StringFuzz: A Fuzzer for String SMT Solvers

We introduce StringFuzz, a software tool for automatically testing string SMT solvers. String SMT solvers are specialised software tools for solving the Satisfiability Modulo Theories (SMT) problem with string contraints, which is a type of constraint satisfaction problem applicable in industry. Like all tools, string SMT solvers need testing. The developers of solvers commonly test them with published test suites: pre-generated sets of problem instances (i.e. example problems). As new features are added to string SMT solvers, they often are not exercised by existing suites. We introduce StringFuzz, a tool for solver developers to generate SMT instances to exercise and find defects in their solvers. We describe StringFuzz’s features for generating and transforming SMT instances with string and regex constraints. We also show StringFuzz’s many controls, and show how to use them to generate specially tuned scaling instances. For public use, we present our own suite of StringFuzz-generated SMT instances. We also introduce StringBreak, an automated exploratory tester for string SMT solvers, which uses a genetic algorithm to generate SMT instances that take a long time for solvers to solve. To demonstrate the usefulness of StringFuzz and StringBreak, we show experimental results from testing leading string SMT solvers (Z3str3, CVC4, Z3str2, and Norn) with them. We describe two defects and one potential future enhancement that we discovered in Z3str3 as a result of our experiments

Rheumatoid Meningitis Presenting With Acute Parkinsonism and Protracted Non-convulsive Seizures: An Unusual Case Presentation and Review of Treatment Strategies

Rheumatoid meningitis is a rare complication of rheumatoid arthritis (RA). It is associated with substantial morbidity and mortality. The condition may present in a variety of ways and is therefore diagnostically challenging. Uncertainty still exists regarding the optimal treatment strategy. Herein, we describe the case of a 74-year-old man with a history of well-controlled seropositive RA on low-dose prednisone, hydroxychloroquine, and methotrexate. The patient presented with a several-month history of multiple prolonged episodes of expressive aphasia, right hemiparesis, and encephalopathy. Although no epileptiform activity was recorded on repeated electroencephalography, the symptoms fully resolved following treatment with antiepileptic drugs. He subsequently developed acute asymmetrical parkinsonism of the right hemibody. Magnetic resonance imaging revealed subtle enhancement of the leptomeninges over the left frontoparietal convexity. Cerebrospinal fluid analysis revealed a mild lymphocytic pleocytosis and elevated proteins. Histopathologic analysis of a meningeal biopsy revealed nodular rheumatoid meningitis. The patient was treated with corticosteroids and cyclophosphamide, following which he incompletely recovered. This is the first description of rheumatoid meningitis manifesting with acute parkinsonism and protracted non-convulsive seizures. A summary of cases reported since 2005, including data on pathology, therapy and outcomes, along with a discussion on the efficacy of different treatment strategies are provided

