Automata-theoretic and bounded model checking for linear temporal logic

In this work we study methods for model checking the temporal logic LTL. The focus is on the automata-theoretic approach to model checking and bounded model checking. We begin by examining automata-theoretic methods to model check LTL safety properties. The model checking problem can be reduced to checking whether the language of a finite state automaton on finite words is empty. We describe an efficient algorithm for generating small finite state automata for so called non-pathological safety properties. The presented implementation is the first tool able to decide whether a formula is non-pathological. The experimental results show that treating safety properties can benefit model checking at very little cost. In addition, we find supporting evidence for the view that minimising the automaton representing the property does not always lead to a small product state space. A deterministic property automaton can result in a smaller product state space even though it might have a larger number states. Next we investigate modular analysis. Modular analysis is a state space reduction method for modular Petri nets. The method can be used to construct a reduced state space called the synchronisation graph. We devise an on-the-fly automata-theoretic method for model checking the behaviour of a modular Petri net from the synchronisation graph. The solution is based on reducing the model checking problem to an instance of verification with testers. We analyse the tester verification problem and present an efficient on-the-fly algorithm, the first complete solution to tester verification problem, based on generalised nested depth-first search. We have also studied propositional encodings for bounded model checking LTL. A new simple linear sized encoding is developed and experimentally evaluated. The implementation in the NuSMV2 model checker is competitive with previously presented encodings. We show how to generalise the LTL encoding to a more succint logic: LTL with past operators. The generalised encoding compares favourably with previous encodings for LTL with past operators. Links between bounded model checking and the automata-theoretic approach are also explored.reviewe

Linear Encodings of Bounded LTL Model Checking

We consider the problem of bounded model checking (BMC) for linear temporal logic (LTL). We present several efficient encodings that have size linear in the bound. Furthermore, we show how the encodings can be extended to LTL with past operators (PLTL). The generalised encoding is still of linear size, but cannot detect minimal length counterexamples. By using the virtual unrolling technique minimal length counterexamples can be captured, however, the size of the encoding is quadratic in the specification. We also extend virtual unrolling to Buchi automata, enabling them to accept minimal length counterexamples. Our BMC encodings can be made incremental in order to benefit from incremental SAT technology. With fairly small modifications the incremental encoding can be further enhanced with a termination check, allowing us to prove properties with BMC. Experiments clearly show that our new encodings improve performance of BMC considerably, particularly in the case of the incremental encoding, and that they are very competitive for finding bugs. An analysis of the liveness-to-safety transformation reveals many similarities to the BMC encodings in this paper. Using the liveness-to-safety translation with BDD-based invariant checking results in an efficient method to find shortest counterexamples that complements the BMC-based approach.Comment: Final version for Logical Methods in Computer Science CAV 2005 special issu

