swath of the parameter space found in our Solar System. To expand that parameter space, we present a mission concept that was reported in the recent National Academies of Sciences, Engineering, and Medicine (NASEM) Decadal Survey to expand the frontiers of Heliophysics in the 2024-2033 decade. The mission concept is called COMPASS, short for Comprehensive Observations of Magnetospheric Particle Acceleration, Sources, and Sinks. COMPASS is a mission dedicated to the exploration of Jupiter’s radiation belts, with an unprecedented suite of instruments covering i) particle species from thermal plasma to 10 tens of MeV electrons and relativistic protons and heavy ions; ii) comprehensive magnetic and electric fields and waves; and iii) dedicated X-ray imaging. COMPASS will enable the scientific community to test existing hypotheses and make new discoveries of how Jupiter’s radiation belts are sourced, accelerated, and lost within such a complex system.</p
State Immunity and the New York Convention
No full textDoes a state waive its right to sovereign immunity under the State Immunity Act 19781 (“SIA”) and thereby submit to the adjudicative jurisdiction of the English courts because it has ratified the New York Convention on the Recognition and Enforcement of Foreign</p
An Evaluation of the Use of Automated Chatbots Within One Psychological Therapy Service
No full textObjectivesThis study evaluated the effectiveness of the use of automated chatbots within one NHS Talking Therapies provider. Two chatbots were designed and piloted: (1) to help prepare patients for therapy and (2) to provide solution-based coaching to patients regarding a problem or concern. This study aimed to evaluate the effectiveness of the use of these chatbots in the NHS Talking Therapies service.MethodsThe chatbots were made available to patients (N = 4329) who had been referred for therapy and were waiting for their first assessment. Data from a control group of patients (N = 4333) who did not use a chatbot were also analysed. The evaluation adopted a mixed methods approach to capture data relating to the conversations had by patients with the chatbot, feedback regarding satisfaction with its use, data relating to patient attendance and standardised outcome measures relating to patients' improvements in anxiety and depression.ResultsQualitative data showed that the chatbots were received positively by patients who gave feedback. Quantitative data showed non-attendance was significantly lower in the control group (p ≤ 0.001), cancellations were significantly lower in the control group (p ≤ 0.001), but days spent in therapy were significantly higher in the chatbot groups (p ≤ 0.001). All groups saw significant improvements in their GAD-7 (p = 0.000) and PHQ-9 (p = 0.000) scores.ConclusionsIn NHS Talking Therapy services, waiting times have been problematic; thus, chatbots can be a useful tool to assist patient engagement while they wait for their appointment. Therefore, they have the potential to reduce anxiety, frustration or disappointment in patients who are unable to wait for too long and may drop out before they start therapy.ImplicationsThis research shows the potential benefits of using AI chatbots as an additional resource in therapy.This research provides evidence to support the use of AI chatbots in the NHS Talking Therapies service. This is an area of practice that currently has only limited research to support the use of chatbots within it.This research provides a possible solution in the form of an AI chatbot to reduce frustration in service users while they are on a waiting list for therapy.The Five Year Forward View for Mental Health and the NHS Long Term plan were committed to the further expansion of NHS Talking Therapies for anxiety and depression. This research highlights the use of AI chatbots in helping improve retention in the NHS Talking Therapies service while users await their first appointment.</p
Embedding Silver Nanoparticles Uniformly into the Surface Layer of Low-Density Polyethylene and their Effects on Photodegradation
No full textNanomaterials offer a potential solution for the problem of plastic waste by enhancing degradation. So far, their incorporation into plastics has largely relied on ‘blending’ procedures that lead to aggregation, dismissing properties of individual nanoparticles. This project explores AgNPs as a possible photocatalyst to enhance degradation of LDPE. AgNPs are embedded into the surface of the film, where they are monodispersed and uniformly distributed to maximise light absorption. Nanoparticles have greater tendency to aggregate on surfaces and to date, there is no evidence in literature of monodispersed nanoparticles embedded in LDPE.This study establishes a method to embed AgNPs, sized ~5 nm, into the surface layer of LDPE film to investigate their photo-degrative effects under UV radiation. LDPE undergoes photo-degradation by direct