100 research outputs found
UmwelteinflĂĽsse auf Werkstoffe
The corrosion behavior of different metals commonly used in civil engineering and construction was investigated under outdoor exposure conditions. The exposure sites were chosen at locations of the Swiss National Air Pollution Monitoring Network (NABEL) in different regions of Switzerland,
where the concentrations of different air pollutants and climate data are registered continuously. After different exposure times, a set of test specimens is taken back for gravimetric evaluation of material loss and chemical characterization of corrosion products and deposits. Transmission
and scanning electron microscopy, X-ray diffraction (XRD), and X-ray fluorescence (XRF) were used to characterize corrosion products. Water soluble compounds on the metal surfaces have also been analyzed quantitatively. First results for the exposure period of six months are presented. They
show large differences in corrosion rate and in the amount of corrosive species on the metal surfaces for the different test sites. In some cases a very good correlation to the specific pollution and climate conditions at the particular locations is possible
Ribose supplementation alone or with elevated creatine does not preserve high energy nucleotides or cardiac function in the failing mouse heart
Background: Reduced levels of creatine and total adenine nucleotides (sum of ATP, ADP and AMP) are hallmarks of chronic
heart failure and restoring these pools is predicted to be beneficial by maintaining the diseased heart in a more favourable
energy state. Ribose supplementation is thought to support both salvage and re-synthesis of adenine nucleotides by
bypassing the rate-limiting step. We therefore tested whether ribose would be beneficial in chronic heart failure in control
mice and in mice with elevated myocardial creatine due to overexpression of the creatine transporter (CrT-OE).
Methods and Results: Four groups were studied: sham; myocardial infarction (MI); MI+ribose; MI+CrT-OE+ribose. In a pilot
study, ribose given in drinking water was bioavailable, resulting in a two-fold increase in myocardial ribose-5-phosphate
levels. However, 8 weeks post-surgery, total adenine nucleotide (TAN) pool was decreased to a similar amount (8–14%) in all
infarcted groups irrespective of the treatment received. All infarcted groups also presented with a similar and substantial
degree of left ventricular (LV) dysfunction (3-fold reduction in ejection fraction) and LV hypertrophy (32–47% increased
mass). Ejection fraction closely correlated with infarct size independently of treatment (r2 = 0.63, p<0.0001), but did not
correlate with myocardial creatine or TAN levels.
Conclusion: Elevating myocardial ribose and creatine levels failed to maintain TAN pool or improve post-infarction LV
remodeling and function. This suggests that ribose is not rate-limiting for purine nucleotide biosynthesis in the chronically
failing mouse heart and that alternative strategies to preserve TAN pool should be investigated
Myocardial creatine levels do not influence response to acute oxidative stress in isolated perfused heart
Background: Multiple studies suggest creatine mediates anti-oxidant activity in addition to its established role in cellular
energy metabolism. The functional significance for the heart has yet to be established, but antioxidant activity could
contribute to the cardioprotective effect of creatine in ischaemia/reperfusion injury.
Objectives: To determine whether intracellular creatine levels influence responses to acute reactive oxygen species (ROS)
exposure in the intact beating heart. We hypothesised that mice with elevated creatine due to over-expression of the
creatine transporter (CrT-OE) would be relatively protected, while mice with creatine-deficiency (GAMT KO) would fare
worse.
Methods and Results: CrT-OE mice were pre-selected for creatine levels 20–100% above wild-type using in vivo 1
H–
MRS.
Hearts were perfused in isovolumic Langendorff mode and cardiac function monitored throughout. After 20 min
equilibration, hearts were perfused with either H2O2 0.5 mM (30 min), or the anti-neoplastic drug doxorubicin 15 mM
(100 min). Protein carbonylation, creatine kinase isoenzyme activities and phospho-PKCd expression were quantified in
perfused hearts as markers of oxidative damage and apoptotic signalling. Wild-type hearts responded to ROS challenge
with a profound decline in contractile function that was ameliorated by co-administration of catalase or dexrazoxane as
positive controls. In contrast, the functional deterioration in CrT-OE and GAMT KO hearts was indistinguishable from wildtype
controls, as was the extent of oxidative damage and apoptosis. Exogenous creatine supplementation also failed to
protect hearts from doxorubicin-induced dysfunction.
Conclusions: Intracellular creatine levels do not influence the response to acute ROS challenge in the intact beating heart,
arguing against creatine exerting (patho-)physiologically relevant anti-oxidant activity
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A pragmatic patient-reported outcome strategy for rare disease clinical trials: application of the EORTC item library to myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.