Systemic hormonal contraception and risk of venous thromboembolism

Introduction The increased risk of venous thromboembolism associated with the use of hormonal contraception is well recognized, but evidence regarding hormonal contraception containing natural estradiol is limited. This study aimed to assess the associations between the patterns of use of different systemic hormonal contraceptives and the risk of venous thromboembolism during 2017-2019. Material and Methods All fertile-aged women (15-49 years) living in Finland in 2017 and using hormonal contraception in 2017 and their 1:1 age- and residence-matched controls not using hormonal contraception in 2017 (altogether 587 559 women) were selected from the Prescription Centre. All incident venous thromboembolism cases during 2018-2019 and their 4:1 age-matched controls were further analyzed in a prospective nested case-control design to assess the associations between the use (starting, stopping, continuous vs no use) of different hormonal contraception types and venous thromboembolism. Results Altogether, 1334 venous thromboembolism cases occurred during the follow-up period (incidence rate 1.14 per 1000 person-years, 95% confidence interval [CI] 1.08-1.20), with an incidence rate ratio of hormonal contraception vs no hormonal contraception use of 1.42 (95% CI 1.27-1.58). Compared with non-use, starting the use of gestodene and ethinylestradiol (adjusted odds ratio [aOR] 2.85; 95% CI 1.62-5.03), drospirenone and ethinylestradiol (aOR 1.55; 95% CI 0.98-2.44), desogestrel and ethinylestradiol (aOR 1.97; 95% CI 0.99-3.92), and transdermal patch releasing norelgestromin and ethinylestradiol (aOR 5.10; 95% CI 1.12-23.16), as well as continuing the use of gestodene and ethinylestradiol (aOR 2.60; 95% CI 1.61-4.21), drospirenone and ethinylestradiol (aOR 1.55; 95% CI 1.02-2.37), cyproterone-acetate and estrogen/ethinylestradiol (aOR 1.66; 95% CI 1.06-2.61), and vaginal ring releasing etonogestrel and ethinylestradiol (aOR 3.27; 95% CI 1.95-5.48) were associated with venous thromboembolism risk. Regarding the type of estrogen, the highest risk was associated with current use (vs non use in the previous 180 days) of ethinylestradiol-containing preparations (aOR 2.20; 95% CI 1.82-2.65), followed by estradiol-containing preparations (aOR 1.39; 95% CI 1.04-1.87) with no risk for progestin-only hormonal contraception. Current use of estradiol-containing preparations was not associated with venous thromboembolism risk after exclusion of cyproterone-acetate and estrogen/ethinylestradiol (aOR 1.05; 95% CI 0.66-1.66). Conclusions An increased risk of venous thromboembolism is associated with ethinylestradiol-containing combined preparations. The use of estradiol-containing combined preparations confers only a slightly increased risk, possibly driven by cyproterone-containing combined oral contraceptives, whereas the use of progestin-only contraception is not associated with venous thromboembolism.Peer reviewe

Associations between hormonal contraception use, sociodemographic factors and mental health: a nationwide, register-based, matched case–control study

Objectives Sociodemographic and mental health characteristics are associated with contraceptive choices. We aimed to describe the sociodemographic, reproductive and mental health characteristics of all fertile-aged women in Finland who used hormonal contraception (HC) in 2017. Design A nationwide, register-based study. Setting All women living in Finland in 2017; data from the Care Register of Health Care, Medical Birth Register, Population Register Centre, Prescription Centre, Register of Induced Abortions. Participants All women aged 15-49 with one redeemed HC prescription in 2017 (n=294 356), and a same-sized, age-matched and residence-matched, control group of non-users. Outcomes Rates of HC use; associations between HC use and mental disorders, sociodemographic and reproductive characteristics. Results 25.8% of women aged 15-49 years used HC. Women with the lowest socioeconomic levels had lower odds of using HC than women with upper-level statuses (OR, 95% CI students: 0.97, 0.94 to 0.99; entitled to pension: 0.66, 0.63 to 0.69; other: 0.87, 0.85 to 0.89; unknown: 0.90, 0.85 to 0.90). Women with the highest education (secondary: 1.46, 1.43 to 1.48; tertiary: 1.64, 1.58 to 1.70; academic: 1.60, 1.56 to 1.63) and income (second quarter: 1.57, 1.54 to 1.60; third quarter: 1.85, 1.82 to 1.89; fourth quarter: 2.01, 1.97 to 2.06), and unmarried women had higher odds of using HC than women with the lowest education and income levels, and married (0.61, 0.60 to 0.62), divorced (0.86, 0.84 to 0.88), widowed (0.73, 0.65 to 0.83) or other marital status women (0.26, 0.22 to 0.30). Parous women (0.70, 0.69 to 0.71), those with previous induced abortion(s) (0.91, 0.89 to 0.92) or recent eating (0.68, 0.62 to 0.75) or personality (0.89, 0.79 to 0.97) disorders had lower odds of HC use. Absolute risk differences between women with and without mental disorders ranged from 3.1% (anxiety disorders) to 10.1% (eating disorders). Conclusions A quarter of the fertile-aged women use HC in Finland. Sociodemographic disparities persist in relation to HC use, although of small effect size. HC use is less common among women suffering from severe to moderate psychiatric disorders, especially eating disorders.Peer reviewe

Associations between use of psychotropic medications and use of hormonal contraception among girls and women aged 15-49 years in Finland : a nationwide, register-based, matched case-control study

Objectives The relationship between the use of contraception and of psychiatric medications is understudied. We examined whether the current and past use of psychotropic medications is associated with the use and type of hormonal contraception (HC). Design Nationwide register-based matched case-control study. Settings All fertile-aged (15-49 years) girls and women living in Finland in 2017; data from several national registers. Participants 294 356 girls and women with a redeemed prescription of HC in 2017, and their same-sized control group of non-users (n=294 356) identified through the Prescription Centre. Main outcome measures Associations between the use of psychotropic medications and the use of HC, and the type of HC tested in logistic regression models. Results Altogether 19.5% of the HC users, and 18% of the HC non-users received at least one prescription for a psychotropic medication in 2017. Among HC users, the proportions of occasional and regular users of psychotropic medications in 2013-2016 were 4.5% and 14.8%, while among HC non-users the respective figures were 4.3% and 14.6%, respectively. In multivariable logistic regression models both the use of psychotropic medications in 2017, and their occasional or regular use between 2013-2016 were associated with higher odds of HC use, although with small to very small effect sizes (ORs between 1.37 and 1.06 and 95% CIs 1.22 to 1.53, and 1.03 to 1.09, respectively). After adjustment for covariates, when fixed combinations of progestogens and oestrogens for systemic use was the reference category, women using almost any class of psychotropic medications had higher odds of using other types of HC. Conclusions Fertile-aged girls and women with current and past use of psychotropic medications have higher odds of using HC, with a specific pattern in the type of contraceptives used. Further research is warranted to examine whether our observations indicate a reduction of unwanted pregnancies in women with psychiatric disorders.Peer reviewe

Population-level indicators associated with hormonal contraception use : a register-based matched case-control study

Background Monitoring factors related to hormonal contraception (HC) use is essential to evaluating public health strategies and promoting access to contraception. We aimed to examine municipal social and health indicators of HC use at the population level, and to identify patterns of inequality across Finnish municipalities. Methods We identified all women (15-49 years) with a redeemed HC prescription in Finland in 2017 (n = 294,445), and a control group of non-users. Municipal social and health indicators at the population level were retrieved from the nationwide Statistics and Indicator Bank. Differences between the groups across 309 municipalities were calculated, and associations of municipal-specific proportions of HC users with municipal-specific indicators were studied using LASSO (Least Absolute Shrinkage and Selection Operator) models. Results Sociodemographic differences between HC users and non-users were non-homogenous across municipalities. Indicators positively associated with HC use included: larger population and higher proportions of population aged 16-24 years, of household-dwelling units with one person, of persons with higher education, and of divorces among those aged 25-64. Lower HC use was associated with higher proportions of Swedish-speaking population, of those aged 7-15 years, of young people not in education/training, and of household-dwelling units in overcrowded conditions. Lower HC use was also associated with indicators of outpatient and inpatient healthcare, and of municipal finances in welfare and healthcare. Conclusions Sociodemographic differences in relation to HC use exist across Finnish municipalities. Municipal indicators of social structure, health and welfare, and investment in and use of healthcare services are related to HC use.Peer reviewe

Producing and visualizing a country-wide 3D data repository in Finland

The amount and the quality of 3D spatial data are growing constantly, but the data is collected and stored in a distributed fashion by various data collecting organizations. This may lead to problems regarding interoperability, usability and availability of the data. Traditionally, national spatial data infrastructures have focused on 2D data, but recently there has been great progress towards introducing also 3D spatial data in governmental services. This paper studies the process of creating a country-wide 3D data repository in Finland and visualizing it for the public by using an open source map application. The 3D spatial data is collected and stored into one national topographic database that provides information for the whole society. The data quality control process is executed with an automated data quality module as a part of the import process to the database. The 3D spatial data is served from the database for the visualization via 3D service and the visualization is piloted in the National Geoportal

Metabolomics profile of 5649 users and nonusers of hormonal intrauterine devices in Finland

Publisher Copyright: © 2022 The Author(s)Background: Use of hormonal intrauterine devices has grown during the last decades. Although hormonal intrauterine devices act mostly via local effects on the uterus, measurable concentrations of levonorgestrel are absorbed into the systemic circulation. The possible metabolic changes and large-scale biomarker profiles associated with hormonal intrauterine devices have not yet been studied in detail. Objective: To examine through the metabolomics approach the metabolic profile of patients using hormonal intrauterine devices and how this metabolic profile is affected by duration and discontinuation of use. Study Design: The study consisted of cross-sectional analyses of 5 population-based surveys (FINRISK and FinHealth studies), spanning from 1997 to 2017. All fertile-aged participants (18–49 years) in the surveys with available information on hormonal contraceptive use and metabolomics data (n=5649) were included in the study. Altogether, 211 metabolic measures of users of hormonal intrauterine devices (n=1006) were compared with those of nonusers of hormonal contraception (n=4643) via multivariable linear regression models. To allow comparison across multiple measures, association magnitudes were reported in standard deviation units of difference in biomarker concentration compared with the reference group. Results: After adjustment for covariates, levels of 141 metabolites differed in current users of hormonal intrauterine devices compared with nonusers of hormonal contraception (median difference in biomarker concentration, 0.09 standard deviation): lower levels of particle concentration of larger lipoprotein subclasses, triglycerides, cholesterol and derivatives, apolipoproteins A and B, fatty acids, glycoprotein acetyls, and aromatic amino acids. The metabolic pattern of hormonal intrauterine device use did not change according to duration of use. When comparing previous users and never-users of hormonal intrauterine devices, no significant metabolic differences were observed. Conclusion: The use of hormonal intrauterine devices was associated with several moderate metabolic changes previously associated with reduced arterial cardiometabolic risk. The metabolic effects were independent of duration of use of the hormonal intrauterine devices. Moreover, the metabolic profiles were similar after discontinuation of hormonal intrauterine device use and in never-users.Peer reviewe

Structural validity of the Finnish Manchester-Oxford Foot Questionnaire (MOXFQ) using the Rasch model

Background: The 16-item patient-reported Manchester-Oxford Foot Questionnaire (MOXFQ) with subscales of pain, social interactions, and walking/standing has been claimed for strongest scientific evidence in measuring foot and ankle complaints. This study tests the validity of the Finnish MOXFQ for orthopaedic foot and ankle population using the Rasch analysis. Methods: We translated the MOXFQ into Finnish and used that translation in our study. MOXFQ scores were obtained from 183 patients. Response category distribution, item fit, coverage, targeting, item dependency, ability to measure latent trait (unidimensionality), internal consistency (Cronbach's alpha), and person separation index (PSI) were analyzed. Results: Fifteen of the items had ordered response categories and/or sufficient fit statistics. The subscales provided coverage and targeting. Some residual correlation was noted. Removing one item in the pain subscale led to a unidimensional structure. Alphas and PSIs ranged between 0.68-0.90 and 0.67-0.92, respectively. Conclusions: Despite some infractions of the Rasch model, the instrument functioned well. The subscales of the MOXFQ are meaningful for assessing patient-reported complaints and outcomes in orthopaedic foot and ankle population. (C) 2020 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Validity of five foot and ankle specific electronic patient-reported outcome (ePRO) instruments in patients undergoing elective orthopedic foot or ankle surgery

Background: Patient-reported outcomes (PROS) are widely accepted measures for evaluating outcomes of surgical interventions. As patient-reported information is stored in electronic health records, it is essential that there are valid electronic PRO (ePRO) instruments available for clinicians and researchers. The aim of this study was to evaluate the validity of electronic versions of five widely used foot and ankle specific PRO instruments. Methods: Altogether 111 consecutive elective foot/ankle surgery patients were invited face-to-face to participate in this study. Patients completed electronic versions of the Foot and Ankle Ability Measure (FAAM), the Foot and Ankle Outcome Score (FAOS), the modified Lower Extremity Function Scale (LEFS), the Manchester-Oxford Foot Questionnaire (MOXFQ), and the Visual Analogue Scale Foot and Ankle (VAS-FA) on the day of elective foot and/or ankle surgery. Construct validity, coverage, and targeting of the scales were assessed. Results: Based on general and predefined thresholds, construct validity, coverage, and targeting of the ePRO versions of the FAAM, the FAOS, the MOXFQ, and the VAS-FA were acceptable. Major issues arose with score distribution and convergent validity of the modified LEFS instrument. Conclusions: The ePRO versions of the FAAM, the FAOS, the MOXFQ and the VAS-FA provide valid scores for foot and ankle patients. However, our findings do not support the use of the modified LEFS as an electronic outcome measure for patients with orthopedic foot and/or ankle pathologies. (C) 2020 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.Peer reviewe