Metric Semantics and Full Abstractness for Action Refinement and Probabilistic Choice

This paper provides a case-study in the field of metric semantics for probabilistic programming. Both an operational and a denotational semantics are presented for an abstract process language L_pr, which features action refinement and probabilistic choice. The two models are constructed in the setting of complete ultrametric spaces, here based on probability measures of compact support over sequences of actions. It is shown that the standard toolkit for metric semantics works well in the probabilistic context of L_pr, e.g. in establishing the correctness of the denotational semantics with respect to the operational one. In addition, it is shown how the method of proving full abstraction --as proposed recently by the authors for a nondeterministic language with action refinement-- can be adapted to deal with the probabilistic language L_pr as well

Bisimulation of Labeled State-to-Function Transition Systems of Stochastic Process Languages

Labeled state-to-function transition systems, FuTS for short, admit multiple transition schemes from states to functions of finite support over general semirings. As such they constitute a convenient modeling instrument to deal with stochastic process languages. In this paper, the notion of bisimulation induced by a FuTS is proposed and a correspondence result is proven stating that FuTS-bisimulation coincides with the behavioral equivalence of the associated functor. As generic examples, the concrete existing equivalences for the core of the process algebras ACP, PEPA and IMC are related to the bisimulation of specific FuTS, providing via the correspondence result coalgebraic justification of the equivalences of these calculi.Comment: In Proceedings ACCAT 2012, arXiv:1208.430

Ecologische gevolgen van bollenteelt op de Veluwe : bureaustudie naar omvang bollenteelt, bestrijdingsmiddelengebruik en mogelijke effecten op natuur

Naar aanleiding van een vraag van de Partij voor de Dieren in de Provinciale Staten van Gelderland is een korte bureaustudie uitgevoerd naar de mogelijke ecologische gevolgen van bollenteelt op de Veluwe voor Natura 2000-doelen. De vraagstelling spitste zich toe op een aantal onderdelen: omvang van de bollenteelt op de Veluwe, ontwikkelingstrend van bollenteelt op de Veluwe, verschillen in bestrijdingsmiddelengebruik tussen 'normale' akkerbouw (maïs, aardappelen, graan) en bollenteelt en mogelijke nadelige effecten op aangrenzende natuur via verwaaiing, uitspoeling of anderszins

NK1-r antagonist treatment comparable to decompressive craniectomy in reducing intracranial pressure following stroke

Background and Purpose: The morbidity and early mortality associated with stroke is largely attributable to cerebral edema and elevated intracranial pressure (ICP). Existing pharmacotherapies do not target the underlying pathophysiology and are often ineffective in sustainably lowering ICP, whilst decompressive craniectomy (DC) surgery is life-saving yet with surgical/peri-operative risk and increased morbidity in the elderly. Accordingly, there is an urgent need for therapies that directly target the mechanisms of edema genesis. Neurogenic inflammation, mediated by substance P (SP) binding to the tachykinin NK1 receptor (NK1-r), is associated with blood-brain barrier (BBB) disruption, cerebral edema and poor outcome post-stroke. NK1-r antagonist treatment ameliorates BBB dysfunction and cerebral edema in rodent stroke models. However, treatment has not been investigated in a large animal model, an important step toward clinical translation. Consequently, the current study compared the efficacy of NK1-r antagonist treatment to DC surgery in reducing ICP post-stroke in a clinically relevant ovine model. Methods: Anesthetized female Merino sheep (65 ± 6 kg, 18-24 months) underwent sham surgery (n = 4) or permanent middle cerebral artery occlusion (n = 22). Stroke animals were randomized into one of 5 treatments: 1×NK1 bolus (4 h), 2×NK1 bolus (4 h;9 h), 3×NK1 bolus (4 h;9 h;14 h), DC surgery (performed at 4 h) or saline vehicle. ICP, blood pressure and blood gasses were monitored for 24 h post-stroke. At 24 h post-stroke anesthetized animals underwent MRI followed by perfusion and brains removed and processed for histological assessment. Results: 2×NK1, 3×NK1 administration or DC surgery significantly (p < 0.05) reduced ICP compared to vehicle. 1×NK1 was ineffective in sustainably lowering ICP. On MRI, midline shift and cerebral edema were more marked in vehicles compared to NK1-r treatment groups. Conclusion: Two or three boluses of NK1-r antagonist treatment reduced ICP comparable to DC surgery, suggesting it may provide a novel alternative to invasive surgery for the management of elevated ICP.Annabel J. Sorby-Adams, Anna V. Leonard, Jan W. Hoving, Nawaf Yassi, Robert Vink, Adam J. Wells and Renée J. Turne

23 Questions of fluency in Australian languages revitalisation

Changes in endothelial glycocalyx are one of the earliest changes in development of cardiovascular disease. The endothelial glycocalyx is both an important biological modifier of interactions between flowing blood and the vessel wall, and a determinant of organ perfusion. We hypothesize that deeper penetration of erythrocytes into the glycocalyx is associated with reduced microvascular perfusion. The population-based prospective cohort study (the Netherlands Epidemiology of Obesity [NEO] study) includes 6,673 middle-aged individuals (oversampling of overweight and obese individuals). Within this cohort, we have imaged the sublingual microvasculature of 915 participants using sidestream darkfield (SDF) imaging together with a recently developed automated acquisition and analysis approach. Presence of RBC (as a marker of microvascular perfusion) and perfused boundary region (PBR), a marker for endothelial glycocalyx barrier properties for RBC accessibility, were assessed in vessels between 5 and 25 µm RBC column width. A wide range of variability in PBR measurements, with a mean PBR of 2.14 µm (range: 1.43-2.86 µm), was observed. Linear regression analysis showed a marked association between PBR and microvascular perfusion, reflected by RBC filling percentage (regression coefficient β: -0.034; 95% confidence interval: -0.037 to -0.031). We conclude that microvascular beds with a thick ("healthy") glycocalyx (low PBR), reflects efficient perfusion of the microvascular bed. In contrast, a thin ("risk") glycocalyx (high PBR) is associated with a less efficient and defective microvascular perfusion

