Minimal Synthesis of String To String Functions From Examples

We study the problem of synthesizing string to string transformations from a set of input/output examples. The transformations we consider are expressed using deterministic finite automata (DFA) that read pairs of letters, one letter from the input and one from the output. The DFA corresponding to these transformations have additional constraints, ensuring that each input string is mapped to exactly one output string. We suggest that, given a set of input/output examples, the smallest DFA consistent with the examples is a good candidate for the transformation the user was expecting. We therefore study the problem of, given a set of examples, finding a minimal DFA consistent with the examples and satisfying the functionality and totality constraints mentioned above. We prove that, in general, this problem (the corresponding decision problem) is NP-complete. This is unlike the standard DFA minimization problem which can be solved in polynomial time. We provide several NP-hardness proofs that show the hardness of multiple (independent) variants of the problem. Finally, we propose an algorithm for finding the minimal DFA consistent with input/output examples, that uses a reduction to SMT solvers. We implemented the algorithm, and used it to evaluate the likelihood that the minimal DFA indeed corresponds to the DFA expected by the user.Comment: SYNT 201

Mutation of Directed Graphs -- Corresponding Regular Expressions and Complexity of Their Generation

Directed graphs (DG), interpreted as state transition diagrams, are traditionally used to represent finite-state automata (FSA). In the context of formal languages, both FSA and regular expressions (RE) are equivalent in that they accept and generate, respectively, type-3 (regular) languages. Based on our previous work, this paper analyzes effects of graph manipulations on corresponding RE. In this present, starting stage we assume that the DG under consideration contains no cycles. Graph manipulation is performed by deleting or inserting of nodes or arcs. Combined and/or multiple application of these basic operators enable a great variety of transformations of DG (and corresponding RE) that can be seen as mutants of the original DG (and corresponding RE). DG are popular for modeling complex systems; however they easily become intractable if the system under consideration is complex and/or large. In such situations, we propose to switch to corresponding RE in order to benefit from their compact format for modeling and algebraic operations for analysis. The results of the study are of great potential interest to mutation testing

Emergence of responsible sanctions without second order free riders, antisocial punishment or spite

While empirical evidence highlights the importance of punishment for cooperation in collective action, it remains disputed how responsible sanctions targeted predominantly at uncooperative subjects can evolve. Punishment is costly; in order to spread it typically requires local interactions, voluntary participation, or rewards. Moreover, theory and experiments indicate that some subjects abuse sanctioning opportunities by engaging in antisocial punishment (which harms cooperators), spiteful acts (harming everyone) or revenge (as a response to being punished). These arguments have led to the conclusion that punishment is maladaptive. Here, we use evolutionary game theory to show that this conclusion is premature: If interactions are non-anonymous, cooperation and punishment evolve even if initially rare, and sanctions are directed towards non-cooperators only. Thus, our willingness to punish free riders is ultimately a selfish decision rather than an altruistic act; punishment serves as a warning, showing that one is not willing to accept unfair treatments

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD

OBJECTIVE: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. METHODS: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. RESULTS: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. CONCLUSION: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

A three-group study, internet-based, face-to-face based and standard- management after acute whiplash associated disorders (WAD) – choosing the most efficient and cost-effective treatment: study protocol of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The management of Whiplash Associated Disorders is one of the most complicated challenges with high expenses for the health care system and society. There are still no general guidelines or scientific documentation to unequivocally support any single treatment for acute care following whiplash injury.</p> <p>The main purpose of this study is to try a new behavioural medicine intervention strategy at acute phase aimed to reduce the number of patients who have persistent problems after the whiplash injury. The goal is also to identify which of three different interventions that is most cost-effective for patients with Whiplash Associated Disorders. In this study we are controlling for two factors. First, the effect of behavioural medicine approach is compared with standard care. Second, the manner in which the behavioural medicine treatment is administered, Internet or face-to-face, is evaluated in it's effectiveness and cost-effectiveness.</p> <p>Methods/Design</p> <p>The study is a randomized, prospective, experimental three-group study with analyses of cost-effectiveness up to two-years follow-up. <it>Internet – based programme </it>and <it>face-to-face group treatment programme </it>are compared to <it>standard-treatment </it>only. Patient follow-ups take place three, six, twelve and 24 months, that is, short-term as well as long-term effects are evaluated. Patients will be enrolled via the emergency ward during the first week after the accident.</p> <p>Discussion</p> <p>This new self-help management will concentrate to those psychosocial factors that are shown to be predictive in long-term problems in Whiplash Associated Disorders, i.e. the importance of self-efficacy, fear of movement, and the significance of catastrophizing as a coping strategy for restoring and sustaining activities of daily life. Within the framework of this project, we will develop, broaden and evaluate current physical therapy treatment methods for acute Whiplash Associated Disorders. The project will contribute to the creation of a cost-effective behavioural medicine approach to management of acute Whiplash Associated Disorders. The results of this study will answer an important question; on what extent and how should these patients be treated at acute stage and how much does the best management cost.</p> <p>Trial registration number</p> <p>Current Controlled Trials ISRCTN61531337</p

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD.

Objective: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions: Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

Treatment of neuromyelitis optica: state-of-the-art and emerging therapies.

Neuromyelitis optica (NMO) is an autoimmune disease of the CNS that is characterized by inflammatory demyelinating lesions in the spinal cord and optic nerve, potentially leading to paralysis and blindness. NMO can usually be distinguished from multiple sclerosis (MS) on the basis of seropositivity for IgG antibodies against the astrocytic water channel aquaporin-4 (AQP4). Differentiation from MS is crucial, because some MS treatments can exacerbate NMO. NMO pathogenesis involves AQP4-IgG antibody binding to astrocytic AQP4, which causes complement-dependent cytotoxicity and secondary inflammation with granulocyte and macrophage infiltration, blood-brain barrier disruption and oligodendrocyte injury. Current NMO treatments include general immunosuppressive agents, B-cell depletion, and plasma exchange. Therapeutic strategies targeting complement proteins, the IL-6 receptor, neutrophils, eosinophils and CD19--all initially developed for other indications--are under clinical evaluation for repurposing for NMO. Therapies in the preclinical phase include AQP4-blocking antibodies and AQP4-IgG enzymatic inactivation. Additional, albeit currently theoretical, treatment options include reduction of AQP4 expression, disruption of AQP4 orthogonal arrays, enhancement of complement inhibitor expression, restoration of the blood-brain barrier, and induction of immune tolerance. Despite the many therapeutic options in NMO, no controlled clinical trials in patients with this condition have been conducted to date

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics