Parametricity and Local Variables

We propose that the phenomenon of local state may be understood in terms of Strachey\u27s concept of parametric (i.e., uniform) polymorphism. The intuitive basis for our proposal is the following analogy: a non-local procedure is independent of locally-declared variables in the same way that a parametrically polymorphic function is independent of types to which it is instantiated. A connection between parametricity and representational abstraction was first suggested by J. C. Reynolds. Reynolds used logical relations to formalize this connection in languages with type variables and user-defined types. We use relational parametricity to construct a model for an Algol-like language in which interactions between local and non-local entities satisfy certain relational criteria. Reasoning about local variables essentially involves proving properties of polymorphic functions. The new model supports straightforward validations of all the test equivalences that have been proposed in the literature for local-variable semantics, and encompasses standard methods of reasoning about data representations. It is not known whether our techniques yield fully abstract semantics. A model based on partial equivalence relations on the natural numbers is also briefly examined

Syntactic Control of Interference Revisited

In Syntactic Control of Interference (POPL, 1978), J. C. Reynolds proposes three design principles intended to constrain the scope of imperative state effects in Algol-like languages. The resulting linguistic framework seems to be a very satisfactory way of combining functional and imperative concepts, having the desirable attributes of both purely functional languages (such as pcf) and simple imperative languages (such as the language of while programs). However, Reynolds points out that the obvious syntax for interference control has the unfortunate property that fi-reductions do not always preserve typings. Reynolds has subsequently presented a solution to this problem (ICALP, 1989), but it is fairly complicated and requires intersection types in the type system. Here, we present a much simpler solution which does not require intersection types. We first describe a new type system inspired in part by linear logic and verify that reductions preserve typings. We then define a class of bireflective models, which provide a categorical analysis of structure underlying the new typing rules; a companion paper Bireflectivity, in this volume, exposes wider ramifications of this structure. Finally, we describe a concrete model for an illustrative programming language based on the new type system; this improves on earlier such efforts in that states are not assumed to be structured using locations

Plasmin activity promotes amyloid deposition in a transgenic model of human transthyretin amyloidosis

Cardiac ATTR amyloidosis, a serious but much under-diagnosed form of cardiomyopathy, is caused by deposition of amyloid fibrils derived from the plasma protein transthyretin (TTR), but its pathogenesis is poorly understood and informative in vivo models have proved elusive. Here we report the generation of a mouse model of cardiac ATTR amyloidosis with transgenic expression of human TTRS52P. The model is characterised by substantial ATTR amyloid deposits in the heart and tongue. The amyloid fibrils contain both full-length human TTR protomers and the residue 49-127 cleavage fragment which are present in ATTR amyloidosis patients. Urokinase-type plasminogen activator (uPA) and plasmin are abundant within the cardiac and lingual amyloid deposits, which contain marked serine protease activity; knockout of α2-antiplasmin, the physiological inhibitor of plasmin, enhances amyloid formation. Together, these findings indicate that cardiac ATTR amyloid deposition involves local uPA-mediated generation of plasmin and cleavage of TTR, consistent with the previously described mechano-enzymatic hypothesis for cardiac ATTR amyloid formation. This experimental model of ATTR cardiomyopathy has potential to allow further investigations of the factors that influence human ATTR amyloid deposition and the development of new treatments

Constraints on the Ultra High Energy Photon flux using inclined showers from the Haverah Park array

We describe a method to analyse inclined air showers produced by ultra high energy cosmic rays using an analytical description of the muon densities. We report the results obtained using data from inclined events (60^{\circ}<\theta<80^{\circ}) recorded by the Haverah Park shower detector for energies above 10^19 eV. Using mass independent knowledge of the UHECR spectrum obtained from vertical air shower measurements and comparing the expected horizontal shower rate to the reported measurements we show that above 10^19 eV less than 48 % of the primary cosmic rays can be photons at the 95 % confidence level and above 4 X 10^19 eV less than 50 % of the cosmic rays can be photonic at the same confidence level. These limits place important constraints on some models of the origin of ultra high-energy cosmic rays.Comment: 45 pages, 25 figure

Neutrino Detection with Inclined Air Showers

The possibilities of detecting high energy neutrinos through inclined showers produced in the atmosphere are addressed with an emphasis on the detection of air showers by arrays of particle detectors. Rates of inclined showers produced by both down-going neutrino interactions and by up-coming $\tau$ decays from earth-skimming neutrinos as a function of shower energy are calculated with analytical methods using two sample neutrino fluxes with different spectral indices. The relative contributions from different flavors and charged, neutral current and resonant interactions are compared for down-going neutrinos interacting in the atmosphere. No detailed description of detectors is attempted but rough energy thresholds are implemented to establish the ranges of energies which are more suitable for neutrino detection through inclined showers. Down-going and up-coming rates are compared.Comment: Submitted to New Journal of Physic

Formal verification of a memory model for C-like imperative languages

http://www.springer.com/International audienceThis paper presents a formal verification with the Coq proof assistant of a memory model for C-like imperative languages. This model defines the memory layout and the operations that manage the memory. The model has been specified at two levels of abstraction and implemented as part of an ongoing certification in Coq of a moderately-optimising C compiler. Many properties of the memory have been verified in the specification. They facilitate the definition of precise formal semantics of C pointers. A certified OCaml code implementing the memory model has been automatically extracted from the specifications

