Relationship between emergency presentation, systemic inflammatory response, and cancer-specific survival in patients undergoing potentially curative surgery for colon cancer

Background Emergency presentation is recognized to be associated with poorer cancer-specific survival following curative resection for colorectal cancer. The present study examined the hypothesis that an enhanced systemic inflammatory response, prior to surgery, might explain the impact of emergency presentation on survival. Methods In all, 188 patients undergoing potentially curative resection for colorectal cancer were studied. Of these, 55 (29%) presented as emergencies. The systemic inflammatory response was assessed using the Glasgow Prognostic Score (mGPS), which is the combination of an elevated C-reactive protein (>10 mg/L) and hypoalbuminemia (<35 g/L). Results In the emergency group, tumor stage was greater (P < 0.01), more patients received adjuvant therapy (P < 0.01) more patients had an elevated mGPS (P < 0.01), and more patients died of their disease (P < 0.05). The minimum follow-up was 12 months; the median follow-up of the survivors was 48 months. Emergency presentation was associated with poorer 3-year cancer-specific survival in those patients aged 65 to 74 years (P < 0.01), in both males and females (P < 0.05), in the deprived (P < 0.01), in patients with tumor-node-metastasis (TNM) stage II disease (P < 0.01), in those who received no adjuvant therapy (P < 0.01), and in the mGPS 0 and 1 groups (P < 0.05) groups. On multivariate survival analysis of patients undergoing potentially curative surgery for TNM stage II colon cancer, emergency presentation (P < 0.05) and mGPS (P < 0.05) were independently associated with cancer-specific survival. Conclusions These results suggest that emergency presentation and the presence of systemic inflammatory response prior to surgery are linked and account for poorer cancer-specific survival in patients undergoing potentially curative surgery for colon cancer. Both emergency presentation and an elevated mGPS should be taken into account when assessing the likely outcome of these patients

The impact of age, sex and socioeconomic deprivation on outcomes in a colorectal cancer screening programme

<p>Background: Population-based colorectal cancer screening has been shown to reduce cancer specific mortality and is used across the UK. Despite evidence that older age, male sex and deprivation are associated with an increased incidence of colorectal cancer, uptake of bowel cancer screening varies across demographic groups. The aim of this study was to assess the impact of age, sex and deprivation on outcomes throughout the screening process.</p> <p>Methods: A prospectively maintained database, encompassing the first screening round of a faecal occult blood test screening programme in a single geographical area, was analysed.</p> <p>Results: Overall, 395 096 individuals were invited to screening, 204 139 (52%) participated and 6 079 (3%) tested positive. Of the positive tests, 4 625 (76%) attended for colonoscopy and cancer was detected in 396 individuals (9%). Lower uptake of screening was associated with younger age, male sex and deprivation (all p<0.001). Only deprivation was associated with failure to proceed to colonoscopy following a positive test (p<0.001). Despite higher positivity rates in those that were more deprived (p<0.001), the likelihood of detecting cancer in those attending for colonoscopy was lower (8% most deprived vs 10% least deprived, p = 0.003).</p> <p>Conclusion: Individuals who are deprived are less likely to participate in screening, less likely to undergo colonoscopy and less likely to have cancer identified as a result of a positive test. Therefore, this study suggests that strategies aimed at improving participation of deprived individuals in colorectal cancer screening should be directed at all stages of the screening process and not just uptake of the test.</p&gt

Using Flow Specifications of Parameterized Cache Coherence Protocols for Verifying Deadlock Freedom

We consider the problem of verifying deadlock freedom for symmetric cache coherence protocols. In particular, we focus on a specific form of deadlock which is useful for the cache coherence protocol domain and consistent with the internal definition of deadlock in the Murphi model checker: we refer to this deadlock as a system- wide deadlock (s-deadlock). In s-deadlock, the entire system gets blocked and is unable to make any transition. Cache coherence protocols consist of N symmetric cache agents, where N is an unbounded parameter; thus the verification of s-deadlock freedom is naturally a parameterized verification problem. Parametrized verification techniques work by using sound abstractions to reduce the unbounded model to a bounded model. Efficient abstractions which work well for industrial scale protocols typically bound the model by replacing the state of most of the agents by an abstract environment, while keeping just one or two agents as is. However, leveraging such efficient abstractions becomes a challenge for s-deadlock: a violation of s-deadlock is a state in which the transitions of all of the unbounded number of agents cannot occur and so a simple abstraction like the one above will not preserve this violation. In this work we address this challenge by presenting a technique which leverages high-level information about the protocols, in the form of message sequence dia- grams referred to as flows, for constructing invariants that are collectively stronger than s-deadlock. Efficient abstractions can be constructed to verify these invariants. We successfully verify the German and Flash protocols using our technique

