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Introduction
No full textThis book began with a conversation during a seminar in Oslo, about the relationship between Latin American poetry and the wider field of Latin American studies. Both editors have studied and written on Latin American poetry and were aware of many other scholars working in the area. Both knew how productive poets and poetry publishers are in the region. And yet, in terms of academic publishing, university courses, and resources more generally, poetry feels like the poor cousin in the Latin American Studies family
The expressiveness and complexity landscape for evaluating formulas over embedded finite models
No full textWe revisit evaluation of logical formulas that allow both uninterpreted relations, constrained to be finite, as well as an interpreted vocabulary over an infinite domain. This formalism was denoted embedded finite model theory in the past. It is clear that the expressiveness and evaluating complexity of formulas of this type depends heavily on the infinite structure. If we embed in a wild structure like the integers with additive and multiplicative arithmetic, logic is extremely expressive and formulas are impossible to evaluate. On the other hand, for some well-known decidable structures, the expressiveness and evaluating complexity are similar to the situation without the additional infrastructure. The latter phenomenon was formalized via the notion of “Restricted Quantifier Collapse”: adding quantification over the infinite structure does not add expressiveness. Beyond these two extremes little was known. In this work we show that the possibilities for expressiveness and complexity are much wider. We show that we can get almost any possible complexity of evaluation while staying within a decidable structure. We also show that in some decidable structures, there is a disconnect between expressiveness of the logic and complexity, in that we cannot eliminate quantification over the structure, but this is not due to an ability to embed complex relational computation in the logic. We show failure of collapse for the theory of finite fields and the related theory of pseudo-finite fields, which will involve coding computation in the logic. As a by-product of this, we establish the first lower bounds for the complexity of decision procedures for several decidable theories of fields, including the theory of finite fields
Influence of stage at cancer diagnosis on NHS hospital care costs in England: a national, retrospective, population-based cohort study using individual patient-level data
No full textBackgroundEstimates of the cost of cancer care are crucial for the economic evaluation of screening interventions and other early cancer diagnosis initiatives. However, data on the cost of cancer is scarce. This study estimated National Health Service (NHS) hospital care costs for eight cancer types by stage at diagnosis in England.MethodsThis national, retrospective, population-based cohort study used individual patient-level data collated by the National Disease Registration Service, NHS England. We included patients aged 50–79 years who were diagnosed with a colorectal, head and neck, liver and bile duct, lung, lymphoma, oesophageal, ovarian, or pancreatic cancer in England between Jan 1, 2014, and Dec 31, 2017. For each patient, we obtained linked national health-care records, incorporating all inpatient hospital care, outpatient activity, and accident and emergency department attendances, and costed these using a payer perspective. Patients were excluded if registration was death certificate only, records related only to a secondary metastatic site, sex and cancer type were incompatible, death status or date were uncertain, or there were zero health-care costs from 6 months before diagnosis to end of follow-up. Net, cancer-related, regression-adjusted hospital care costs were reported for each cancer type and stage overall, annually, and by phase of care. Within each annual period and phase, mean monthly costs were also estimated.FindingsOf 359 106 cancer records registered, 345 629 cancers were available for analysis, and 333 657 cancers were included in the analysis (147 334 [44·2%] occurred in female patients and 186 323 [55·8%] in male patients; 303 227 [90·9%] among participants of White ethnicity, 4452 [1·3%] among participants of mixed or other ethnicity, 7870 [2·3%] among participants of Asian ethnicity, 4179 [1·3%] among participants of Black ethnicity, and 13 929 [4·2%] among participants of unknown ethnicity). Overall costs were higher at later stages for colorectal, head and neck, lymphoma, and ovarian cancers with mean stage IV costs of £37 838, £36 657, £42 667, and £45 871, respectively. Costs for liver and bile duct, lung, oesophageal, and pancreatic cancers were highest for those diagnosed at stage II (£28 356, £29 553, £33 640, and £39 351, respectively), and slightly lower at stages I, III, and IV. Health-care costs were highest in the initial treatment and the end-of-life phases of care. Within each phase, mean cost per month increased with stage for most cancer types studied, though fewer months of follow-up were observed in each phase for liver and bile duct, lung, oesophageal, and pancreatic cancers.InterpretationCancer-related NHS hospital care costs by stage at diagnosis differed between cancer types; this heterogeneous pattern could inform detailed and nuanced economic evaluations of early detection initiatives.FundingGRAIL Bio UK
