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Introduction to the special issue collection, How and why are health inequalities changing over time?
Get PDF•Health inequalities remain persistent and durable, yet how and why they change over time is less known and examined.•This Special Issue brings together 16 studies examining trends in health inequalities across 20+ countries, including many outside the Global North.•While overall health outcomes improved over time in many studies, inequalities often persisted.•As such, concerted efforts are required to reduce health inequalities specifically, by addressing inequalities in the underlying macrosocial drivers of health
Defined roles for the Staphylococcus aureus POT transporter DtpT in di/tripeptide uptake and glutathione utilisation inside human macrophages
Get PDFPeptides available in biological niches inhabited by the human pathogen Staphylococcus aureus serve as a rich source of amino acids required for growth and successful host colonisation. Uptake of peptides by S. aureus involves at least two transport systems: the di/tripeptide permease DtpT and the oligopeptide ABC transporter Opp3. Here we study the individual and combined functions of DtpT and Opp3 in enabling utilisation of diverse di-/tripeptides via a high-throughput phenotypic screen. We reveal that DtpT is the primary route of uptake for dipeptides, and although many peptides can be utilised via either of the two transport systems, we demonstrate a clear preference for Asp/Glu-containing peptides among DtpT substrates. To better understand the substrate preferences of DtpT, the protein was purified and reconstituted into proteoliposomes. Active transport of diverse di- and tripeptides was demonstrated, supporting the conclusions of the phenotypic screen. During this in vitro analysis, we discovered that DtpT could transport the biologically prevalent tripeptide glutathione (GSH). Bacterial growth assays demonstrate that dtpT is essential for GSH utilisation in the absence of the known glutathione transporter, Gis, identifying DtpT as the second GSH uptake system of S. aureus. We demonstrate that GSH transport is required by S. aureus for complete fitness during in vitro macrophage infection experiments. Finally, based on analysis of the DtpT structure and identification of key residues needed for GSH binding and transport, we suggest that GSH transport may be conserved in the DtpT orthologue of Listeria monocytogenes. Together, these data reveal important new functions for DtpT in the utilisation of diverse peptides and point toward a novel role for DtpT (and, potentially, other bacterial POT proteins) in glutathione acquisition during intracellular infection
Healthy eating interventions conducted in small, local restaurants and hot food takeaways: a systematic review
Get PDFObjective: This systematic review investigates the characteristics, effectiveness and acceptability of interventions to encourage healthier eating in small, independent restaurants and takeaways.
Design: We searched five databases (CENTRAL, MEDLINE, Embase, CINAHL and Science Citation Index and Social Science Citation Index) in June 2022. Eligible studies had to measure changes in sales, availability, nutritional quality, portion sizes or dietary intake of interventions targeting customer behaviour or restaurant environments. We evaluated study quality using the Mixed Methods Appraisal Tool. Results are synthesised narratively, and interventions’ impact on personal autonomy is assessed using the Nuffield intervention ladder.
Setting: Small, independent or local restaurants or hot food takeaway outlets, with no restrictions by year or country.
Participants: Anyone selling or purchasing food in intervention settings (e.g. restaurant staff/owners, customers).
Results: We screened 4624 records and included 12 studies describing 13 interventions in 351 businesses. Most studies were of poor quality. Customer-level intervention components mostly operated on the lower rungs of the Nuffield ladder, and most had limited positive effects on increasing demand, measured as sales or orders of healthy options. Whilst rare, most interventions measuring business outcomes operated on higher ladder rungs and showed small positive results. There was insufficient evidence to investigate differences in impact by intervention intrusiveness. Acceptability was greater for interventions that were low-effort, inexpensive and perceived as not negatively impacting on customer satisfaction.
