A Pattern-based Approach towards Modular Safety Analysis and Argumentation

International audienceSafety standards recommend (if not dictate) performing many analyses during the concept phase of development as well as the early adoption of multiple measures at the architectural design level. In practice, the reuse of architectural measures or safety mechanisms is widely-spread, especially in well-understood domains, as is reusing the corresponding safety-cases aiming to document and prove the fulfillment of the underlying safety goals. Safety-cases in the automotive domain are not well-integrated into architectural models and as such do not provide comprehensible and reproducible argumentation nor any evidence for argument correctness. The reuse is mostly ad-hoc, with loss of knowledge and traceability and lack of consistency or process maturity as well as being the most widely spread and cited drawbacks.Using a simplified description of software functions and their most common error management subtypes (avoidance, detection, handling, ..) we propose to define a pattern library covering known solution algorithms and architectural measures/constraints in a seamless holistic model-based approach with corresponding tool support. The pattern libraries would comprise the requirement the pattern covers and the architecture elements/ measures / constraints required and may include deployment or scheduling strategies as well as the supporting safety case template, which would then be integrated into existing development environments. This paper explores this approach using an illustrative example

Neurologic sequelae of the donor arm after endoscopic versus conventional radial artery harvesting

ObjectiveEndoscopic radial artery harvesting remarkably improves cosmetic results after coronary artery bypass surgery. The aim of this study was to investigate neurologic sequelae of the donor arm compared with those occurring after the conventional harvesting technique.MethodsFifty-three patients who had undergone endoscopic radial artery harvesting were followed up 1 year after the coronary artery bypass operation by means of questionnaire analysis and clinical neurologic investigation (ENDO group). Fifty-three patients who had conventional radial artery harvesting during the same time frame served as control subjects (OPEN group).ResultsPostoperative wound revision was required in 4 patients of the OPEN group (P = .045 vs the ENDO group). Neurologic symptoms of the donor arm were present in 22 (OPEN group) versus 34 (ENDO group) patients (P = .020): a lesion of the superficial radial nerve was shown in 12 (OPEN group) versus 24 (ENDO) patients (P = .014), and a lesion of the lateral antebrachial cutaneous nerve occurred only in the control group in 12 patients (P < .001). Paraesthesia without impaired sensibility was present in 3 (OPEN group) versus 10 (ENDO group) patients (P = .038). Clinical investigation revealed that temperature, pain, and touch sensation, as well as spatial discrimination, were equally impaired in symptomatic patients, whereas vibration sensation was not affected.ConclusionAfter endoscopic radial artery harvesting, impaired sensibility in the region of the superficial radial nerve and paresthesia are more frequent than after the open procedure. However, in contrast to the sequelae of the open procedure, wound revision and injury of the lateral antebrachial cutaneous nerve did not occur. Because of the excellent cosmetic results and avoidance of wound complications, we have opted to use endoscopic radial artery harvesting as the technique of choice, despite the higher incidence of sensory disturbances

Impact of preoperative positron emission tomography in patients with severely impaired LV-function undergoing surgical revascularization

In patients with ischemic cardiomyopathy, coronary artery bypass grafting (CABG) offers an important therapeutic option but is still associated with high perioperative mortality. Although previous studies suggest a benefit from revascularization for patients with defined viability by a non-invasive technique, the role of viability assessment to determine suitability for revascularization in patients with ischemic cardiomyopathy has not yet been defined. This study evaluates the hypothesis that the use of PET imaging in the decision-making process for CABG will improve postoperative patient survival. We reviewed 476 patients with ischemic cardiomyopathy (LV ejection fraction ≤0.35) who were considered candidates for CABG between 1994 and 2004 on the basis of clinical presentation and angiographic data. In a Standard Care Group, 298 patients underwent CABG. In a second PET-assisted management group of 178 patients, 152 patients underwent CABG (PET-CABG) and 26 patients were excluded from CABG because of lack of viability (PET-Alternatives). Primary endpoint was postoperative survival. There were two in hospital deaths in the PET-CABG (1.3%) and 30 (10.1%) in the Standard Care Group (P = 0.018). The survival rate after 1, 5 and 9.3 years was 92.0, 73.3 and 54.2% in the PET-CABG and 88.9, 62.2 and 35.5% in the Standard Care Group, respectively (P = 0.005). Cox-regression analysis revealed a significant influence on long-term survival of patient selection by viability assessment via PET (P = 0.008), of LV-function (P = 0.017), and age >70 (P = 0.016). Preoperative assessment of myocardial viability via PET identifies patients, who will benefit most from CABG

Pulsatile ex vivo perfusion of human saphenous vein grafts under controlled pressure conditions increases MMP-2 expression