DNA sequencing of Linnaeus's Ulva compress, U. intestinalis, and U. linza (Ulvaceae, Chlorophyta) and other Ulva type specimens
Get PDFThe names published by Linnaeus in Species Plantarum represent the foundation of modern plant taxonomy. Despite their systematic value, very few of Linnaeus's original type specimens have been analyzed using current DNA sequencing technologies. Here, we performed high-throughput sequencing on Linnean and other type specimens of Ulva, a genus of ecological and commercial importance. Chloroplast and mitochondrial genomes were assembled for Linnaeus's U. compressa, U. intestinalis, U. lanceolata, and U. linza as well as Kützing's Phycoseris smaragdina type specimens. Phylogenetic analyses of these data showed that the names U. compressa and U. intestinalis were correctly applied, but U. linza and U. lanceolata were misapplied. Ulva linza is the earliest available name for the European species currently called U. pseudocurvata. The correct name for the globally distributed species previously known as U. “linza” is Ulva smaragdina (Kützing) comb. nov. The names Ulva lanceolata, U. crispata, and Phycoseris olivacea do not represent distinct species, instead being heterotypic synonyms of U. compressa, and P. planifolia is a heterotypic synonym of U. intestinalis. These results demonstrate that genetic characterization of type material can unequivocally resolve longstanding taxonomic debates over scientific names
A hybrid compass mechanism combining radical pairs and magnetite crystals
Get PDFThat night-migratory songbirds have a magnetic compass sense is undisputed. The nature of the sensor, however, is far from certain. The two leading hypotheses are organic radical pairs in cryptochrome flavoproteins and crystals of inorganic magnetic minerals such as magnetite. Here, we propose a magnetoreception mechanism that combines radical pair chemistry with magnetite nanoparticles. Instead of directly detecting the tiny dependence of a radical pair reaction on the direction of the Earth’s (~50 μT) magnetic field, this hybrid sensor uses a magnetic particle to amplify the Earth’s field. Directional information is thereby encoded in the response of nearby radical pairs to the intensity of a much stronger (~5 mT) magnetic field. The result is a magnetoreceptor with potentially 10 to 100-fold greater sensitivity than afforded by radical pairs alone
T‐Cell‐Derived Exosomes From Multi Core Granules Exhibit Superior Caspase‐3‐Mediated Tumor‐Suppressive Activity Compared to Those From Multivesicular Bodies
Get PDFSmall extracellular vesicles (sEVs) derived from cytotoxic T lymphocytes (CTLs) are emerging as potential mediators of antitumor immunity; however, their subcellular origins and functional properties remain incompletely defined. In this study, we investigated the intracellular routes and cytotoxic potential of CTL‐derived exosomes. Using correlative light and electron microscopy, we discovered that CTL‐derived exosomes originate from both classical multivesicular bodies (MVBs) and the recently identified multi core granules (MCGs). Through total internal reflection fluorescence microscopy, we demonstrated that, in contrast to MVB‐derived exosomes, MCG‐derived exosomes are released at the immunological synapse in a stimulus‐dependent manner. To enable functional characterization, we developed a scalable primary cell culture method for the isolation of high‐purity exosomes. Super‐resolution microscopy revealed significant heterogeneity in exosome size and tetraspanin composition. Notably, MCG‐derived exosomes exhibited fivefold higher cytotoxic activity than MVB‐derived exosomes, inducing apoptosis in tumor cells via a caspase 3‐dependent mechanism. These findings reveal that CTLs exploit distinct secretory pathways to release heterogeneous exosome populations with differential cytotoxic capacities, offering new insights into CTL‐mediated immune responses and providing a basis for the development of novel exosome‐based immunotherapies
Installing and understanding group-13 x-type metallo-ligands
Get PDFThis thesis describes synthetic, spectroscopic and computational efforts to access and understand metal complexes of the trielyl ligands, i.e. X-type ligands for the form EX2 - , where E is a group 13 element in the +1 oxidation state. In particular, this thesis focusses on understanding aluminyl ligands (E = Al). Such compounds receive much attention in the current literature, as the electropositive nature of aluminium renders aluminyl ligands highly electron donating. Such properties are best understood through comparison with lighter and heavier congeners (and also other related ligands from across the Periodic Table), and so this thesis additionally explores boryl complexes, and series of isostructural compounds bearing aluminyl, gallyl and indyl metallo-ligands (E = Al, Ga and In respectively).Chapter 1 introduces the group 13 elements, and discusses their use as ligands to metal centres. Ligand modes which involve low valent metal centres (L- and X- type ligation) receive the most attention, with a particular focus on the X-type ligands (trielyls). Aluminyl ligands are tackled last, with a discussion of all metal-aluminyl complexes reported to date.Chapters 2-6 take the form of papers. Chapters 