Verifying the Safety of a Flight-Critical System

This paper describes our work on demonstrating verification technologies on a flight-critical system of realistic functionality, size, and complexity. Our work targeted a commercial aircraft control system named Transport Class Model (TCM), and involved several stages: formalizing and disambiguating requirements in collaboration with do- main experts; processing models for their use by formal verification tools; applying compositional techniques at the architectural and component level to scale verification. Performed in the context of a major NASA milestone, this study of formal verification in practice is one of the most challenging that our group has performed, and it took several person months to complete it. This paper describes the methodology that we followed and the lessons that we learned.Comment: 17 pages, 5 figure

A new Holocene relative sea-level curve for western Brittany (France): Insights on isostatic dynamics along the Atlantic coasts of north-western Europe

International audienceThis study presents new Relative Sea Level (RSL) data that were obtained in the Finistère region (Western tip of Brittany, France) and the implications those data have for the understanding of the isostatic dynamics across north-western Europe, and more specifically along the Atlantic and Channel coasts. New stratigraphic sequences were obtained and analyzed to derive 24 new Sea-level Index Points, in which 6 are basal. These new data considerably increase the knowledge we have of the RSL evolution along the coasts of Western Brittany since the last 8 kyr B.P. From this new dataset, RSL was estimated to rise continuously over the last 8 kyr with a major inflection at ca. 6 kyr cal. BP. Our results show large vertical discrepancies between the RSL records of Brittany and South-Western UK, with the latter plotting several meters below the new data. From this comparison we suggest that the two regions underwent a very different pattern and/or amplitude of subsidence during the last 8 kyr which has implications for the spatial and temporal pattern of the peripheral bulge of the European ice sheets. We compared our data against predictions from Glacio-Isostatic Adjustment models (GIA models). There are large misfits between RSL observations and the predictions of the global (ICE-5G (VM2a) – Peltier, 2004, GLAC1-b – Tarasov and Peltier, 2002; Tarasov et al., 2012, Briggs et al., 2014) and regional UK models (“BIIS” – Bradley et al., 2009; Bradley et al., 2011; “Kuchar”- Kuchar et al., 2012), which can't be resolved through significant changes to the deglaciation history and size of the British–Irish Ice sheet. Paleo-tidal modelling corrections indicate regional changes in the tidal ranges played a negligible role in the data-model misfits. Hence, we propose that the misfits are due to some combination of: (i) unaccounted mass-loss of far-field ice-sheets (Antarctic ice-Sheet or Laurentide Ice-Sheet), (ii) unresolved differences in the deglaciation history and size of the Fennoscandian Ice sheet or, more likely, (iii) significant lateral variations in the Earth's structure across the English Channel

Optimization of the high-throughput synthesis of multiblock copolymer nanoparticles in aqueous media: Via polymerization-induced self-assembly

Over the past fifteen years or so, polymerization-induced self-assembly (PISA) has become widely recognized as a powerful and versatile platform technology for the synthesis of a wide range of block copolymer nanoparticles of controlled size, shape and surface chemistry. In the present study, we report that PISA formulations are sufficiently robust to enable high-throughput experiments using a commercial synthesis robot (Chemspeed Autoplant A100). More specifically, we use reversible addition-fragmentation chain transfer (RAFT) aqueous emulsion polymerization of either n-butyl methacrylate and/or benzyl methacrylate to prepare various examples of methacrylic multiblock copolymer nanoparticles using a poly(methacrylic acid) stabilizer block. Adequate stirring is essential to generate sufficiently small monomer droplets for such heterogeneous polymerizations to proceed efficiently. Good reproducibility can be achieved under such conditions, with well-defined spherical morphologies being obtained at up to 45% w/w solids. GPC studies indicate high blocking efficiencies but relatively broad molecular weight distributions (Mw/Mn= 1.36-1.85), suggesting well-defined (albeit rather polydisperse) block copolymer chains. These preliminary studies provide a sound basis for high-throughput screening of RAFT-mediated PISA formulations, which is likely to be required for commercialization of this technology. Our results indicate that methacrylic PISA formulations enable the synthesis of diblock and triblock copolymer nanoparticles in high overall yield (94-99%) within 1-3 h at 70 °C. However, tetrablocks suffer from incomplete conversions (87-96% within 5 h) and hence most likely represent the upper limit for this approach

Automatic Structure Detection in Constraints of Tabular Data

Abstract. Methods for the protection of statistical tabular data—as controlled tabular adjustment, cell suppression, or controlled rounding— need to solve several linear programming subproblems. For large multi-dimensional linked and hierarchical tables, such subproblems turn out to be computationally challenging. One of the techniques used to reduce the solution time of mathematical programming problems is to exploit the constraints structure using some specialized algorithm. Two of the most usual structures are block-angular matrices with either linking rows (primal block-angular structure) or linking columns (dual block-angular structure). Although constraints associated to tabular data have intrin-sically a lot of structure, current software for tabular data protection neither detail nor exploit it, and simply provide a single matrix, or at most a set of smallest submatrices. We provide in this work an efficient tool for the automatic detection of primal or dual block-angular struc-ture in constraints matrices. We test it on some of the complex CSPLIB instances, showing that when the number of linking rows or columns is small, the computational savings are significant

Alignment of inhaled chronic obstructive pulmonary disease therapies with published strategies :analysis of the Global Initiative for Chronic Obstructive Lung Disease recommendations in SpiroMics

Rationale: Despite awareness of chronic obstructive pulmonary disease (COPD) treatment recommendations, uptake is poor. The Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) spans 2010-2016, providing an opportunity to assess integration of 2011 Global Initiative for Obstructive Lung Disease (GOLD) treatment strategies over time in a large observational cohort study. Objectives: To evaluate how COPD treatment aligns with 2011 GOLD strategies and determine factors associated with failure to align with recommendations. Methods: Information on inhaled medication use collected via questionnaire annually for 4 years was compiled into therapeutic classes (long-acting antimuscarinic agent, long-acting b-agonist, inhaled corticosteroids [ICS], and combinations thereof). Medications were not modified by SPIROMICS investigators. 2011 GOLD COPD categories A, B, C, and D were assigned. Alignment of inhaler regimen with first-/second-line GOLD recommendations was determined, stratifying into recommendation aligned or nonaligned. Recommendation-nonaligned participants were further stratified into overuse and underuse categories. Results: Of 1,721 participants with COPD, at baseline, 52% of regimens aligned with GOLD recommendations. Among participants with nonaligned regimens, 46% reported underuse, predominately owing to lack of long-acting inhalers in GOLD category D. Of the 54% reporting overuse, 95% were treated with nonindicated ICS-containing regimens. Among 431 participants with 4 years of follow-up data, recommendation alignment did not change over time. When we compared 2011 and 2017 recommendations, we found that 47% did not align with either set of recommendations, whereas 35% were in alignment with both recommendations. Conclusions: Among SPIROMICS participants with COPD, nearly 50% reported inhaler regimens that did not align with GOLD recommendations. Nonalignment was driven largely by overuse of ICS regimens in milder disease and lack of long-acting inhalers in severe disease

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer