Incremental, Inductive Coverability

We give an incremental, inductive (IC3) procedure to check coverability of well-structured transition systems. Our procedure generalizes the IC3 procedure for safety verification that has been successfully applied in finite-state hardware verification to infinite-state well-structured transition systems. We show that our procedure is sound, complete, and terminating for downward-finite well-structured transition systems---where each state has a finite number of states below it---a class that contains extensions of Petri nets, broadcast protocols, and lossy channel systems. We have implemented our algorithm for checking coverability of Petri nets. We describe how the algorithm can be efficiently implemented without the use of SMT solvers. Our experiments on standard Petri net benchmarks show that IC3 is competitive with state-of-the-art implementations for coverability based on symbolic backward analysis or expand-enlarge-and-check algorithms both in time taken and space usage.Comment: Non-reviewed version, original version submitted to CAV 2013; this is a revised version, containing more experimental results and some correction

Approaching the Coverability Problem Continuously

The coverability problem for Petri nets plays a central role in the verification of concurrent shared-memory programs. However, its high EXPSPACE-complete complexity poses a challenge when encountered in real-world instances. In this paper, we develop a new approach to this problem which is primarily based on applying forward coverability in continuous Petri nets as a pruning criterion inside a backward coverability framework. A cornerstone of our approach is the efficient encoding of a recently developed polynomial-time algorithm for reachability in continuous Petri nets into SMT. We demonstrate the effectiveness of our approach on standard benchmarks from the literature, which shows that our approach decides significantly more instances than any existing tool and is in addition often much faster, in particular on large instances.Comment: 18 pages, 4 figure

Preventie van valincidenten bij thuiswonende ouderen: een kostenbesparende interventie?

Nationale en internationale cijfers tonen aan dat 1 op 3 thuiswonende 65-plussers en nagenoeg de helft van de 80-plussers minstens eenmaal per jaar valt. Bij ongeveer 40% van hen resulteert dit in een letsel. Ongeveer 10% van de valpartijen bij ouderen leidt tot ernstige letsels, waaronder heupfracturen (1-2%), andere fracturen (3-5%) en letsels van de weke delen en hoofdtrauma (5%)

Validation of reference tissue modelling for [11C]flumazenil positron emission tomography following head injury.

OBJECTIVE: [(11)C]Flumazenil ([(11)C]FMZ) positron emission tomography (PET) can be used as a measure of neuronal loss. The purpose of this study was to validate reference tissue kinetic modelling of [(11)C]FMZ PET within a group of patients with head injury. METHODS: Following earlier studies, the pons was used as the reference region. PET scans were performed on 16 controls and 11 patients at least 6 months following injury, each of whom also had arterial blood sampling to provide whole blood and metabolite-corrected plasma input functions. Regional non-displaceable binding potentials (BP(ND)) were calculated from five reference tissue models and compared to BP(ND) from arterial input models. For the patients, the regions included a peri-lesional region of interest (ROI). RESULTS: Total distribution volume of the pons was not significantly different between control and patient groups (P = 0.24). BP(ND) from all the reference tissue approaches correlated well with BP(ND) from the plasma input models for both controls (r (2) = 0.98-1.00; P < 0.001) and patients (r (2) = 0.99-1.00; P < 0.001). For the peri-lesional regions (n = 11 ROI values), the correlation was also high (r (2) = 0.91). CONCLUSIONS: These results indicate that reference tissue modelling with the pons as the reference region is valid for [(11)C]FMZ PET in head-injured patients at 6 months following injury within both normal appearing and peri-lesional brain regions

Use of T2-weighted magnetic resonance imaging of the optic nerve sheath to detect raised intracranial pressure.

