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Autoencoders reveal polyunsaturated fatty acids (PUFA)-Related metabolic signature linked to cancer risk
Get PDFBackgroundMetabolomics is a valuable tool for characterising biological mechanisms involved in cancer development, but produces complex datasets with intricate interdependencies. While linear dimension reduction techniques such as principal component analysis (PCA), have proven useful to summarise informative hidden patterns, biological evidence suggests metabolic relationships extend beyond linearity. Non-linear dimension reduction techniques, such as autoencoders (AEs), may identify more meaningful components.MethodsWe applied AEs and PCA to metabolomic data available for 5828 matched case-control pairs from 8 cancer-specific case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, and compared their performance. We evaluated the association between components identified by AEs and PCA with cancer risk, and explored the biological interpretation of components through their association with genetic factors and selected biomarkers.FindingsPCA and AEs showed similar reconstruction performance. PCA's first component (PCA.1) captured phosphatidylcholines (PCs) as the primary source of variability and was associated with cancer risk. Conversely, AEs decomposed PC metabolism into two components, one of which exhibited a stronger association with cancer risk than PCA.1. Unlike PCA.1, this component was strongly associated with genetic variants mapping to the TMEM258 and FADS genes, key in polyunsaturated fatty acids (PUFA) biosynthesis and regulation. Consistently, the AE component demonstrated stronger associations with circulating omega-3 and omega-6 PUFA levels than PCA.1.InterpretationLinear methods remain adequate for general dimension reduction. However, AEs better captured specific pathways, identifying a component reflecting perturbations in PUFA metabolism associated with cancer risk.FundingWorld Cancer Research Fund (IIG_FULL_2022_013)
Quantifying roadless areas and fragmentation in the context of wildlife-vehicle collision risk in Great Britain
Get PDFRoads cause indirect and direct effects for wildlife, including pollution, behavioural changes, wildlife mortality and habitat fragmentation. The ecological impacts of roads extend beyond their immediate vicinity, into ‘road effect zones’. Beyond road effect zones, ‘roadless areas’ can offer refuges from the ecological effects of roads. In this study, we quantify the number and distribution of roadless patches in Great Britain, their ecological status and their overlap with protected areas. Road effect zones applied 100, 500 and 1,000 m on either side of the road network revealed a highly fragmented landscape with 93,561, 29,164 and 6,138 roadless patches, covering 76.6%, 36.0% and 20.6% of terrestrial land, respectively. Roadless areas were smallest, on average, in England and largest in Scotland. For all road effect zones, more than 70% of patches were smaller than 1 km2. For the most commonly used road effect zone (1 km), more than 60% of roadless patches were smaller than the mean home range of common UK species, European badger Meles meles and red fox Vulpes vulpes, meaning they likely face a high risk of wildlife-vehicle collisions. Nearly half (47%) of roadless areas coincided with protected land and there was a weak but significant negative relationship between roadless patch size and ecological status. In conclusion, the landscape is fragmented into numerous, small roadless patches. We present roadless areas and their ecological features as an open access searchable map, constituting a tool for conservation practitioners and an important starting point for defragmentation campaigns
Measuring Multidimensional Poverty: A Rigorously Documented Global Data Gap
Get PDFThis paper presents a three-stage in-depth review of multi-topic household surveys to assess whether existing data could be used to estimate a truly global moderate Multidimensional Poverty Index (MPI) that is frequently updated and extensively disaggregated. Drawing on previous studies it first summarises data sources presently used for international or national MPIs, setting out some advantages and drawbacks. The review then sets out criteria used for selection and assessment of reviewed datasets, and schematically presents survey contents and their cross-national comparability. It then assesses potential indicators for comparable multidimensional poverty indices, and identifies data gaps according to reviewed datasets. Additionally, the paper highlights some common shortcomings and comparability issues found in multi-topic household surveys, and proposes feasible adjustments. While this paper covers 152 suitable household surveys and 3 cross-country datasets, it cannot be an exhaustive review. Nor does it claim to assess the suitability of the reviewed surveys for any other purposes. It assesses data availability for a set of concrete structures of internationally comparable, frequently updated, and subnationally disaggregated moderate MPIs, in the hope of closing the gap towards global coverage. It uncovers a large data gap and sets out recommendations to address it
