Talking quiescence: a rigorous theory that supports parallel composition, action hiding and determinisation

The notion of quiescence - the absence of outputs - is vital in both behavioural modelling and testing theory. Although the need for quiescence was already recognised in the 90s, it has only been treated as a second-class citizen thus far. This paper moves quiescence into the foreground and introduces the notion of quiescent transition systems (QTSs): an extension of regular input-output transition systems (IOTSs) in which quiescence is represented explicitly, via quiescent transitions. Four carefully crafted rules on the use of quiescent transitions ensure that our QTSs naturally capture quiescent behaviour. We present the building blocks for a comprehensive theory on QTSs supporting parallel composition, action hiding and determinisation. In particular, we prove that these operations preserve all the aforementioned rules. Additionally, we provide a way to transform existing IOTSs into QTSs, allowing even IOTSs as input that already contain some quiescent transitions. As an important application, we show how our QTS framework simplifies the fundamental model-based testing theory formalised around ioco.Comment: In Proceedings MBT 2012, arXiv:1202.582

Test Model Coverage Analysis under Uncertainty

In model-based testing (MBT) we may have to deal with a non-deterministic model, e.g. because abstraction was applied, or because the software under test itself is non-deterministic. The same test case may then trigger multiple possible execution paths, depending on some internal decisions made by the software. Consequently, performing precise test analyses, e.g. to calculate the test coverage, are not possible. This can be mitigated if developers can annotate the model with estimated probabilities for taking each transition. A probabilistic model checking algorithm can subsequently be used to do simple probabilistic coverage analysis. However, in practice developers often want to know what the achieved aggregate coverage, which unfortunately cannot be re-expressed as a standard model checking problem. This paper presents an extension to allow efficient calculation of probabilistic aggregate coverage, and moreover also in combination with k-wise coverage

Autoimmune hepatitis displays distinctively high multi-antennary sialylation on plasma N-glycans compared to other liver diseases

BackgroundChanges in plasma protein glycosylation are known to functionally affect proteins and to associate with liver diseases, including cirrhosis and hepatocellular carcinoma. Autoimmune hepatitis (AIH) is a liver disease characterized by liver inflammation and raised serum levels of IgG, and is difficult to distinguish from other liver diseases. The aim of this study was to examine plasma and IgG-specific N-glycosylation in AIH and compare it with healthy controls and other liver diseases.MethodsIn this cross-sectional cohort study, total plasma N-glycosylation and IgG Fc glycosylation analysis was performed by mass spectrometry for 66 AIH patients, 60 age- and sex-matched healthy controls, 31 primary biliary cholangitis patients, 10 primary sclerosing cholangitis patients, 30 non-alcoholic fatty liver disease patients and 74 patients with viral or alcoholic hepatitis. A total of 121 glycans were quantified per individual. Associations between glycosylation traits and AIH were investigated as compared to healthy controls and other liver diseases.ResultsGlycan traits bisection (OR: 3.78 [1.88–9.35], p-value: 5.88 × 10− 3), tetraantennary sialylation per galactose (A4GS) (OR: 2.88 [1.75–5.16], p-value: 1.63 × 10− 3), IgG1 galactosylation (OR: 0.35 [0.2–0.58], p-value: 3.47 × 10− 5) and hybrid type glycans (OR: 2.73 [1.67–4.89], p-value: 2.31 × 10− 3) were found as discriminators between AIH and healthy controls. High A4GS differentiated AIH from other liver diseases, while bisection associated with cirrhosis severity.ConclusionsCompared to other liver diseases, AIH shows distinctively high A4GS levels in plasma, with potential implications on glycoprotein function and clearance. Plasma-derived glycosylation has potential to be used as a diagnostic marker for AIH in the future. This may alleviate the need for a liver biopsy at diagnosis. Glycosidic changes should be investigated further in longitudinal studies and may be used for diagnostic and monitoring purposes in the future.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Assessing the Impacts of Global Warming on Snowpack in the Washington Cascades