SMT-based Model Checking for Recursive Programs

We present an SMT-based symbolic model checking algorithm for safety verification of recursive programs. The algorithm is modular and analyzes procedures individually. Unlike other SMT-based approaches, it maintains both "over-" and "under-approximations" of procedure summaries. Under-approximations are used to analyze procedure calls without inlining. Over-approximations are used to block infeasible counterexamples and detect convergence to a proof. We show that for programs and properties over a decidable theory, the algorithm is guaranteed to find a counterexample, if one exists. However, efficiency depends on an oracle for quantifier elimination (QE). For Boolean Programs, the algorithm is a polynomial decision procedure, matching the worst-case bounds of the best BDD-based algorithms. For Linear Arithmetic (integers and rationals), we give an efficient instantiation of the algorithm by applying QE "lazily". We use existing interpolation techniques to over-approximate QE and introduce "Model Based Projection" to under-approximate QE. Empirical evaluation on SV-COMP benchmarks shows that our algorithm improves significantly on the state-of-the-art.Comment: originally published as part of the proceedings of CAV 2014; fixed typos, better wording at some place

Variable Reuse for Efficient Image Computation

Image computation, that is, computing the set of states reachable from a given set in one step, is a crucial component in typical tools for BDD-based symbolic reachability analysis. It has been shown that the size of the intermediate BDDs during image computation can be dramatically reduced via conjunctive partitioning of the transition relation and ordering the conjuncts for facilitating early quantification. In this paper, we propose to enhance the effectiveness of these techniques by reusing the quantified variables. Given an ordered set of conjuncts, if the last conjunct that uses a variable u appears before the first conjunct that uses another variable v, then v can be renamed to u, assuming u will be quantified immediately after its last use. In general, multiple variables can share the same identifier so the BDD nodes that are inactive but not garbage collected may be activated. We give a polynomial-time algorithm for generating the optimum number of variables that are required for image computation and show how to modify the image computation accounting for variable reuse. The savings for image computation are demonstrated on ISCAS\u2789 and Texas\u2797 benchmark models

Role of dipolar and exchange interactions in the positions and widths of EPR transitions for the single-molecule magnets Fe8 and Mn12

We examine quantitatively the temperature dependence of the linewidths and line shifts in electron paramagnetic resonance experiments on single crystals of the single-molecule magnets Fe$_8$ and Mn$_{12}$, at fixed frequency, with an applied magnetic field along the easy axis. We include inter-molecular spin-spin interactions (dipolar and exchange) and distributions in both the uniaxial anisotropy parameter $D$ and the Land\'{e} $g$-factor. The temperature dependence of the linewidths and the line shifts are mainly caused by the spin-spin interactions. For Fe$_8$ and Mn$_{12}$, the temperature dependence of the calculated line shifts and linewidths agrees well with the trends of the experimental data. The linewidths for Fe$_8$ reveal a stronger temperature dependence than those for Mn$_{12}$, because for Mn$_{12}$ a much wider distribution in $D$ overshadows the temperature dependence of the spin-spin interactions. For Fe$_8$, the line-shift analysis suggests two competing interactions: a weak ferromagnetic exchange coupling between neighboring molecules and a longer-ranged dipolar interaction. This result could have implications for ordering in Fe$_8$ at low temperatures.Comment: published versio

Complementarity in classical dynamical systems

The concept of complementarity, originally defined for non-commuting observables of quantum systems with states of non-vanishing dispersion, is extended to classical dynamical systems with a partitioned phase space. Interpreting partitions in terms of ensembles of epistemic states (symbols) with corresponding classical observables, it is shown that such observables are complementary to each other with respect to particular partitions unless those partitions are generating. This explains why symbolic descriptions based on an \emph{ad hoc} partition of an underlying phase space description should generally be expected to be incompatible. Related approaches with different background and different objectives are discussed.Comment: 18 pages, no figure

Subsumer-First: Steering Symbolic Reachability Analysis

Abstract. Symbolic reachability analysis provides a basis for the veri-fication of software systems by offering algorithmic support for the ex-ploration of the program state space when searching for proofs or coun-terexamples. The choice of exploration strategy employed by the anal-ysis has direct impact on its success, whereas the ability to find short counterexamples quickly and—as a complementary task—to efficiently perform the exhaustive state space traversal are of utmost importance for the majority of verification efforts. Existing exploration strategies can optimize only one of these objectives which leads to a sub-optimal reach-ability analysis, e.g., breadth-first search may sacrifice the exploration ef-ficiency and chaotic iteration can miss minimal counterexamples. In this paper we present subsumer-first, a new approach for steering symbolic reachability analysis that targets both minimal counterexample discovery and efficiency of exhaustive exploration. Our approach leverages the re-sult of fixpoint checks performed during symbolic reachability analysis to bias the exploration strategy towards its objectives, and does not require any additional computation. We demonstrate how the subsumer-first ap-proach can be applied to improve efficiency of software verification tools based on predicate abstraction. Our experimental evaluation indicates the practical usefulness of the approach: we observe significant efficiency improvements (median value 40%) on difficult verification benchmarks from the transportation domain.