4 and 6 are published papers, chapter 2 is a submitted manuscript, and chapters 3 and 5 are draft manuscripts presented in publication format. In all cases, I am the first author, having conducted a significant majority (or in some cases all) of the synthesis, crystallographic and spectroscopic characterisation, sample preparation, computational analysis, and preparation of the manuscript text and supplementary information. A declaration to this effect can be found at the end of each chapter, signed by myself and my supervisor Prof. Simon Aldridge.Chapter 2 details the synthesis of a zinc boryl complex, with the goal of comparing its reactivity to that of its reported aluminyl congener. Both the synthesis and onward chemistry of this species are dominated by B–O bond formation, which is further exploited to access a zinc(I) compound bearing a Zn–Zn bond without the need for alkali metal reductions.Chapter 3 makes use of the aforementioned zinc boryl and aluminyl complexes, as well as a family of related Zn–X compounds. These are studied by X-ray spectroscopy in order to probe and compare the ligand properties of these X ligands, via the electronic structure they induce at the zinc centre. These data are rationalised in terms of common models of chemical bonding, and also compared to parameters generated by computational analysis of the compounds studied. In this way, computational techniques are evaluated against experimental data, identifying which techniques most effectively capture the measured trends for potential extrapolation of this analysis to other Xtype ligands.Chapter 4 describes the convenient synthesis of sources of the indium trielyl congener (indyl anion) via indium(I) precursors, and applies them in the synthesis of isostructural series of linear d10 metal complexes bearing aluminyl, gallyl and indyl ligands. Spectroscopic and structural probes inherent within these molecules are then used to evaluate the trans influence of these trielyl ligands.Chapter 5 investigates the reactivity of aluminyl, gallyl and indyl anions with Fe(CO)5 in order to access iron-trielyl complexes of the form [Fe(CO)4EX2] - (E = Al, Ga, In). In the aluminium case, undesired products due to redox processes and Al–O bond formation are observed, with tuning of the counterion required to access the target motif. More facile access to Fe–E bonded products is observed for the heavier congeners, and a range of techniques (IR, Mössbauer, crystallography, computational analysis) are used to compare the behaviour of the trielyl ligands in the resulting complexes. Chapter 6 discusses the synthesis and reactivity of a bis(aluminyl) magnesium compound. Whilst the relatively covalent Al–Mg bonds serve to curtail the reactivity of the aluminyl anion, this species is nonetheless able to activate small molecule substrates such as the kinetically inert gas SF6. Despite a thermal reactivity profile consistent with the more expected Al(I)–Mg(II)–Al(I) description of this trimetallic compound, photolytic reactivity (which both eliminates magnesium metal and yields products associated with radical intermediates) indicates that this species can also act as a Al(II)–Mg(0)–Al(II) synthon. Such unusual reactivity highlights the effect that a strongly electron donating aluminyl ligand can have on the reactivity of a metal complex. Finally, chapter 7 draws on the results of the previous chapters to offer overall conclusions from this work, and suggest areas where future study might be particularly fruitful. The research presented in this thesis has generated a range of data quantifying the donor properties of the aluminyl metalloligand, as compared to its group 13 congeners and other X-type ligands from across the Periodic Table. These data have demonstrated its extremely σ-donating nature, and the unusual effects this can have on the electronic structure of a metal centre. The possibility of accessing isostructural series presented by this thesis has allowed for the chemistry of group 13 ligands based on the metals aluminium, gallium and indium to be evaluated without complications arising from differing supporting ligands, showing a decrease in donor-strength as the group is descended. Additionally, this thesis has helped to establish design principles for the synthesis of metal aluminyl complexes. These include both coligand choice to ensure the stability of the complex, and methodological considerations for preventing unwanted reactivity when installing aluminyl ligands
History-writing as a scientific intervention: chemistry and its histories, 1750–1800
Get PDFThe thesis analyses histories of chemistry as interventions in scientific praxis in France and Germany between 1750 and 1800. It explores how, through the form and content of works on the history of their field, chemists positioned themselves in methodological and epistemological controversies which arose both from chemical investigations and from the chemists’ interactions with neighbouring fields. Additionally, historical narratives responded to controversies on the discipline’s methodology voiced by other naturalists and served to consolidate its contested status within academic institutions. The chemist-historians flexibly adopted methods and concepts from other contemporary realms of historical inquiry. Thus, they created a diverse body of literarily complex and conceptually advanced historical works.