The decrease in mountain snowpack associated with global warming is difficult to estimate in the presence of the large year-to-year natural variability in observations of snow-water equivalent (SWE). A more robust approach for inferring the impacts of global warming is to estimate the temperature sensitivity (λ) of spring snowpack and multiply it by putative past and future temperature rises observed across the Northern Hemisphere. Estimates of λ can be obtained from (i) simple geometric considerations based on the notion that as the seasonal-mean temperature rises by the amount δT, the freezing level and the entire snowpack should rise by the increment δT/Γ, where Γ is the mean lapse rate; (ii) the regression of 1 April SWE measurements upon mean winter temperatures; (iii) a hydrological model forced by daily temperature and precipitation observations; and (iv) the use of inferred accumulated snowfall derived from daily temperature and precipitation data as a proxy for SWE. All four methods yield an estimated sensitivity of 20% of spring snowpack lost per degree Celsius temperature rise. The increase of precipitation accompanying a 1°C warming can be expected to decrease the sensitivity to 16%. Considering observations of temperature rise over the Northern Hemisphere, it is estimated that spring snow-water equivalent in the Cascades portion of the Puget Sound drainage basin should have declined by 8%–16% over the past 30 yr resulting from global warming, and it can be expected to decline by another 11%–21% by 2050. These losses would be statistically undetectable from a trend analysis of the region’s snowpack over the past 30 yr.Keywords: Climate change, Snowpack, Mountain meteorology, Pacific decadal oscillatio

Bounded Model Checking for Parametric Timed Automata

Abstract. The paper shows how bounded model checking can be ap-plied to parameter synthesis for parametric timed automata with con-tinuous time. While it is known that the general problem is undecidable even for reachability, we show how to synthesize a part of the set of all the parameter valuations under which the given property holds in a model. The results form a complete theory which can be easily applied to parametric verification of a wide range of temporal formulae – we present such an implementation for the existential part of CTL −X. 1 Introduction and related work The growing abundance of complex systems in real world, and their presence in critical areas fuels the research in formal specification and analysis. One of the established methods in systems verification is model checking, where the system is abstracted into the algebraic model (e.g. various versions of Kripke structures

Implants in the severely resorbed mandibles: whether or not to augment? What is the clinician’s preference?

Contains fulltext : 96000.pdf (publisher's version ) (Open Access)INTRODUCTION: The aim of this study is to inventory in the Netherlands which therapy is the clinician's first choice when restoring the edentulous mandible. MATERIAL AND METHODS: A questionnaire was sent to all Dutch Oral and Maxillofacial surgeons. As part of this, the surgeons were invited to treat five virtual edentulous patients, differing only in mandibular residual height. RESULTS: In cases of a sufficient residual height of 15 mm, all surgeons were in favour to insert solely two implants to anchor an overdenture. In case of a residual height of 12 mm, 10% of the surgeons choose for an augmentation procedure. If a patient was presented with a mandibular height of 10 mm, already 40% of the OMF surgeons executed an augmentation procedure. Most (80%) surgeons prefer the (anterior) iliac crest as donor site. The choice of 'whether or not to augment' was not influenced by the surgeon's age; however, the hospital, where he was trained, did. Surgeons trained in Groningen were more in favour of installing short implants in mandibles with reduced vertical height. DISCUSSION: As the option overdenture supported on two interforaminal implants is reimbursed by the Dutch health assurance, this treatment modality is very popular in the Netherlands. From a point of costs and to minimize bypass comorbidity, surgeons should be more reluctant in executing augmentation procedures to restore the resorbed edentulous mandible as it is dated in literature that also in mandibles with a residual height of 10 mm or less, solely placing implants, thus without an augmentation procedure in advance, is a reliable treatment option