Conclusions: Despite some evidence of small positive effects of healthy eating interventions on healthier purchases or restaurant/hot food takeaway practices, a weak evidence base hinders robust inference
Reward-related activation of fronto-striatal regions scaled negatively with C-reactive protein
Get PDFBackground: Depression is characterized by divergent changes in positive and negative affect. Emerging roles of inflammation in depression portend avenues for novel immunomodulator-based monotherapy, targeting mechanistically distinct symptoms such as anhedonia and pessimism. Methods: To investigate links between these divergent affective components and inflammation, we used a probabilistic reinforcement-learning fMRI paradigm, testing for evidence of hyposensitivity to reward, and hypersensitivity to punishment in low-inflammation depression cases (loCRP depression; CRP ≤ 3 mg/L; N = 48), high-inflammation depression cases (hiCRP depression; CRP > 3 mg/L; N = 31), and healthy controls (HC; CRP ≤ 3 mg/L; N = 45). We aimed to (i) determine whether depression cases with high and low inflammation showed aberrant neural activation to monetary gains and losses compared to controls, and (ii) examine if these alterations correlated with a continuous measure of C-reactive protein (CRP) in depression, as well as indices of anhedonia and pessimism derived from behavioral instruments in depression. Results: Voxel-wise activation was observed in key brain regions sensitive to monetary reward (ventromedial prefrontal cortex, vmPFC; nucleus accumbens, NAc) and punishment (insula) outcomes across all three groups. However, there was no significant difference in activation between groups. Within depression cases, increasing CRP scaled negatively with activation in the right vmPFC and left NAc but not insula cortex. However, there was no significant association between regional activation and severity of anhedonia or pessimism. Conclusions: Our results support the previously reported association between CRP and striatal reward reactivity in depression but do not extend this to processing of negatively valenced information
Memory, trauma, mythistory: the enduring legacy of the French Revolution in French prose fictions, 1789-1853
Get PDFThe following thesis explores the literary representation and memorialization of the French Revolution, primarily in prose fiction, from 1789 to approximately 1850. I consider how the works in question contribute to the development of a broad revolutionary memory, towards what might be described as a national myth. Engaging with theoretical frameworks developed by scholars such as Pierre Nora, Jacques Le Goff, and Hayden White, among others, my study examines the function of revolutionary memory, arguing that the works I discuss reimagine, memorialize, and ultimately mythologize the Revolution. The thesis examines the representational methods and ideological underpinnings of key authors, beginning with counterrevolutionary and ‘eyewitness’ literary accounts by writers such as Joseph de Maistre, Nicolas-Edmé Rétif de la Bretonne, and Louis-Sébastien Mercier. It then moves through epistolary fiction and early Romanticism (Germaine de Staël, Sénac de Meilhan, Chateaubriand), Romantic historicism, and into the mid-century realist and national-historical mythologies of Balzac and Michelet, respectively. A recurring motif is the tension between personal experience, historical record, and imaginative reconstruction—a tension that becomes central to the literary memory of the Revolution. Rather than treating these texts as isolated responses, my thesis argues for a more unified approach, emphasizing the Revolution’s pervasive symbolic presence across genres and decades. It ultimately suggests that the French Revolution became a foundational site of literary production, shaping the imaginative possibilities of fiction and history alike. In doing so, the study reconsiders the ways literary texts served as loci of national memory, trauma, and identity formation in post-revolutionary France
Failure to account for psychiatric symptoms: implications for the replicability and generalisability of psychological science?
No full textBackground: One of the challenges of psychological research is obtaining a sample representative of the general population. One largely overlooked participant characteristic is sub-clinical levels of psychiatric symptoms.
Methods: A series of studies were conducted to assess i) whether typical psychology study participants had more psychiatric symptoms than the general population, ii) whether there are sub-groups defined by psychiatric symptoms within the no-diagnosis, no-medication participant pool, and iii) whether sub-clinical levels of psychiatric symptoms have an effect on standard behavioural tasks. Five UK national datasets (N > 10,000) were compared to data from psychology study participants (Study 1: n = 872; Study 2: n = 43,094; Study 3: n = 267). Results: Psychology study participants showed significantly higher levels of anxiety and depression, and lower well-being, according to four commonly used mental health measures (GHQ-12, PHQ-8, WEMWBS, WHO-5). Five sub-groups within the psychology study participant group were identified based on symptom levels, ranging from none to significant psychiatric symptoms. These groupings predicted performance on tests of executive function, including the Stroop task, and the n-back task, as well as measures of intelligence.
Conclusions: This study demonstrates that standard psychology participant pools are unrepresentative, and suggests that a failure to account for psychiatric symptoms when recruiting for any psychological study is likely to negatively impact the reproducibility and generalisability of psychological science
Quantifying the regional to global climate impacts of individual fossil fuel projects to inform decision-making
Get PDFEvery additional tonne of carbon dioxide emissions adds to global warming1. This means that decisions to approve new fossil fuel projects represent pivotal moments in shaping Earth’s future climate trajectory. Yet, the specific additional global warming caused by project-level CO2 emissions, and the impacts of that warming, are rarely incorporated into decision-making on the acceptability of new fossil fuel projects. Here, we show how quantifying this additional warming enables concrete, foreseeable consequences to be identified and evaluated in a formal risk assessment framework. This approach reveals that major socioeconomic and environmental consequences can be attributed to CO2 emissions associated with individual fossil fuel projects, contrary to the pervasive unquantified claims of negligible risks by project proponents. Furthermore, as countries pursue rapid decarbonisation aligned to their Nationally Determined Contributions, the CO2 emissions from individual fossil fuel projects can, within decades, dominate and even exceed legislated national emission limits. The practical, future-focused approaches demonstrated here offer a critical bridge between climate science and decision-making, with immediate relevance to choices that will shape Earth’s climate for decades to centuries to come
Understanding the impact of modelling assumptions and population heterogeneity on the robustness of outputs of different epidemiological models in the context of the COVID-19 pandemic and beyond
Get PDFThe rapid emergence of the SARS-CoV-2 virus in late 2019 and its high virulence generated extensive public interest from both specialists and non-specialists alike and has highlighted the importance of mathematical modelling in epidemiology.