After an overview of chemistry as a field of study and its place in the Republic of Letters in chapter 1, the thesis shows how mid eighteenth-century histories of chemistry were designed to suggest that chemical methods conformed with the standards postulated by prominent philosophies of the natural sciences. By applying the techniques of conjectural history-writing, the evolution of chemistry’s investigative practices was portrayed as a standard case of scientific progress in the natural sciences. Additionally, critical historical investigations featured in a debate on the status of alchemy and the uneasy heritage of hermetic philosophy. The second part of the thesis concentrates on the Chemical Revolution (chapter 2). In the 1780s, Antoine de Lavoisier surveyed the detrimental effect which theoretical preconceptions and nomenclature had had on chemistry’s progress to defend his approach against British critics. Numerous German chemists critically revised Lavoisier’s claims and drafted innovative histories of the field to mark their position in the debate (chapter 3 and 4). Concomitantly, the French chemist Antoine de Fourcroy defended Lavoisier’s claims by historicising various aspects of the latter’s theory and by reconstructing its emergence in the interdisciplinary setting of Parisian salon culture (chapter 5). Thus, by 1800, a wide array of methods and concepts had emerged to address the evolution of knowledge, in chemistry and beyond
How Well Do Governments Assess the Distributional Impacts of Policy?
Get PDFPolicy makers are showing increased interest in understanding the impacts of public policies on subgroups of the population. We provide the first cross‐regional comparison of distributional analyses by examining 907 benefit–cost analyses (BCAs) in the United States, the United Kingdom, and the European Union from 2016 through 2020. In these regions, we find almost no quantification of net benefits for a population subgroup (2 US BCAs, 0 UK BCAs, and 1 EU BCA). Distributional weights were also rarely used (5 UK BCAs, none elsewhere). Moreover, when distributional weights were used in the United Kingdom, they were used mainly to evaluate policies involving income transfers between low‐ and high‐income groups rather than in broader regulatory analyses. We consider possible explanations for the lack of quantification of net benefits by subgroup along with the implications of our findings for conducting distributional analysis. JEL Classification: K23, K32, Q58, I
Brain texture alterations predict subtle visual perceptual dysfunctions in recent onset psychosis and clinical high-risk state
Get PDFDeeper understanding of Subtle Visual Dysfunctions (VisDys) in the early stage of mental illness and their neurobiological underpinnings, as reflected by microstructural brain texture features, could advance our understanding of the underlying disease perceptual mechanisms that mediate susceptibility to psychosis. In this study, we aim a) to investigate the utility of brain texture features for the prediction of VisDys in recent onset psychosis (ROP) and clinical high-risk syndromes for psychosis (CHR-P), respectively, b) to test prediction models established in ROP and CHR-P in an independent validation sample with recent onset depression (ROD) diagnoses and c) to test for symptom expression related brain features associated with VisDys. sMRI were acquired in a training sample including 128 ROP (67 patients with VisDys), 134 CHR-P (71 patients with VisDys). Independent validation sets included 46 ROP (19 with VisDys), 124 CHR-P (68 patients with VisDys) and a sample of 256 ROD (50 patients with VisDys). Both classification schemas in ROP and CHR-P presented balanced accuracy >77% and >64% in the independent validation samples of ROP, CHR-P, and ROD, respectively. Statistically significant associations were identified with scores from the Positive and Negative Symptom Scale, psychosocial functioning, and the Scale of Negative Symptoms