Comparative safety, efficacy, and predictors of complete occlusion of flow diverter devices in the treatment of unruptured distal anterior cerebral artery aneurysms
Get PDFBackground: Flow diverters (FDs) are increasingly used for cerebral aneurysms, including distal anterior cerebral artery (DACA) aneurysms, but comparative data between devices in this challenging location are limited. Objective: To compare the safety and efficacy of Pipeline, Silk Vista Baby (SVB), and FRED Jr. FDs for unruptured DACA aneurysms and identify predictors of complete occlusion. Methods: We retrospectively analyzed 166 patients treated with FDs at 39 centers in 14 countries (2018–2022) from the CRETA registry. Outcomes included aneurysm occlusion (O’Kelly–Marotta [OKM] scale), complications, retreatment, modified Rankin Scale (mRS) scores, and independent predictors of complete occlusion using multivariable Cox regression. Results: Aneurysms were predominantly saccular and located on the pericallosal artery. Complete occlusion (OKM D) was achieved in 73%, and neck remnants (OKM C) in 12%, with no differences across devices. Ischemic complications occurred in 11% (mostly asymptomatic), hemorrhagic complications in 5%, and in-stent stenosis in 17%. Retreatment was performed in 1.3%. At last follow-up, 98% had mRS ≤ 2. Independent predictors of complete occlusion were female sex (HR 1.85), asymptomatic presentation (HR 1.79), smaller aneurysm neck (HR 0.83/mm), radial access (HR 2.20), and aspirin plus ticagrelor therapy (HR 1.84); device type was not predictive. Conclusion: Pipeline, SVB, and FRED Jr. FDs show similar safety and efficacy for unruptured DACA aneurysms. Complete occlusion is influenced by clinical and procedural factors, supporting individualized device selection
Matthew Paris’ manuscripts: working books and artefacts in medieval and early modern collections
No full textThis chapter traces the material lives of the manuscripts written, annotated, and illustrated by Matthew Paris, following them from their creation as working books at St Albans Abbey through successive regimes of use, collecting, and conservation from the later Middle Ages to the present. Unlike most medieval authors, Matthew survives in an unusually large corpus of autograph and semi-autograph manuscripts, which together form not merely witnesses to texts but a coherent archive of authorial practice, revealing modes of historical, hagiographical, and scientific writing that were at once personal and collaborative, structurally fluid, and responsive to audience, patronage, and circumstance. By reconstructing the codicological histories of these books, the chapter shows how they functioned as mutable artefacts within a living monastic library, subject to rearrangement, expansion, lending, and display, before examining the rupture caused by the dissolution of the monasteries, when Matthew’s manuscripts were dispersed into royal and private collections and reinterpreted through early modern antiquarian, confessional, and aesthetic priorities. The interventions of collectors such as Matthew Parker and Robert Cotton—through rebinding, recombination, supplementation, and physical alteration—profoundly reshaped the form in which Matthew Paris has been transmitted and read. The chapter concludes by considering the emergence of modern conservation practices and reproductive technologies, from eighteenth-century restoration after fire to photography, microfilm, and digitization, arguing throughout that Matthew Paris’s reception has been shaped by the survival, handling, and presentation of his manuscripts, which have continually mediated between function and artefact for medieval, early modern, and modern readers
Marking it as her own: early modern women and the Bible
No full textThis essay traces the inky marks left by sixteenth- and seventeen-century women readers in a corpus of 215 vernacular English Bibles and psalm books in the Bodleian Library, Oxford. It asks what information about early modern women as Bible readers can been gleaned from this material evidence and what kind of cultural capital those books accrued by being owned by women. It argues for the importance of female ownership to early modern readers and suggests that the recent interest in female book ownership is, in one sense, a return to early modern mores in which maternal ownership of Bibles made them peculiarly prized
Calibration of local volatility models with stochastic interest rates using optimal transport
No full textWe develop a non-parametric, semimartingale optimal transport, calibration methodology for local volatility models with stochastic interest rate. The method finds a fully calibrated model which is the closest, in a way that can be defined by a general cost function, to a given reference model. We establish a general duality result which allows to solve the problem by optimising over solutions to a second order fully non-linear Hamilton-Jacobi-Bellman equation. Our methodology is analogous to Guo, Loeper, and Wang [29] and Guo et al. [31] but features a novel element of solving for discounted densities, or sub-probability measures. As an example, we apply the method to a sequential calibration problem, where a Vasicek model is already given for the interest rates and we seek to calibrate a stock price’s local volatility model with volatility coefficient depending on time, the underlying and the short rate process, and the two processes driven by possibly correlated Brownian motions. The equity model is calibrated to any number of European options prices