Gestational diabetes as a diabetes risk factor for the child

Gestational diabetes (GDM) is associated with excess weight gain and insulin resistance in offspring. Less is known about the association between GDM and diabetes incidence in youth. While type 2 diabetes (T2D) is the subtype of diabetes most consistently associated with insulin resistance, there is evidence that among those at risk immunologically for type 1 diabetes (T1D), insulin resistance may accelerate or precipitate its manifestation. This MSc Project examined the association between maternal GDM and overall diabetes incidence in adolescents and young adults. A retrospective cohort study was undertaken using both health administrative databases and birth and death registry data from the province of Quebec. Cohort inception was from April 1, 1990 to December 31, 1998, and follow-up from age 12 years to March 31, 2012, the developmental period when insulin resistance typically emerges. Randomly-selected singleton live births between April 1, 1990 and December 31, 1998 complicated by GDM were eligible for inclusion. These were 1:1 matched to those without GDM (i.e., matching by year of delivery, mother's age-group, and health region).The primary exposure was GDM in mothers, defined as one hospital discharge diagnosis and/or two outpatient physician claims for GDM within 6 months of delivery. The primary outcome was incident diabetes in youth, defined as one hospital discharge diagnosis and/or two outpatient visit diagnoses within a 2-year time period. The relationship between GDM status and diabetes in offspring was evaluated through survival analysis (Cox proportional hazard models).A total of 36,762 children were studied (mean birth weight 3,364g (SD 582g) with maternal GDM; 3,342g (SD 556g) without GDM in mothers). In total, 147 children were diagnosed with diabetes between 12 years of age and 2012 (maximum age 22 years).Diabetes incidence in offspring of mothers with GDM was more than twice as high as diabetes incidence in offspring of mothers without GDM, in both unadjusted (HR 2.25, 95% CI 1.56, 3.25) and adjusted models (HR 2.12, 95% CI 1.41, 3.17; with adjustment for sex, gestational age, birth weight, maternal education, ethnocultural origin, maternal age, maternal history of previous pregnancy, and stillbirth) This work conclusively demonstrates that GDM in mothers is associated with diabetes in youth. T1D and T2D cannot be distinguished in health administrative databases in Quebec. Given that T1D represents approximately 90% of diabetes cases in youth, our findings indirectly support the accelerator hypothesis (i.e., T1D develops earlier in a context of insulin resistance). The association between GDM and T2D in youth may be underestimated. In light of its strong association with diabetes in youth and young adulthood, maternal GDM may thus serve as an indicator to guide future strategies aimed at diabetes prevention and early disease detection.Le diabète gestationnel (DG) est associé avec la prise du poids et la résistance à l'insuline chez les progénitures. L'association entre le DG et l'incidence du diabète chez les jeunes est quant à elle moins connue. Tandis que le diabète type 2 (DB2) est le sous-type du diabète le plus régulièrement associé avec la résistance à l'insuline, des preuves démontrent que la résistance à l'insuline peut accélérer ou même précipiter le risque immunologique pour le diabète type 1 (DB1). L'objectif de ce mémoire fut d'examiner l'association entre le DG maternel et l'incidence globale du diabète (DB1 et DB2) chez les adolescents et les jeunes adultes. Une étude de cohorte rétrospective a été réalisée en utilisant à la fois les bases de données médico-administratives et les registres de naissances et décès de la province du Québec. Le début de la cohorte était du 1er avril 1990 au 31 décembre 1998, et l'âge du suivi était de 12 ans au 31 mars 2012, soit la période du développement où la résistance à l'insuline se manifeste typiquement. Des naissances simples sélectionnées aléatoirement entre le 1er avril 1990 et le 31 décembre 1998 compliquées par le DG étaient éligibles à être inclus. Elles étaient appariées selon un rapport 1:1 avec des naissances sans DG (c.-à-d., appariement par l'année de l'accouchement, groupe d'âge des mères et région de santé). L'exposition primaire était le DG chez les mères, défini par un diagnostic-congé et/ou deux réclamations médicales pour le DG à moins de 6 mois après l'accouchement. Le résultat principal était le diabète incident chez les jeunes, défini par un diagnostic-congé et/ou deux visites externes pendant une période de 2 ans. L'association entre le DG et le diabète chez les progénitures a été évaluée par une analyse de survie (modèles des risques proportionnels de Cox). Trente-six mille sept cent soixante-deux enfants ont été évalués (poids moyen à la naissance 3 364g (DS 582g) avec DG maternel, 3 342g (DS 556g) sans DG maternel). En total, 147 enfants ont été diagnostiqués avec le diabète entre l'âge de 12 ans et 2012 (l'âge maximum de 22 ans). L'incidence de diabète chez les progénitures des mères avec le DG était plus que deux fois plus élevée que chez les progénitures des mères sans DG, dans les modelés non-ajustes (IR 2.25, IC 95% 1.56, 3.25) et ajustés (IR 2.12, IC 95% 1.41, 3.17; ajustements pour sexe, âge gestationnel, poids à la naissance, éducation maternelle, origine ethnoculturelle de l'enfant, âge maternel, grossesse antérieure et antécédent de mort-né chez la mère). Cette étude montre d'une manière conclusive que le DG maternel est associé avec le diabète chez les jeunes. On ne peut distinguer le DB1 et le DB2 dans les bases de données administratives québécoises. Étant donné que le DB1 représente environ 90% du diabète chez les jeunes, nos résultats appuient indirectement l'hypothèse d'accélérateur du diabète (c.-à-d., le DB1 se développe plus tôt dans le contexte de la résistance à l'insuline). L'association entre le DG maternel et le DB2 chez les jeunes est possiblement sous-estimée. En tenant compte de l'association forte entre le DG maternel et le diabète chez les jeunes, le DG peut ainsi servir d'indicateur pour guider futures stratégies visant à la prévention du diabète et la détection précoce de cette maladie

