Mightyl: A compositional translation from mitl to timed automata

Metric Interval Temporal Logic (MITL) was first proposed in the early 1990s as a specification formalism for real-time systems. Apart from its appealing intuitive syntax, there are also theoretical evidences that make MITL a prime real-time counterpart of Linear Temporal Logic (LTL). Unfortunately, the tool support for MITL verification is still lacking to this day. In this paper, we propose a new construction from MITL to timed automata via very-weak one-clock alternating timed automata. Our construction subsumes the well-known construction from LTL to Büchi automata by Gastin and Oddoux and yet has the additional benefits of being compositional and integrating easily with existing tools. We implement the construction in our new tool MightyL and report on experiments using Uppaal and LTSmin as back-ends

Interrupt Timed Automata: verification and expressiveness

We introduce the class of Interrupt Timed Automata (ITA), a subclass of hybrid automata well suited to the description of timed multi-task systems with interruptions in a single processor environment. While the reachability problem is undecidable for hybrid automata we show that it is decidable for ITA. More precisely we prove that the untimed language of an ITA is regular, by building a finite automaton as a generalized class graph. We then establish that the reachability problem for ITA is in NEXPTIME and in PTIME when the number of clocks is fixed. To prove the first result, we define a subclass ITA- of ITA, and show that (1) any ITA can be reduced to a language-equivalent automaton in ITA- and (2) the reachability problem in this subclass is in NEXPTIME (without any class graph). In the next step, we investigate the verification of real time properties over ITA. We prove that model checking SCL, a fragment of a timed linear time logic, is undecidable. On the other hand, we give model checking procedures for two fragments of timed branching time logic. We also compare the expressive power of classical timed automata and ITA and prove that the corresponding families of accepted languages are incomparable. The result also holds for languages accepted by controlled real-time automata (CRTA), that extend timed automata. We finally combine ITA with CRTA, in a model which encompasses both classes and show that the reachability problem is still decidable. Additionally we show that the languages of ITA are neither closed under complementation nor under intersection

Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification.

There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease

Duloxetine in the treatment of major depressive disorder: an open-label study

<p>Abstract</p> <p>Background</p> <p>Major depressive disorder (MDD) is a chronic and highly disabling condition. Existing pharmacotherapies produce full remission in only 30% to 40% of treated patients. Antidepressants exhibiting dual reuptake inhibition of both serotonin (5-HT) and norepinephrine (NE) may achieve higher rates of remission compared with those acting upon a single neurotransmitter. In this study, the safety and efficacy of duloxetine, a potent dual reuptake inhibitor of 5-HT and NE, were examined.</p> <p>Methods</p> <p>Patients (N = 533) meeting DSM-IV criteria for MDD received open-label duloxetine (60 mg once a day [QD]) for 12 weeks during the initial phase of a relapse prevention trial. Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD₁₇) total score ≥18 and a Clinical Global Impression of Severity (CGI-S) score ≥4 at baseline. Efficacy measures included the HAMD₁₇total score, HAMD₁₇subscales, the CGI-S, the Patient Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for pain, and the Symptom Questionnaire, Somatic Subscale (SQ-SS). Quality of life was assessed using the Sheehan Disability Scale (SDS) and the Quality of Life in Depression Scale (QLDS). Safety was evaluated by recording spontaneously-reported treatment-emergent adverse events, changes in vital signs and laboratory analytes, and the Patient Global Impression of Sexual Function (PGI-SF) scale.</p> <p>Results</p> <p>The rate of discontinuation due to adverse events was 11.3%. Treatment-emergent adverse events reported by ≥10% duloxetine-treated patients were nausea, headache, dry mouth, somnolence, insomnia, and dizziness. Following 12 weeks of open-label duloxetine therapy, significant improvements were observed in all assessed efficacy and quality of life measures. In assessments of depression severity (HAMD₁₇, CGI-S) the magnitude of symptom improvement continued to increase at each study visit, while for painful physical symptoms the onset of improvement was rapid and reached a maximum after 2 to 3 weeks of treatment.</p> <p>Conclusion</p> <p>In this open-label phase of a relapse prevention study, duloxetine (60 mg QD) was shown to be safe and effective in the treatment of MDD.</p> <p>Trial registration</p> <p>NCT00036309.</p

Preliminary Clinical Evaluation of Short Fiber-Reinforced Composite Resin in Posterior Teeth: 12-Months Report

This preliminary clinical trial evaluated 12 month clinical performance of novel filling composite resin system which combines short fiber-reinforced composite resin and conventional particulate filler composite resin in high stress bearing applications. A total of 37 class I and II restorations (compound and complex type) were placed in 6 premolars and 31 molars. The restorations were reviewed clinically at 6 months (baseline) and 12 months using modified USPHS codes change criteria for marginal adaptation, post-operative sensitivity, pulpal pain and secondary caries criteria. Photographs and x-rays were obtained for restorative analysis. Results of 12 months evaluation showed 5 restorations having little marginal leakage (B score) and 1 patient had minor pulpal symptom and post-operative sensitivity (B score). No secondary caries or bulk fracture was detected. The majority of restorations exhibited A scores of the evaluated criteria. After 12 months, restorations combining base of short fiber reinforced composite resin as substructure and surface layer of hybrid composite resin displayed promising performance in high load bearing areas

Image perception and interpretation of abnormalities; can we believe our eyes? Can we do something about it?

The radiologist’s visual impression of images is transmitted, via non-visual means (the report), to the clinician. There are several complex steps from the perception of the images by the radiologist to the understanding of the impression by the clinician. With a process as complex as this, it is no wonder that errors in perception, cognition, interpretation, transmission and understanding are very common. This paper reviews the processes of perception and error generation and possible strategies for minimising them

Evolution of Streptococcus pneumoniae and Its Close Commensal Relatives

Streptococcus pneumoniae is a member of the Mitis group of streptococci which, according to 16S rRNA-sequence based phylogenetic reconstruction, includes 12 species. While other species of this group are considered prototypes of commensal bacteria, S. pneumoniae is among the most frequent microbial killers worldwide. Population genetic analysis of 118 strains, supported by demonstration of a distinct cell wall carbohydrate structure and competence pheromone sequence signature, shows that S. pneumoniae is one of several hundred evolutionary lineages forming a cluster separate from Streptococcus oralis and Streptococcus infantis. The remaining lineages of this distinct cluster are commensals previously collectively referred to as Streptococcus mitis and each represent separate species by traditional taxonomic standard. Virulence genes including the operon for capsule polysaccharide synthesis and genes encoding IgA1 protease, pneumolysin, and autolysin were randomly distributed among S. mitis lineages. Estimates of the evolutionary age of the lineages, the identical location of remnants of virulence genes in the genomes of commensal strains, the pattern of genome reductions, and the proportion of unique genes and their origin support the model that the entire cluster of S. pneumoniae, S. pseudopneumoniae, and S. mitis lineages evolved from pneumococcus-like bacteria presumably pathogenic to the common immediate ancestor of hominoids. During their adaptation to a commensal life style, most of the lineages gradually lost the majority of genes determining virulence and became genetically distinct due to sexual isolation in their respective hosts