Protein-losing gastroenteropathy: Concepts derived from lymphangiography

Lymphangiograms in 2 patients with protein-losing gastroenteropathy showed abnormalities of both abdominal and lower-extremity lymphatics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44359/1/10620_2005_Article_BF02237631.pd

Impact of model improvements on 80 m wind speeds during the second Wind Forecast Improvement Project (WFIP2)

During the second Wind Forecast Improvement Project (WFIP2; October 2015&ndash;March 2017, held in the Columbia River Gorge and Basin area of eastern Washington and Oregon states), several improvements to the parameterizations used in the High Resolution Rapid Refresh (HRRR &ndash; 3&thinsp;km horizontal grid spacing) and the High Resolution Rapid Refresh Nest (HRRRNEST &ndash; 750&thinsp;m horizontal grid spacing) numerical weather prediction (NWP) models were tested during four 6-week reforecast periods (one for each season). For these tests the models were run in control (CNT) and experimental (EXP) configurations, with the EXP configuration including all the improved parameterizations. The impacts of the experimental parameterizations on the forecast of 80&thinsp;m wind speeds (wind turbine hub height) from the HRRR and HRRRNEST models are assessed, using observations collected by 19 sodars and three profiling lidars for comparison. Improvements due to the experimental physics (EXP vs. CNT runs) and those due to finer horizontal grid spacing (HRRRNEST vs. HRRR) and the combination of the two are compared, using standard bulk statistics such as mean absolute error (MAE) and mean bias error (bias). On average, the HRRR 80&thinsp;m wind speed MAE is reduced by 3&thinsp;%&ndash;4&thinsp;% due to the experimental physics. The impact of the finer horizontal grid spacing in the CNT runs also shows a positive improvement of 5&thinsp;% on MAE, which is particularly large at nighttime and during the morning transition. Lastly, the combined impact of the experimental physics and finer horizontal grid spacing produces larger improvements in the 80&thinsp;m wind speed MAE, up to 7&thinsp;%&ndash;8&thinsp;%. The improvements are evaluated as a function of the model's initialization time, forecast horizon, time of the day, season of the year, site elevation, and meteorological phenomena. Causes of model weaknesses are identified. Finally, bias correction methods are applied to the 80&thinsp;m wind speed model outputs to measure their impact on the improvements due to the removal of the systematic component of the errors. </div

Assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial): study protocol for a randomised controlled trial

Background: Currently, the standard therapy for autoimmune hepatitis (AIH) consists of a combination of prednisolone and azathioprine. However, 15% of patients are intolerant to azathioprine which necessitates cessation of azathioprine or changes in therapy. In addition, not all patients achieve complete biochemical response (CR). Uncontrolled data indicate that mycophenolate mofetil (MMF) can induce CR in a majority of patients. Better understanding of first-line treatment and robust evidence from randomised clinical trials are needed. The aim of this study was to explore the potential benefits of MMF as compared to azathioprine, both combined with prednisolone, as induction therapy in a randomised controlled trial in patients with treatment-naive AIH. Method:s: CAMARO is a randomised (1:1), open-label, parallel-group, multicentre superiority trial. All patients with AIH are screened for eligibility. Seventy adult patients with AIH from fourteen centres in the Netherlands and Belgium will be randomised to receive MMF or azathioprine. Both treatment arms will start with prednisolone as induction therapy. The primary outcome is biochemical remission, defined as serum levels of alanine aminotransferase and immunoglobulin G below the upper limit of normal. Secondary outcomes include safety and tolerability of MMF and azathioprine, time to remission, changes in Model For End-Stage Liver Disease (MELD)-score, adverse events, and aspects of quality of life. The study period will last for 24 weeks. Discussion: The CAMARO trial investigates whether treatment with MMF and prednisolone increases the proportion of patients in remission compared with azathioprine and prednisolone as the current standard treatment strategy. In addition, we reflect on the challenges of conducting a randomized trial in rare diseases.Cellular mechanisms in basic and clinical gastroenterology and hepatolog