cleaving of C−C and C−H bonds. UVC irradiation studies revealed bond scission occurred predominantly at the end chains of the polymer; these results contradict those in literature whereby photodegradation occurs more on the main chain due to the absence of steric hindrance. UVB studies showed that bond scission occurred less at the end chains. This suggests that differences in photon energy may influence photodegradation mechanisms.Furthermore, results showed that one layer of monodisperse AgNPs embedded into the surface layer of LDPE marginally increased the photodegradation rate of LDPE when subjected to UVC light, compared to virgin LDPE. This was observed by a change in the crystallinity content of LDPE. Increasing the number of AgNP layers into the surface of LDPE did not exhibit a greater degree of photodegradation when subjected to UVC light. Given the small fraction of AgNPs incorporated into LDPE (no more than one layer), our research suggests that AgNPs may be an effective additive to LDPE to enhance degradation upon UVC exposure. This pre-treatment method offers potential future development for photo-degradable plastics.</p
Redacted anonymised focus group transcripts from physiotherapists and community providers
No full textAnonymised transcripts for physiotherapist and community provider focus groups discussing sleep, physical activity and sedentary behaviour 'usual care' support for people living with multiple long-term conditions and frailty.</p
Climate change challenges grey wolf resilience: insights from dental microwear
No full textThe grey wolf exemplifies ecological resilience, having survived major climaticfluctuations since the Middle Pleistocene. Once the world’s most widely distributedmammal, its range has been drastically reduced by human-driven habitat loss,persecution, and competition for resources. Although listed as of Least Concernglobally by the IUCN, the omission of climate change as a threat raises criticalquestions about its future persistence. This study examines dietary flexibility inEuropean grey wolves (Canis lupus) using dental microwear texture analysis(DMTA). We compare British Pleistocene wolves from the Last Interglacial (MIS 5e)and the penultimate interglacial (MIS 7a–c) and contemporary wolves from Poland.Results suggest that during periods of elevated global temperatures, wolves exhibitevidence of increased durophagy. These data demonstrate deep-time dietaryplasticity and recurrent behavioural shifts, indicating that while the grey wolf isresilient, future warming winters may significantly reshape wolf diets in the mid-latitude ecosystems.</p
Interacting drivers of Holocene climate change in southwestern Africa: the influence of insolation, rainbelt dynamics and upwelling
No full textUnderstanding regional-scale patterns of long-term climate variability is essential for identifying the drivers of past environmental change. In southern Africa, the continent is often divided into three rainfall zones—summer, winter, and aseasonal—but this framework fails to capture the finer dynamics of transitional areas where tropical, subtropical, and temperate systems converge. This study examines Holocene climate variability along the western margin of the southern African monsoon region using a new 7300-year nitrogen isotope record from rock hyrax middens at Omanyne-4 in northern Namibia. Unlike other Namib Desert records that indicate progressive aridification through the Holocene, the Omanyne-4 sequence shows a long-term trend toward increasing humidity, consistent with insolation-driven enhancement of tropical and Indian Ocean moisture advection. Comparisons with records from northern Namibia, Botswana, and western Zambia reveal a coherent pattern of mid-to late Holocene humidification across the northwestern interior, in contrast to coastal aridification. Periods of both in-phase and antiphase variability with other regional records highlight the role of the Angola–Benguela Front and associated upwelling dynamics in modulating Namibian hydroclimate. These results delineate distinct Holocene climate response regions in northern Namibia and Botswana and demonstrate the non-linear nature of regional responses to insolation forcing and underscore the importance of coastal–inland atmospheric interactions in shaping long-term hydroclimate variability in southwestern Africa.</p
Establishing Reference Intervals And Developing A Functional Lc-Ms/Ms Assay For Aspirin And Metabolites
No full textAspirin is one of the oldest, and most commonly used drugs. Low dose aspirin (75 mg) is recommended as an antiplatelet agent for secondary prevention in cardiovascular disease (CVD), and in high-risk pregnancies for the prevention of pre-eclampsia (PE). Aspirin prevents platelet aggregation by inhibiting the cyclooxygenase (COX-1) enzyme at low doses through acetylation of a serine amino acid, thus blocking the production of downstream prostaglandins including thromboxane A2 (TXA2). Aspirin is rapidly metabolised to salicylic acid (SA) and subsequently to conjugated glucuronides and glycine derivatives. There is significant inter-individual variation in aspirin metabolism depending on sex, ethnicity, and diet. Additionally, studies have reported that up to 65% of the population are categorised as aspirin resistant due to suboptimal platelet inhibition. Previous studies have also shown that up to 30% of patients are non-adherent to their medications using chemical adherence testing (CAT). Yet there are a lack of studies which have reported on non-adherence to aspirin in the general population using CAT due to the absence of reference intervals (RIs). RIs for aspirin metabolites in the blood are required for interpretation of CAT results as these metabolites are also derived from dietary intake. Therefore, baseline levels need to be determined for the purpose of distinguishing between dietary salicylates and salicylate metabolites of aspirin. Moreover, current assays for functional testing of aspirin are burdened by poor reproducibility. Therefore, new robust assays which test for adequate inhibition of the COX-1 enzyme by aspirin are required.The aim of this thesis was to use liquid chromatography tandem mass spectrometry (LC-MS/MS) to develop an assay to quantify levels of major metabolites of aspirin including salicylic acid (SA) in plasma. The assay was analytically validated according to the American National Standards Institute-American Standards Board (ANSI-ASB) guidelines. Calibration curves, bias, and precision met the acceptable criteria for all metabolites bar aspirin.RIs required for interpreting the levels found in patients were established in two cohorts. The first cohort was from the study titled “Evaluation of Trimethylamine-N-oxide (TMAO) levels as a risk factor for coronary artery disease (CAD) in South Asians vs. Caucasians” containing a nearly equal number of females and males in addition to Caucasian and South Asian individuals with CAD. The second cohort was the Pre-Eclampsia And Chronic Hypertension, rEnal and SLE (PEACHES) cohort, consisting of pregnant women at high risk of developing PE. The 97.5th percentiles were higher in females within the TMAO cohort compared to the males (97.5th centile being 8481 ng/mL in females compared to 7651 ng/mL in males prescribed aspirin). Additionally, non-pregnant females had significantly higher levels than pregnant females when the TMAO percentiles were compared with the PEACHES percentiles. The 97.5th centile in the TMAO cohort females prescribed aspirin was 8481 ng/mL compared to 458 ng/mL in those prescribed aspirin in the PEACHES cohort (pThe final aim of this thesis was to develop a functional assay to assess aspirin inhibition of the COX-1 enzyme. The target peptide was detected using digested recombinant COX-1 protein. Although the target peptide was not detectable in non-fortified human matrix, the work conducted has established knowledge of key practical limitations in detectability. This will inform future work and projects planned to target membrane proteins.</p
Investigating the impact of multiallelic copy number variation on disease-relevant traits in UK and African populations
No full textThe contribution of multiallelic CNVs (mCNVs) to disease risk has not been widely studied, as they have been difficult to characterise at large-scale genome-wide, and are often not strongly associated with flanking SNPs. Previous work in this area frequently comes to conflicting conclusions. Improved understanding of the role of mCNVs in disease risk could lead to novel insights into the pathobiology of disease.I used ClinCNV to robustly type 69 mCNVs from UK Biobank whole exome sequences in discovery (n=152,853) and replication sets (n=269,317). Discovery and replication PheWAS of these variants used the DeepPheWAS R package, which interrogates clinically-curated composite phenotypes by integrating self-report, primary and secondary health care data. Unrelated participants of African (AFR), European (EUR) and Central/South Asian (CSA) ancestry were included in this analysis.In total, 173 significant mCNV-phenotype associations were detected from 26 mCNVs (FDR Statistically significant correlation of mCNV copy number with gene expression or protein level was detected in 33% of gene expression corelations and 80% of protein correlations. While predicted copy number generally had a weak effect on gene expression and protein levels (correlation < 0.3), 25% of gene expression and 30% of protein level correlations were moderate to strong. These findings support the biological relevance of mCNVs, which may underlie phenotype mechanisms. Accurate typing and large sample sizes are necessary to reveal genetic associations of mCNVs, and this work provides several novel likely causative variants contributing to clinically-important traits.</p