Structural brain differences associated with panic disorder: an ENIGMA-anxiety working group megaanalysis of 4,924 individuals worldwide
No full textNeuroanatomical findings on panic disorder (PD) are typically difficult to replicate, with inconsistent effects. These concerns prompted a paradigm shift towards large-scale collaborations, focused on harmonized data extraction and processing for robust examination of PD brain correlates. Hence, leveraging the largest-ever multi-site neuroimaging database on PD (Age: 10-66 years; global sites: 28), compiled by the ENIGMA-Anxiety Working Group, we report on cortical and subcortical differences in individuals with PD (N=1,146) versus healthy controls (HC: N=3,778). The analyses revealed lower thickness and smaller cortical surface area within fronto-temporo-parietal regions in PD (Cohen’s ds: -0.08 to -0.13), along with lower thalamic and caudate volumes (Cohen’s ds: -0.07 to -0.12). Diagnosis-by-age2 interactions (Cohen’s ds: 0.07 to 0.12) revealed lower thickness in individuals with PD compared to HC in certain regions during adulthood (25-55 years), with relative absence of such differences during youth (55 years). Finally, patient subgroup analyses showed that early disease onset (≤21 years) in PD was associated with larger lateral ventricles (Cohen’s ds: 0.31 to 0.38), whilst no medication, comorbidity, or severity effects were found. These findings lend support to neurocircuitry models of PD, which postulate differences within fronto-striato-limbic circuits and temporo-parietal regions. Moreover, findings highlight the potential importance of abnormal development and aging in neuroanatomical differences related to PD. Given its unprecedented scale, the current study is an important milestone towards identifying the structural brain correlates of PD
An exploration of opera-ballet as a music theatre trend: from the Ballets Russes to the present day
No full textThis thesis seeks to shed light on the emergence and evolution of opera-ballet over the past century, providing a foundation for further exploration of this music theatre trend in an accompanying composition portfolio. During the Ballets Russes era in Paris, there was a revival of French baroque stage works. This appears to have inspired, or at least steered, Diaghilev and Benois to shape their answer to Gesamtkunstwerk to align with Parisian tastes for productions where narrative delivery was shared between song and dance. By using the Ballets Russes’ modernist opera-ballets as the foundation for a discussion on more recent works and productions, the second chapter proposes contemporary opera-ballet as a trend within music theatre. The final chapter comprises a critical commentary on the composition portfolio, representing three distinct branches of my compositional aesthetic. Two of these works explore the fusion of contemporary classical and jazz idioms, whilst another two inhabit a contrasting soundworld that utilises a nature-inspired pitch collection. Finally, the major work in my composition portfolio, is "The Orchestras of Auschwitz", which illustrates my creative engagement with ‘found’ music. Specifically, the work incorporates the restoration of music manuscripts previously overlooked in the Auschwitz-Birkenau State Museum
Scaling limist of critical directed graphs
No full textThe scaling limit of connected components in critical undirected random graphs has been well studied and shown to be universal between different critical models of undirected random graphs. Work by Goldschmidt and Stephenson has established the scaling limit of a the strongly connected components of critical directed Erdös-Rényi random graphs.We investigate whether the same scaling limits arise in different critical models of random directed graphs. We study two models in particular: the directed configuration model and inhomogeneous directed random graphs. Our first main result is a scaling limit for the strongly connected components in a critical directed configuration model. Our proofs rely on two main in- gredients: a depth first exploration of the directed configuration model to construct an out-forest for the model and also the identification of a distinguished subset of edges not in the out-forest, called candidates, which are the only edges not in the out-forest which can be part of a strongly connected component. The number of such candidate edges remains bounded asymptotically and will converge to point identifications on the real trees that arise as the scaling limits of the out-forests. We can then extract a directed multigraph with edge lengths by taking the root of each real tree and the point identifications, then orienting each edge away from the root. From these multigraphs, we can extract the con- tinuum strongly connected components. We also present work in progress on establishing a similar scaling limit for a family of rank-1 inhomogeneous random directed Poissonian graphs. We use similar techniques to the directed configuration model but use a coupling with a queueing process instead to construct an out-forest