‘Filip’ or flop? Managing public relations and the Latin American reaction to the 1966 FIFA World Cup

The 1966 FIFA World Cup has become part of the iconography of its hosts and champions, England. Extant literature has tended to focus on the cultural and symbolic legacy of the tournament, or engaged with diplomatic relations between Britain and North Korea. Contrastingly, we use archival sources from footballing and government institutions to explore the less studied topic of how the tournament was reported and perceived in Latin America, where England had commercial interests and influence, but where there were allegations that FIFA, the FA and even the UK government manipulated the tournament to the advantage of England and other European teams. We provide fresh perspectives on the social and cultural significance of the 1966 FIFA World Cup by analysing how the tournament’s organizers attempted to manage the situation and resulting negative public relations, and how 1966 fits within longer-term footballing and diplomatic relations between England and Latin America

Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn's disease (METRIC): a multicentre trial

Magnetic resonance enterography (MRE) and ultrasound are used to image Crohn's disease, but their comparative accuracy for assessing disease extent and activity is not known with certainty. Therefore, we did a multicentre trial to address this issue. We recruited patients from eight UK hospitals. Eligible patients were 16 years or older, with newly diagnosed Crohn's disease or with established disease and suspected relapse. Consecutive patients had MRE and ultrasound in addition to standard investigations. Discrepancy between MRE and ultrasound for the presence of small bowel disease triggered an additional investigation, if not already available. The primary outcome was difference in per-patient sensitivity for small bowel disease extent (correct identification and segmental localisation) against a construct reference standard (panel diagnosis). This trial is registered with the International Standard Randomised Controlled Trial, number ISRCTN03982913, and has been completed. 284 patients completed the trial (133 in the newly diagnosed group, 151 in the relapse group). Based on the reference standard, 233 (82%) patients had small bowel Crohn's disease. The sensitivity of MRE for small bowel disease extent (80% [95% CI 72-86]) and presence (97% [91-99]) were significantly greater than that of ultrasound (70% [62-78] for disease extent, 92% [84-96] for disease presence); a 10% (95% CI 1-18; p=0·027) difference for extent, and 5% (1-9; p=0·025) difference for presence. The specificity of MRE for small bowel disease extent (95% [85-98]) was significantly greater than that of ultrasound (81% [64-91]); a difference of 14% (1-27; p=0·039). The specificity for small bowel disease presence was 96% (95% CI 86-99) with MRE and 84% (65-94) with ultrasound (difference 12% [0-25]; p=0·054). There were no serious adverse events. Both MRE and ultrasound have high sensitivity for detecting small bowel disease presence and both are valid first-line investigations, and viable alternatives to ileocolonoscopy. However, in a national health service setting, MRE is generally the preferred radiological investigation when available because its sensitivity and specificity exceed ultrasound significantly. National Institute of Health and Research Health Technology Assessment. [Abstract copyright: Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Diagnostic accuracy for the extent and activity of newly diagnosed and relapsed Crohn’s disease: a multicentre prospective comparison of magnetic resonance enterography and small bowel ultrasound –The METRIC Trial

Background Magnetic resonance enterography (MRE) and ultrasound (US) are used to image Crohn’s disease, but comparative accuracy for disease extent and activity is not known with certainty. We undertook a prospective multicentre cohort trial to address this Methods We recruited from 8 UK hospitals. Eligible patients were 16 years or older, newly diagnosed with Crohn’s disease, or had established disease with suspected relapse. Consecutive patients underwent MRE and US in addition to standard investigations. Discrepancy between MRE and US for small bowel (SB) disease presence triggered an additional investigation, if not already available. The primary outcome was difference in per patient sensitivity for SB disease extent (correct identification and segmental localisation) against a construct reference standard (panel diagnosis). Accuracy for SB and colonic disease presence and activity were secondary outcomes. The trial is completed (ISRCTN03982913). Findings 284 patients completed the trial (133 new diagnosis, 151 relapse). MRE sensitivity (n=233) for SB disease extent (80% [95%CI 72 to 86]) and presence (97% [91 to 99]) were significantly greater than US (70% [62 to 78], 92% [84 to 96]); a 10% (1 to 18; p=0.027), and 5% (1 to 9), difference respectively. MRE specificity for SB disease extent (95% [85 to 98]) was significantly greater than US (81% [64 to 91]). Sensitivity for active SB disease was significantly greater for MRE than US (96% [92 to 99] vs. 90% [82 to 95]), difference 6% (2 to 11). Overall, there were no significant accuracy differences for colonic disease presence. Accuracy in newly diagnosed and relapse patients was similar, although US had significantly greater sensitivity for colonic disease than MRE in newly diagnosed patients (67% [49 to 81) vs. 47% [31 to 64]), difference 20% (1 to 39). There were no serious adverse events. Interpretation MRE has higher diagnostic accuracy for the extent and activity of SB Crohn’s disease than US when tested in a prospective multi centre cohort trial setting