Context-aware Trace Contracts

The behavior of concurrent, asynchronous procedures depends in general on the call context, because of the global protocol that governs scheduling. This context cannot be specified with the state-based Hoare-style contracts common in deductive verification. Recent work generalized state-based to trace contracts, which permit to specify the internal behavior of a procedure, such as calls or state changes, but not its call context. In this article we propose a program logic of context-aware trace contracts for specifying global behavior of asynchronous programs. We also provide a sound proof system that addresses two challenges: To observe the program state not merely at the end points of a procedure, we introduce the novel concept of an observation quantifier. And to combat combinatorial explosion of possible call sequences of procedures, we transfer Liskov's principle of behavioral subtyping to the analysis of asynchronous procedures

Delta-based Verification of Software Product Families

The quest for feature- and family-oriented deductive verification of software product lines resulted in several proposals. In this paper we look at delta-oriented modeling of product lines and combine two new ideas: first, we extend Hähnle & Schaefer’s delta-oriented version of Liskov’s substitution principle for behavioral subtyping to work also for overridden behavior in benign cases. For this to succeed, programs need to be in a certain normal form. The required normal form turns out to be achievable in many cases by a set of program transformations, whose correctness is ensured by the recent technique of abstract execution. This is a generalization of symbolic execution that permits reasoning about abstract code elements. It is needed, because code deltas contain partially unknown code contexts in terms of “original” calls. Second, we devise a modular verification procedure for deltas based on abstract execution, representing deltas as abstract programs calling into unknown contexts. The result is a “delta-based” verification approach, where each modification of a method in a code delta is verified in isolation, but which overcomes the strict limitations of behavioral subtyping and works for many practical programs. The latter claim is substantiated with case studies and benchmarks

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Delta-based verification of software product families

The quest for feature- and family-oriented deductive verification of software product lines resulted in several proposals. In this paper we look at delta-oriented modeling of product lines and combine two new ideas: first, we extend Hähnle & Schaefer’s delta-oriented version of Liskov’s substitution principle for behavioral subtyping to work also for overridden behavior in benign cases. For this to succeed, programs need to be in a certain normal form. The required normal form turns out to be achievable in many cases by a set of program transformations, whose correctness is ensured by the recent technique of abstract execution. This is a generalization of symbolic execution that permits reasoning about abstract code elements. It is needed, because code deltas contain partially unknown code contexts in terms of “original” calls. Second, we devise a modular verification procedure for deltas based on abstract execution, representing deltas as abstract programs calling into unknown contexts. The result is a “delta-based” verification approach, where each modification of a method in a code delta is verified in isolation, but which overcomes the strict limitations of behavioral subtyping and works for many practical programs. The latter claim is substantiated with case studies and benchmarks

Nutritional Interventions to Improve Clinical Outcomes in Ovarian Cancer: A Systematic Review of Randomized Controlled Trials

Among all gynaecological neoplasms, ovarian cancer has the highest rate of disease-related malnutrition, representing an important risk factor of postoperative mortality and morbidity. Hence, the importance of finding effective nutritional interventions is crucial to improve ovarian cancer patient’s well-being and survival. This systematic review of randomized controlled trials (RCTs) aims at assessing the effects of nutritional interventions on clinical outcomes such as overall survival, progression-free survival, length of hospital stay (LOS), complications following surgery and/or chemotherapy in ovarian cancer patients. Three electronic bibliographic databases (MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials) were used to conduct a systematic literature search based on fixed inclusion and exclusion criteria, until December 2018. A total of 14 studies were identified. Several early postoperative feeding interventions studies (n = 8) were retrieved mainly demonstrating a reduction in LOS and an ameliorated intestinal recovery after surgery. Moreover, innovative nutritional approaches such as chewing gum intervention (n = 1), coffee consumption (n = 1), ketogenic diet intervention (n = 2) or fruit and vegetable juice concentrate supplementation diet (n = 1) and short-term fasting (n = 1) have been shown as valid and well-tolerated nutritional strategies improving clinical outcomes. However, despite an acceptable number of prospective trials, there is still a lack of homogeneous and robust endpoints. In particular, there is an urgent need of RCTs evaluating overall survival and progression-free survival during ovarian oncology treatments. Further high-quality studies are warranted, especially prospective studies and large RCTs, with more homogeneous types of intervention and clinical outcomes, including a more specific sampling of ovarian cancer women, to identify appropriate and effective nutritional strategies for this cancer, which is at high risk of malnutrition