In this DPhil project, we explore how differing modelling approaches used in epidemiology can impact the recommendations made by scientists and scientific advisory groups to policy makers in Government, with a particular focus on the decisions made in the UK during the COVID-19 pandemic. The first major focus of this work revolves around a class of models popularly used in epidemiology, known as renewal models. These models require fewer assumptions to be made compared to alternative modelling techniques, yet still output quantities of relevance to policy. Classic renewal modelling approaches treat a population as a homogeneous group and ignore differences in contact patterns that may vary systematically across groups (e.g. that teenagers typically have more contacts per day than those aged 65+). We develop de novo renewal models to incorporate the effects of population heterogeneity for better prediction of public health outcomes, and derive straightforward and entirely new mathematical results to assess the long-term behaviour of a pathogen within a multi-layered population.
Finally, we compare three of the key compartmental models that were used by the UK government and the industrial research sector to model the COVID-19 UK epidemic. We reimplement these models in a unified framework using industrial-strength software engineering practices by creating an open-source package called ‘epimodels’ [Bouros, 2021]. This work highlights the pitfalls of relying on individual models to inform policy responses for future epidemics and pandemics, as well as the need for a more in-depth study of the impact of modelling assumptions on the quality of model outputs
Dynamic models for clean energy technology diffusion and improvement
Get PDFMitigating global warming is one of the most significant structural transformations under- taken by society. The energy sector is central to this endeavour since it currently accounts for over 73% of global greenhouse gas emissions and trillions of USD in fossil fuel assets. Increased adoption of clean energy technologies, such as solar photovoltaics, onshore wind, and battery-electric vehicles plays an central role in the energy transition by displacing incumbent fossil fuel technologies.
In this thesis, I study dynamic models of future clean energy technology diffusion and cost in the face of uncertainty. I answer key questions about the energy transition whilst advancing statistical models of technological change.
In my first paper, I critically examine recent models which have forecasted limits to the diffusion of solar photovoltaics and onshore wind, finding that many results are not robust due to underlying uncertainty and the lack of statistical rigour in the assessments. Global solar and wind deployment have not significantly departed from their exponential growth trajectory so far, and there are no reliable signs when they will do so.
For my second paper, I apply more reliable statistical methods to develop forecasts for national solar and wind costs. Based on their decomposition, solar costs will likely decline further, but wind may soon reach its floor cost. Solar levelised costs of electricity in different countries will most likely converge in the future due to a high degree of correlation between countries. Wind costs, however, will likely continue to display cross-sectional variations of almost an order of magnitude due to differences in natural resources.
My third paper uses similar forecasts to develop dynamic investment strategies in technology portfolios under uncertainty and learning. For instance, in the case of battery- electric passenger vehicles, assuming low discount rates and negligible switching costs, we are now at a tipping point where it is no longer cost-optimal to invest in traditional combustion-based vehicles. However, with an discount rates above 2%, continued policy support is required if the transport sector is to reach this tipping point
Does lifestyle explain the relationship between socioeconomic position and multimorbidity of cancer and cardiometabolic diseases? A mediation analysis applied to the European Prospective Investigation into Cancer and Nutrition
Get PDFBackground: Multimorbidity is socially patterned, with lower socioeconomic position (SEP) linked to higher risk. We examined whether a Healthy Lifestyle Index (HLI) mediates the SEP–multimorbidity association and whether pathways differ by sex. Methods: We used data from 244 886 participants in the European Prospective Investigation into Cancer and Nutrition study. HLI was derived from smoking, alcohol consumption, physical activity, body mass index and diet. SEP was categorised into low, medium and high-SEP based on education. Multimorbidity was defined as the coexistence of at least two diseases among cancer, type 2 diabetes and cardiovascular diseases. Logistic regression assessed SEP-HLI association, Cox regression SEP-multimorbidity and HLI-multimorbidity associations. Counterfactual mediation analysis estimated the natural indirect effect (NIE) and pure direct effect (PDE). Analyses were stratified by sex. Results: Participants from lower SEP categories were older with worse health outcomes. Women had a healthier lifestyle than men across all SEP levels. In men, the hazard ratio of developing multimorbidity was 1.40 (95% CI: 1.26 to 1.54) for those with low SEP compared with high SEP, in women 1.74 (95% CI: 1.52 to 2.00). Comparing low versus high SEP, PDE for men was 1.28 (95% CI: 1.15 to 1.41), NIE was 1.09 (95% CI: 1.07 to 1.11) (proportion mediated (PM)=29%). In women, PDE was 1.65 (95% CI: 1.47 to 1.90), NIE 1.05 (95% CI: 1.03 to 1.06) (PM=11%). Conclusions: Lifestyle behaviours partly mediated the SEP-multimorbidity association, underscoring the need to integrate considerations of socioeconomic disparities into the planning of lifestyle interventions