Impact of a Local Low-Cost Ward-Based Response System in a Canadian Tertiary Care Hospital

Background. Medical emergency teams (METs) or rapid response teams (RRTs) facilitate early intervention for clinically deteriorating hospitalized patients. In healthcare systems where financial resources and intensivist availability are limited, the establishment of such teams can prove challenging. Objectives. A low-cost, ward-based response system was implemented on a medical clinical teaching unit in a Montreal tertiary care hospital. A prospective before/after study was undertaken to examine the system’s impact on time to intervention, code blue rates, and ICU transfer rates. Results. Ninety-five calls were placed for 82 patients. Median time from patient decompensation to intervention was 5 min (IQR 1–10), compared to 3.4 hours (IQR 0.6–12.4) before system implementation (p<0.001). Total number of ICU admissions from the CTU was reduced from 4.8/1000 patient days (±2.2) before intervention to 3.3/1000 patient days (±1.4) after intervention (IRR: 0.82, p=0.04 (CI 95%: 0.69–0.99)). CTU code blue rates decreased from 2.2/1000 patient days (±1.6) before intervention to 1.2/1000 patient days (±1.3) after intervention (IRR: 0.51, p=0.02 (CI 95%: 0.30–0.89)). Conclusion. Our local ward-based response system achieved a significant reduction in the time of patient decompensation to initial intervention, in CTU code blue rates, and in CTU to ICU transfers without necessitating additional usage of financial or human resources

Metabolic Disease Programming: From Mitochondria to Epigenetics, Glucocorticoid Signalling and Beyond

Embryonic and foetal development are critical periods of development in which several environmental cues determine health and disease in adulthood. Maternal conditions and an unfavourable intrauterine environment impact foetal development and may programme the offspring for increased predisposition to metabolic diseases and other chronic pathologic conditions throughout adult life. Previously, non-communicable chronic diseases were only associated with genetics and lifestyle. Now the origins of non-communicable chronic diseases are associated with early-life adaptations that produce long-term dysfunction. Early-life environment sets the long-term health and disease risk and can span through multiple generations. Recent research in developmental programming aims at identifying the molecular mechanisms responsible for developmental programming outcomes that impact cellular physiology and trigger adulthood disease. The identification of new therapeutic targets can improve offspring's health management and prevent or overcome adverse consequences of foetal programming. This review summarizes recent biomedical discoveries in the Developmental Origins of Health and Disease (DOHaD) hypothesis and highlight possible developmental programming mechanisms, including prenatal structural defects, metabolic (mitochondrial dysfunction, oxidative stress, protein modification), epigenetic and glucocorticoid signalling-related mechanisms suggesting molecular clues for the causes and consequences of programming of increased susceptibility of offspring to metabolic disease after birth. Identifying mechanisms involved in DOHaD can contribute to early interventions in pregnancy or early childhood, to re-set the metabolic homeostasis and break the chain of subsequent events that could lead to the development of disease