Determining the temporal profile of intracranial pressure changes following transient stroke in an ovine model

Cerebral edema and elevated intracranial pressure (ICP) are the leading cause of death in the first week following stroke. Despite this, current treatments are limited and fail to address the underlying mechanisms of swelling, highlighting the need for targeted treatments. When screening promising novel agents, it is essential to use clinically relevant large animal models to increase the likelihood of successful clinical translation. As such, we sought to develop a survival model of transient middle cerebral artery occlusion (tMCAO) in the sheep and subsequently characterize the temporal profile of cerebral edema and elevated ICP following stroke in this novel, clinically relevant model. Merino-sheep (27M;31F) were anesthetized and subject to 2 h tMCAO with reperfusion or sham surgery. Following surgery, animals were allowed to recover and returned to their home pens. At preselected times points ranging from 1 to 7 days post-stroke, animals were re-anesthetized, ICP measured for 4 h, followed by imaging with MRI to determine cerebral edema, midline shift and infarct volume (FLAIR, T2 and DWI). Animals were subsequently euthanized and their brain removed for immunohistochemical analysis. Serum and cerebrospinal fluid samples were also collected and analyzed for substance P (SP) using ELISA. Intracranial pressure and MRI scans were normal in sham animals. Following stroke, ICP rose gradually over time and by 5 days was significantly (p < 0.0001) elevated above sham levels. Profound cerebral edema was observed as early as 2 days post-stroke and continued to evolve out to 6 days, resulting in significant midline shift which was most prominent at 5 days post-stroke (p < 0.01), in keeping with increasing ICP. Serum SP levels were significantly elevated (p < 0.01) by 7 days post-tMCAO. We have successfully developed a survival model of ovine tMCAO and characterized the temporal profile of ICP. Peak ICP elevation, cerebral edema and midline shift occurred at days 5-6 following stroke, accompanied by an elevation in serum SP. Our findings suggest that novel therapeutic agents screened in this model targeting cerebral edema and elevated ICP would most likely be effective when administered prior to 5 days, or as early as possible following stroke onset.Annabel J. Sorby-Adams, Anna V. Leonard, Levi E. Elms, Oana C. Marian, Jan W. Hoving, Nawaf Yassi, Robert Vink, Emma Thornton and Renée J. Turne

Microvascular differences in individuals with obesity at risk of developing cardiovascular disease

Objective This study aimed to investigate microvascular differences in individuals with obesity at risk for developing cardiovascular disease. Methods In this cross-sectional Netherlands Epidemiology of Obesity study, participant sublingual microcirculation was assessed with a newly developed GlycoCheck software (Microvascular Health Solutions Inc., Salt Lake City, Utah), which integrates red blood cell velocity within the smallest capillaries (4-7 mu m) and feed vessels (>10 mu m). Framingham Risk Score was used to calculate 10-year cardiovascular risk, divided into low-, intermediate-, and high-risk groups. ANOVA was used to evaluate microvascular differences among the groups. Results A total of 813 participants were included. The high-risk group (n = 168) was characterized by differences in the microvasculature compared with the low-risk group (n = 392): the high-risk group had a 49% reduction in the number of smallest capillaries and a 9.1-mu m/s (95% CI: 5.2-12.9) higher red blood cell velocity in the feed vessels. No differences in velocity-corrected perfused boundary regions were found. Conclusions It was observed that, with adding red blood cell velocity to the software, sidestream dark field imaging is able to detect microcirculatory differences in a cohort of individuals with obesity at risk for developing cardiovascular disease.Clinical epidemiolog

Monte Carlo Methods for Estimating Interfacial Free Energies and Line Tensions

Excess contributions to the free energy due to interfaces occur for many problems encountered in the statistical physics of condensed matter when coexistence between different phases is possible (e.g. wetting phenomena, nucleation, crystal growth, etc.). This article reviews two methods to estimate both interfacial free energies and line tensions by Monte Carlo simulations of simple models, (e.g. the Ising model, a symmetrical binary Lennard-Jones fluid exhibiting a miscibility gap, and a simple Lennard-Jones fluid). One method is based on thermodynamic integration. This method is useful to study flat and inclined interfaces for Ising lattices, allowing also the estimation of line tensions of three-phase contact lines, when the interfaces meet walls (where "surface fields" may act). A generalization to off-lattice systems is described as well. The second method is based on the sampling of the order parameter distribution of the system throughout the two-phase coexistence region of the model. Both the interface free energies of flat interfaces and of (spherical or cylindrical) droplets (or bubbles) can be estimated, including also systems with walls, where sphere-cap shaped wall-attached droplets occur. The curvature-dependence of the interfacial free energy is discussed, and estimates for the line tensions are compared to results from the thermodynamic integration method. Basic limitations of all these methods are critically discussed, and an outlook on other approaches is given