Timing Analysis using the MARTE Profile in the Design of Rail Automation Systems

International audienceFor dependable systems as in the railway domain the timing behaviour is considered part of the functional correctness. Thus timing requirements have to be traced and refined through the system and software development phases and validation and verification efforts have to address the timing as well as the pure input/output behaviour. We show how timing can be handled in a UML or SysML based approach to the development of software-intensive railway systems by using the new MARTE profile. Thereby timing becomes fully integrated in the chain of system and software models and may benefit from tool support. Moreover, automated timing analysis may be employed via model transformations which enables the exploration of timing-related issues in various design phases

Primary hyperparathyroidism caused by bilateral parathyroid cystic carcinoma in a cat

Abstract Case summary A 16-year-old neutered female Korat cat presented with chronic vomiting, mild azotaemia and mild hypercalcaemia. Physical examination revealed bilateral palpable masses on each side of the trachea. Laboratory results were consistent with primary hyperparathyroidism, diagnostic imaging findings with cystic thyroid or parathyroid masses, and fine-needle aspiration cytology with thyroid hyperplasia or adenoma. In order to confirm whether one or two of the masses were the cause of the hyperparathyroidism, cystic fluid was aspirated from both for parathyroid hormone concentration measurement. The concentration was shown to exceed that of the serum manyfold in both samples, confirming both masses to be functional and of parathyroid origin. A total parathyroidectomy and thyroidectomy were performed on the right side, and a subtotal thyroidectomy and a subtotal to total parathyroidectomy on the left, without any major postoperative complications. Histopathology was consistent with bilateral parathyroid carcinoma. Relevance and novel information To our knowledge, this report is the first to describe a rare case of bilateral parathyroid cystic carcinoma in a cat. It highlights the usefulness of determining parathyroid hormone concentration in the cystic fluid of a suspected neoplastic parathyroid mass preoperatively. It also demonstrates that it may be possible to remove most of the cervical parathyroid and thyroid tissue of a cat without causing any clinically relevant hypocalcaemia or iatrogenic hypothyroidism. However, serum concentrations of ionised calcium, thyroxine and creatinine should be closely monitored in the postoperative period in order to detect and control possible complications.Peer reviewe

A detailed description of two controlled experiments concerning the usefulness of assertions as a means for programming

Assertions or more generally "Programming by contract" have gained widespread acceptance in the computer science community as a means for correct program development. However, the literature lacks an empirically evaluation of the benefits a programmer gains by using assertions in his software development. This paper reports about two controlled experiments to close this gap. Both experiments compared "Programming by contract" to the traditional programming style without assertions. The evaluation suggests that assertions tend to decrease the programming effort and that assertions lead to more reliable programs compared to those programs written without using them

Effects of a glyphosate-based herbicide on soil animal trophic groups and associated ecosystem functioning in a northern agricultural field

Despite an increasing concern of consequences of using vast amounts of glyphosate-based herbicides in agroecosystems, their potential effects on non-target soil organisms and soil functioning are mostly unknown. It has also been argued that fields in northern latitudes should be under special surveillance as the short active period of decomposers may restrict glyphosate degradation. We investigated the effects of a glyphosate- based herbicide, Roundup, on the abundance of enchytraeids and nematodes, both essential groups in decomposer food webs, and plant litter mass loss and soil availability of mineral N in a two-year agricultural field setting in south-west Finland. Our experiment consisted of (1) non-treated weed plots, (2) plots, where weeds were killed by hoeing, and (3) plots treated with both Roundup and hoeing. We found that killing plants by hoeing had drastic effects on soil fauna and functioning, and apparently, distinguishing these effects from direct glyphosate effects is profoundly important when evaluating glyphosate risks in soils. In contrast, the effects of Roundup on soil fauna and functioning were minor and transient and no glyphosate remains were found in the soil at the end of the experiment. These results suggest that side-effects can be minor and glyphosate degradation effective also in soil under northern climatic conditions

Relationships between geomagnetic Ар-indeх and parameters of the immunity in patients with neuroendocrine-immune complex dysfunction in former sportsmen