INTRODUCTION: The dural sheath surrounding the optic nerve communicates with the subarachnoid space, and distends when intracranial pressure is elevated. Magnetic resonance imaging (MRI) is often performed in patients at risk for raised intracranial pressure (ICP) and can be used to measure precisely the diameter of optic nerve and its sheath. The objective of this study was to assess the relationship between optic nerve sheath diameter (ONSD), as measured using MRI, and ICP. METHODS: We conducted a retrospective blinded analysis of brain MRI images in a prospective cohort of 38 patients requiring ICP monitoring after severe traumatic brain injury (TBI), and in 36 healthy volunteers. ONSD was measured on T2-weighted turbo spin-echo fat-suppressed sequence obtained at 3 Tesla MRI. ICP was measured invasively during the MRI scan via a parenchymal sensor in the TBI patients. RESULTS: Measurement of ONSD was possible in 95% of cases. The ONSD was significantly greater in TBI patients with raised ICP (>20 mmHg; 6.31 +/- 0.50 mm, 19 measures) than in those with ICP of 20 mmHg or less (5.29 +/- 0.48 mm, 26 measures; P < 0.0001) or in healthy volunteers (5.08 +/- 0.52 mm; P < 0.0001). There was a significant relationship between ONSD and ICP (r = 0.71, P < 0.0001). Enlarged ONSD was a robust predictor of raised ICP (area under the receiver operating characteristic curve = 0.94), with a best cut-off of 5.82 mm, corresponding to a negative predictive value of 92%, and to a value of 100% when ONSD was less than 5.30 mm. CONCLUSIONS: When brain MRI is indicated, ONSD measurement on images obtained using routine sequences can provide a quantitative estimate of the likelihood of significant intracranial hypertension

Inhibitory Control Across the Preschool Years: Developmental Changes and Associations with Parenting

The normative developmental course of inhibitory control between 2.5 and 6.5 years, and associations with maternal and paternal sensitivity and intrusiveness were tested. The sample consisted of 383 children (52.5% boys). During four annual waves, mothers and fathers reported on their children’s inhibitory control using the Children\u27s Behavior Questionnaire. During the first wave, mothers’ and fathers’ sensitivity and intrusiveness were observed and coded with the Emotional Availability Scales. Inhibitory control exhibited partial scalar invariance over time, and increased in a decelerating rate. For both mothers and fathers, higher levels of sensitivity were associated with a higher initial level of children\u27s inhibitory control, whereas higher levels of intrusiveness predicted a slower increase in children\u27s inhibitory control

Dynamic Changes in White Matter Abnormalities Correlate With Late Improvement and Deterioration Following TBI: A Diffusion Tensor Imaging Study.

OBJECTIVE: Traumatic brain injury (TBI) is not a single insult with monophasic resolution, but a chronic disease, with dynamic processes that remain active for years. We aimed to assess patient trajectories over the entire disease narrative, from ictus to late outcome. METHODS: Twelve patients with moderate-to-severe TBI underwent magnetic resonance imaging in the acute phase (within 1 week of injury) and twice in the chronic phase of injury (median 7 and 21 months), with some undergoing imaging at up to 2 additional time points. Longitudinal imaging changes were assessed using structural volumetry, deterministic tractography, voxel-based diffusion tensor analysis, and region of interest analyses (including corpus callosum, parasagittal white matter, and thalamus). Imaging changes were related to behavior. RESULTS: Changes in structural volumes, fractional anisotropy, and mean diffusivity continued for months to years postictus. Changes in diffusion tensor imaging were driven by increases in both axial and radial diffusivity except for the earliest time point, and were associated with changes in reaction time and performance in a visual memory and learning task (paired associates learning). Dynamic structural changes after TBI can be detected using diffusion tensor imaging and could explain changes in behavior. CONCLUSIONS: These data can provide further insight into early and late pathophysiology, and begin to provide a framework that allows magnetic resonance imaging to be used as an imaging biomarker of therapy response. Knowledge of the temporal pattern of changes in TBI patient populations also provides a contextual framework for assessing imaging changes in individuals at any given time point

Successful optic nerve regeneration in the senescent zebrafish despite age-related decline of cell intrinsic and extrinsic response processes

Dysfunction of the central nervous system (CNS) in neurodegenerative diseases or after brain lesions seriously affects life quality of a growing number of elderly, since the adult CNS lacks the capacity to replace or repair damaged neurons. Despite intensive research efforts, full functional recovery after CNS disease and/or injury remains challenging, especially in an aging environment. As such, there is a rising need for an aging model in which the impact of aging on successful regeneration can be studied. Here, we introduce the senescent zebrafish retinotectal system as a valuable model to elucidate the cellular and molecular processes underlying age-related decline in axonal regeneration capacities. We found both intrinsic and extrinsic response processes to be altered in aged fish. Indeed, expression levels of growth-associated genes are reduced in naive and crushed retinas, and the injury-associated increase in innate immune cell density appears delayed, suggesting retinal inflammaging in old fish. Strikingly, however, despite a clear deceleration in regeneration onset and early axon outgrowth leading to an overall slowing of optic nerve regeneration, reinnervation of the optic tectum and recovery of visual function occurs successfully in the aged zebrafish retinotectal system