Anästhesie und Ahornsirupkrankheit: Fallbericht und perioperatives anästhesiologisches Management

Zusammenfassung: Die Ahornsirupkrankheit ist eine seltene autosomal-rezessive Stoffwechselerkrankung, der eine Störung der Decarboxylierung von verzweigtkettigen Aminosäuren zugrunde liegt. Erste Symptome zeigen sich bereits in der Neonatalperiode. Unbehandelt führt die Erkrankung zu rasch progredienter neurologischer Symptomatik. Während stressvoller Situationen wie Infektionen und Operationen können bei Patienten mit Ahornsirupkrankheit schwere ketoacidotische Zustände mit rapider neurologischer Verschlechterung und Hypoglykämien auftreten. Im vorliegenden Beitrag wird über das perioperative Management bei einem 26-jährigen Mann mit Ahornsirupkrankheit berichtet, ein Überblick über die Erkrankung gegeben, und die anästhesiologischen Implikationen werden diskutier

Whole egg consumption and cortical bone in healthy children

Eggs contain bioactive compounds thought to benefit pediatric bone. This cross-sectional study shows a positive link between childhood egg intake and radius cortical bone. If randomized trials confirm our findings, incorporating eggs into children's diets could have a significant impact in preventing childhood fractures and reducing the risk of osteoporosis. INTRODUCTION: This study examined the relationships between egg consumption and cortical bone in children. METHODS: The cross-sectional study design included 294 9-13-year-old black and white males and females. Three-day diet records determined daily egg consumption. Peripheral quantitative computed tomography measured radius and tibia cortical bone. Body composition and biomarkers of bone turnover were assessed using dual-energy X-ray absorptiometry and ELISA, respectively. RESULTS: Egg intake was positively correlated with radius and tibia cortical bone mineral content (Ct.BMC), total bone area, cortical area, cortical thickness, periosteal circumference, and polar strength strain index in unadjusted models (r = 0.144-0.224, all P < 0.050). After adjusting for differences in race, sex, maturation, fat-free soft tissue mass (FFST), and protein intakes, tibia relationships were nullified; however, egg intake remained positively correlated with radius Ct.BMC (r = 0.138, P = 0.031). Egg intake positively correlated with total body bone mineral density, BMC, and bone area in the unadjusted models only (r = 0.119-0.224; all P < 0.050). After adjusting for covariates, egg intake was a positive predictor of radius FFST (β = 0.113, P < 0.050) and FFST was a positive predictor of Ct.BMC (β = 0.556, P < 0.050) in path analyses. There was a direct influence of egg on radius Ct.BMC (β = 0.099, P = 0.035), even after adjusting for the mediator, FFST (β = 0.137, P = 0.020). Egg intake was positively correlated with osteocalcin in both the unadjusted (P = 0.005) and adjusted (P = 0.049) models. CONCLUSION: If the positive influence of eggs on Ct.BMC observed in this study is confirmed through future randomized controlled trials, whole eggs may represent a viable strategy to promote pediatric bone development and prevent fractures

Probably Safe or Live

This paper presents a formal characterisation of safety and liveness properties \`a la Alpern and Schneider for fully probabilistic systems. As for the classical setting, it is established that any (probabilistic tree) property is equivalent to a conjunction of a safety and liveness property. A simple algorithm is provided to obtain such property decomposition for flat probabilistic CTL (PCTL). A safe fragment of PCTL is identified that provides a sound and complete characterisation of safety properties. For liveness properties, we provide two PCTL fragments, a sound and a complete one. We show that safety properties only have finite counterexamples, whereas liveness properties have none. We compare our characterisation for qualitative properties with the one for branching time properties by Manolios and Trefler, and present sound and complete PCTL fragments for characterising the notions of strong safety and absolute liveness coined by Sistla

CPN Tools 4: Multi-formalism and Extensibility

Abstract. CPN Tools is an advanced tool for editing, simulating, and analyzing colored Petri nets. This paper discusses the fourth major re-lease of the tool, which makes it simple to use the tool for ordinary Petri nets, including adding inhibitor and reset arcs, and PNML export. This version also supports declarative modeling using constraints, and adds an extension framework making it easy for third parties to extend CPN Tools using Java.

Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib

Qualitat de vida relacionada amb la salut; Olaparib; Càncer de pàncreesCalidad de vida relacionada con la salud; Olaparib, Cáncer de páncreasHealth-related quality of life; Olaparib; Pancreatic cancerBackground Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. Patients and methods Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. Results Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [−2.47; 95% confidence interval (CI) −7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (−4.45 points; 95% CI −8.75, −0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). Conclusions HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer.This study was sponsored by AstraZeneca and is part of an alliance between AstraZeneca and MSD (no grant number). This research was funded in part through the NIH/NCI Cancer Center Support Grant P30-17 CA008748

A Logical Verification Methodology for Service-Oriented Computing

We introduce a logical verification methodology for checking behavioural properties of service-oriented computing systems. Service properties are described by means of SocL, a branching-time temporal logic that we have specifically designed to express in an effective way distinctive aspects of services, such as, e.g., acceptance of a request, provision of a response, and correlation among service requests and responses. Our approach allows service properties to be expressed in such a way that they can be independent of service domains and specifications. We show an instantiation of our general methodology that uses the formal language COWS to conveniently specify services and the expressly developed software tool CMC to assist the user in the task of verifying SocL formulae over service specifications. We demonstrate feasibility and effectiveness of our methodology by means of the specification and the analysis of a case study in the automotive domain

EPHA2 mutations with oncogenic characteristics in squamous cell lung cancer and malignant pleural mesothelioma.

Squamous cell carcinoma (SCC) and malignant pleural mesothelioma (MPM) are thoracic malignancies with very poor prognosis and limited treatment options. It is an established fact that most of the solid tumors have overexpression of EPHA2 receptor tyrosine kinase. EPHA2 is known to exhibit opposing roles towards cancer progression. It functions in inhibiting cancer survival and migration via a ligand and tyrosine kinase dependent signaling (Y772). Whereas it is known to promote tumor progression and cell migration through a ligand-independent signaling (S897). We analyzed the expression profile and mutational status of the ephrin receptor A2 (EPHA2) in SCC and MPM cell lines and primary patient specimens. The EPHA2 receptor was found to be either overexpressed, mutated or amplified in SCC and MPM. In particular, the EPHA2 mutants A859D and T647M were interesting to explore, A859D Y772 dead mutant exhibited lower levels of phosphorylation at Y772 compared to T647M mutant. Molecular Dynamics simulations studies suggested that differential changes in conformation might form the structural basis for differences in the level of EPHA2 activation. Consequently, A859D mutant cells exhibited increased proliferation as well as cell migration compared to controls and T647M mutant. Kinomics analysis demonstrated that the STAT3 and PDGF pathways were upregulated whereas signaling through CBL was suppressed. Considered together, the present work has uncovered the oncogenic characteristics of EPHA2 mutations in SSC and MPM reinstating the dynamics of different roles of EPHA2 in cancer. This study also suggests that a combination of doxazosin and other EPHA2 inhibitors directed to inhibit the pertinent signaling components may be a novel therapeutic strategy for MPM and Non-small cell lung cancer patients who have either EPHA2 or CBL alterations