Background. The effect of geomagnetism on human immunity has so far been studied through long-term observations. Recently, we have been detected the immediate immunotropic effects of the disturbances of the geomagnetic field (Ap-index) at multiple sclerosis patients. The aim of this study was to identify the immunotropic effects of geomagnetism on another contingent of people. Material and methods. The object of observation were 21 men (24-63 y) and 20 women (33-62 y) with neuroendocrine-immune complex dysfunction. Each patient was tested twice with an interval of 4 days. Observations were carried out on 09.06. and 13.06. 2015, 14.09 and 18.09. 2015, 27-28.03. and 04-05.04. 2018, 28.01. and 01.02. 2019. Retrospectively we recorded the geomagnetic Ap-Index on the day of testing and during the previous 7 days, using resource https://www.spaceweatherlive.com/. The content of subpopulations of lymphocytes expressing CD3, CD4, CD25, CD8, CD22 and CD56 receptors as well as the serum concentration of circulating immune complexes, immunoglobulins classes M, G, A, C-reactive protein and IL-1β was determined. The state of phagocytic function of neutrophils estimated by microbial count and phagocytic and killing indices against Staphylococcus aureus and Escherichia coli. Results. During the week, the average level of Ap-index ranged from 7 to 13 nT. Maximum coefficients of multiple correlation with immunity parameters were detected for Ap-index on the eve of blood sampling (R=0,768) and 5 days before it (R=0,758) while the minimum on 3 (R=0,541) and 2 (R=0,479) days before sampling. The canonical correlation between Ap-indices for 7 days before and on the day of testing, on the one hand, and the immunity parameters - on the other hand, was very strong: R=0,921; R2=0,849; χ2(200)=375; p<10-6. Conclusion. Disturbances of the geomagnetic field (Ap-index) has a significant immediate modulating effect on the immune parameters, mostly phagocytosis completeness, Igg A and M serum concentration, T-helper and B lymphocytes as well as eosinophils, rod-shaped neutrophils and monocytes blood level

Assessing toxicity of metal contaminated soil from glassworks sites with a battery of biotests

© 2017 The present study addresses toxicological properties of metal contaminated soils, using glassworks sites in south-eastern Sweden as study objects. Soil from five selected glassworks sites as well as from nearby reference areas were analysed for total and water-soluble metal concentrations and general geochemical parameters. A battery of biotests was then applied to assess the toxicity of the glassworks soil environments: a test of phytotoxicity with garden cress (Lepidium sativum); the BioTox™ test for toxicity to bacteria using Vibrio fischeri; and analyses of abundancies and biomass of nematodes and enchytraeids. The glassworks- and reference areas were comparable with respect to pH and the content of organic matter and nutrients (C, N, P), but total metal concentrations (Pb, As, Ba, Cd and Zn) were significantly higher at the former sites. Higher metal concentrations in the water-soluble fraction were also observed, even though these concentrations were low compared to the total ones. Nevertheless, toxicity of the glassworks soils was not detected by the two ex situ tests; inhibition of light emission by V. fischeri could not be seen, nor was an effect seen on the growth of L. sativum. A decrease in enchytraeid and nematode abundance and biomass was, however, observed for the landfill soils as compared to reference soils, implying in situ toxicity to soil-inhabiting organisms. The confirmation of in situ bioavailability and negative effects motivates additional studies of the risk posed to humans of the glassworks villages

A First-in-Human Study of Novel Cereblon Modulator Avadomide (CC-122) in Advanced Malignancies.

Purpose Avadomide is a novel, small-molecule therapeutic agent that modulates cereblon E3 ligase activity and exhibits potent antitumor and immunomodulatory activities. This first-in-human phase I study (NCT01421524) evaluated the safety and clinical activity of avadomide in patients with advanced solid tumors, non-Hodgkin lymphoma (NHL), and multiple myeloma.Patients and methods Thirty-four patients were treated with avadomide in 7 dose-escalation cohorts using a 3 + 3 design (0.5-3.5 mg, 28-day continuous dosing cycles). The primary objectives were to determine the dose-limiting toxicity (DLT), nontolerated dose (NTD), maximum tolerated dose (MTD), recommended phase II dose, and pharmacokinetics of avadomide. The secondary objective was to determine preliminary avadomide efficacy. Exploratory objectives included evaluation of pharmacodynamic effects of avadomide.Results DLTs were reported in 2 patients, and grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 14 patients (41%). The most common TEAEs (≥15%) were fatigue, neutropenia, and diarrhea. The NTD and MTD were 3.5 and 3.0 mg, respectively. Of 5 patients with NHL, 1 achieved a complete response, and 2 had partial responses. Although no objective responses were observed in patients with solid tumors, 5 of 6 patients with brain cancer experienced nonprogression of ≥6 months. A dose-dependent relationship between Aiolos degradation in peripheral B and T cells occurred within 5 hours of the first dose of avadomide administered, starting at 0.5 mg.Conclusions Avadomide monotherapy demonstrated acceptable safety and favorable pharmacokinetics in patients with solid tumors, NHL, and multiple myeloma. In addition, 3 objective responses were observed in NHL