BackgroundNovel, pragmatic, patient-centered strategies are needed to ensure fit-for-purpose patient-reported outcomes (PRO) instruments in clinical trial research for rare diseases such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). The objective of the current study was to select supplemental items to add to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) to ensure content coverage of all important clinical concepts in patients with higher-risk (HR) MDS, low-blast count (LB) AML, and CMML, thus, improving the instrument's ability to detect clinically meaningful treatment benefit for this context of use.MethodsOur mixed methods approach comprised literature review, clinician consultation (n = 3), and qualitative and quantitative analysis of two stages of patient interview data (n = 14, n = 18) to select library bank items to supplement a generic cancer PRO, the EORTC QLQ-C30.ResultsUnique symptom (n = 54) and impact (n = 72) concepts were organized into conceptual frameworks of treatment benefit, compared with EORTC QLQ-C30 items and conceptual gaps identified. Supplemental items (n = 13) addressing those gaps were selected from the EORTC Item Library and tested with patients. Supplemental item endorsement frequencies met World Health Organization Quality of Life criteria, suggesting good targeting and relevance for this sample. However, three supplemental items were confirmed as problematic based upon cognitive debriefing results, and expert clinical consultations. Ultimately, 10 supplemental items (n = 7 symptom; n = 3 impact) were selected for the MDS/AML/CMML context.ConclusionSupplemental items were selected to enhance the conceptual coverage of the EORTC QLQ-C30 in the areas of fatigue, shortness of breath, and functioning
A Self-administered version of the functioning assessment short test for use in population-based studies: A pilot study
Background: The Functioning Assessment Short Test (FAST) is an interviewer-administered scale assessing functional impairment originally developed for psychiatric patients. Objectives: To adapt the FAST for the general population, we developed a self-administered version of the scale and assessed its properties in a pilot study. Methods: The original FAST scale was translated into German via forward and backward translation. Afterwards, we adjusted the scale for self-administered application and inquired participants from two ongoing studies in Germany, 'STAAB' (WĂĽrzburg) and 'BiDirect' (MĂĽnster), both recruiting subjects from the general population across a wide age range (STAAB: 30-79 years, BiDirect: 35-65 years). To assess reliability, agreement of self-assessment with proxy-assessment by partners was measured via intraclass correlation coefficient (ICC) over the FAST score. Construct validity was estimated by conducting correlations with validated scales of depression (PHQ-9), anxiety (GAD-7), and health-related quality of life (SF-12) and regression analyses using these scales besides potentially disabling comorbidities (e.g. Chronic Back Pain (CBP)). Results: Participants (n=54) had a median age of 57.0 years (quartiles: 49.8, 65.3), 46.3% were female. Reliability was moderate: ICC 0.50 (95% CI 0.46-0.54). The FAST score significantly correlated with PHQ-9, GAD-7, and the mental sub-scale of SF-12. In univariable linear regression, all three scales and chronic back pain explained variance of the FAST score. In multivariable analysis, only CBP and the SF-12 remained significant predictors. Conclusion: The German self-administered version of the FAST yielded moderate psychometric properties in this pilot study, indicating its applicability to assess functional impairment in the general population
Quality of life and symptoms among patients with relapsed/refractory AL amyloidosis treated with ixazomib-dexamethasone versus physician's choice
Patient-reported outcomes in AL amyloidosis have not been well-studied. We analyzed health-related quality of life (HRQOL) and AL amyloidosis symptoms data from the phase 3 TOURMALINE-AL1 trial (NCT01659658) (ixazomib-dexamethasone, n = 85; physician's choice of chemotherapy [PC], n = 83). HRQOL and symptom burden were measured with the SF-36v2, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity subscale (FACT/GOG-Ntx), and an amyloidosis symptom questionnaire (ASQ). Score changes during treatment were analyzed descriptively and using repeated-measures linear mixed models; analyses were not adjusted for multiplicity. Least-squares (LS) mean changes from baseline were significantly higher (better HRQOL) for ixazomib-dexamethasone at several cycles for SF-36v2 Role Physical and Vitality subscales (p <.05); no subscales demonstrated significant differences favoring PC. For FACT/GOG-Ntx, small but significant differences in LS mean changes favored ixazomib-dexamethasone over PC at multiple cycles for seven items and both summary scores; significant differences favored PC for one item (trouble hearing) at multiple cycles. ASQ total score trended downward (lower burden) in both arms; significant LS mean differences favored ixazomib-dexamethasone over PC at some cycles (p <.05). Patients with relapsed/refractory AL amyloidosis treated with ixazomib-dexamethasone experienced HRQOL and symptoms that were similar to or trended better than patients treated with PC despite longer duration of therapy
A Survey of Recent Developments in Testability, Safety and Security of RISC-V Processors
With the continued success of the open RISC-V architecture, practical deployment of RISC-V processors necessitates an in-depth consideration of their testability, safety and security aspects. This survey provides an overview of recent developments in this quickly-evolving field. We start with discussing the application of state-of-the-art functional and system-level test solutions to RISC-V processors. Then, we discuss the use of RISC-V processors for safety-related applications; to this end, we outline the essential techniques necessary to obtain safety both in the functional and in the timing domain and review recent processor designs with safety features. Finally, we survey the different aspects of security with respect to RISC-V implementations and discuss the relationship between cryptographic protocols and primitives on the one hand and the RISC-V processor architecture and hardware implementation on the other. We also comment on the role of a RISC-V processor for system security and its resilience against side-channel attacks
A Model-based Sensor Fusion Approach for Force and Shape Estimation in Soft Robotics
International audienceIn this paper, we address the challenge of sensor fusion in Soft Robotics for estimating forces and deformations. In the context of intrinsic sensing, we propose the use of a soft capacitive sensor to find a contact's location, and the use of pneumatic sensing to estimate the force intensity and the deformation. Using a FEM-based numerical approach, we integrate both sensing streams and model two Soft Robotics devices we have conceived. These devices are a Soft Pad and a Soft Finger. We show in an evaluation that external forces on the Soft Pad can be estimated and that the shape of the Soft Finger can be reconstructed
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