<p>Abstract</p> <p>Background</p> <p>The use of human saphenous vein grafts (HSVGs) as a bypass conduit is a standard procedure in the treatment of coronary artery disease while their early occlusion remains a major problem.</p> <p>Methods</p> <p>We have developed an <it>ex vivo </it>perfusion system, which uses standardized and strictly controlled hemodynamic parameters for the pulsatile and non-static perfusion of HSVGs to guarantee a reliable analysis of molecular parameters under different pressure conditions. Cell viability of HSVGs (n = 12) was determined by the metabolic conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) into a purple formazan dye.</p> <p>Results</p> <p>Under physiological flow rates (10 mmHg) HSVGs remained viable for two weeks. Their exposure to arterial conditions (100 mmHg) was possible for one week without important reduction in viability. Baseline expression of matrix metalloproteinase-2 (MMP-2) after venous perfusion (2.2 ± 0.5, n = 5) was strongly up-regulated after exposure to arterial conditions for three days (19.8 ± 4.3) or five days (23.9 ± 6.1, p < 0.05). Zymographic analyses confirmed this increase on the protein level. Our results suggest that expression and activity of MMP-2 are strongly increased after exposure of HSVGs to arterial hemodynamic conditions compared to physiological conditions.</p> <p>Conclusion</p> <p>Therefore, our system might be helpful to more precisely understand the molecular mechanisms leading to an early failure of HSVGs.</p

Atrophy patterns in isolated subscapularis lesions

Background!#!While supraspinatus atrophy can be described according to the system of Zanetti or Thomazeau there is still a lack of characterization of isolated subscapularis muscle atrophy. The aim of this study was to describe patterns of muscle atrophy following repair of isolated subscapularis (SSC) tendon.!##!Methods!#!Forty-nine control shoulder MRI scans, without rotator cuff pathology, atrophy or fatty infiltration, were prospectively evaluated and subscapularis diameters as well as cross sectional areas (complete and upper half) were assessed in a standardized oblique sagittal plane. Calculation of the ratio between the upper half of the cross sectional area (CSA) and the total CSA was performed. Eleven MRI scans of patients with subscapularis atrophy following isolated subscapularis tendon tears were analysed and cross sectional area ratio (upper half /total) determined. To guarantee reliable measurement of the CSA and its ratio, bony landmarks were also defined. All parameters were statistically compared for inter-rater reliability, reproducibility and capacity to quantify subscapularis atrophy.!##!Results!#!The mean age in the control group was 49.7 years (± 15.0). The mean cross sectional area (CSA) was 2367.0 mm!##!Conclusion!#!Analysis of typical atrophy patterns of the subscapularis muscle demonstrates that the CSA ratio represents a reliable and reproducible assessment tool in quantifying subscapularis atrophy. We propose the classification of subscapularis atrophy as Stage I (mild atrophy) in case of reduction of the cross sectional area ratio &amp;lt; 0.4, Stage II (moderate atrophy) in case of &amp;lt; 0.35 and Stage III (severe atrophy) if &amp;lt; 0.3

Myeloid Zinc Finger 1 (Mzf1) Differentially Modulates Murine Cardiogenesis by Interacting with an Nkx2.5 Cardiac Enhancer

Vertebrate heart development is strictly regulated by temporal and spatial expression of growth and transcription factors (TFs). We analyzed nine TFs, selected by in silico analysis of an Nkx2.5 enhancer, for their ability to transactivate the respective enhancer element that drives, specifically, expression of genes in cardiac progenitor cells (CPCs). Mzf1 showed significant activity in reporter assays and bound directly to the Nkx2.5 cardiac enhancer (Nkx2.5 CE) during murine ES cell differentiation. While Mzf1 is established as a hematopoietic TF, its ability to regulate cardiogenesis is completely unknown. Mzf1 expression was significantly enriched in CPCs from in vitro differentiated ES cells and in mouse embryonic hearts. To examine the effect of Mzf1 overexpression on CPC formation, we generated a double transgenic, inducible, tetOMzf1-Nkx2.5 CE eGFP ES line. During in vitro differentiation an early and continuous Mzf1 overexpression inhibited CPC formation and cardiac gene expression. A late Mzf1 overexpression, coincident with a second physiological peak of Mzf1 expression, resulted in enhanced cardiogenesis. These findings implicate a novel, temporal-specific role of Mzf1 in embryonic heart development. Thereby we add another piece of puzzle in understanding the complex mechanisms of vertebrate cardiac development and progenitor cell differentiation. Consequently, this knowledge will be of critical importance to guide efficient cardiac regenerative strategies and to gain further insights into the molecular basis of congenital heart malformations

Development of a GEM-TPC prototype

The use of GEM foils for the amplification stage of a TPC instead of a con- ventional MWPC allows one to bypass the necessity of gating, as the backdrift is suppressed thanks to the asymmetric field configuration. This way, a novel continuously running TPC, which represents one option for the PANDA central tracker, can be realized. A medium sized prototype with a diameter of 300 mm and a length of 600 mm will be tested inside the FOPI spectrometer at GSI using a carbon or lithium beam at intermediate energies (E = 1-3AGeV). This detector test under realistic experimental conditions should allow us to verify the spatial resolution for single tracks and the reconstruction capability for displaced vertexes. A series of physics measurement implying pion beams is scheduled with the FOPI spectrometer together with the GEM-TPC as well.Comment: 5 pages, 4 figures, Proceedings for 11th ICATTP conference in como (italy

Seasonal hydrology drives rapid shifts in the flux and composition of dissolved and particulate organic carbon and major and trace ions in the Fraser River, Canada

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Biogeosciences 12 (2015): 5597-5618, doi:10.5194/bg-12-5597-2015.Rapid changes in the volume and sources of discharge during the spring freshet lead to pronounced variations in biogeochemical properties in snowmelt-dominated river basins. We used daily sampling during the onset of the freshet in the Fraser River (southwestern Canada) in 2013 to identify rapid changes in the flux and composition of dissolved material, with a focus on dissolved organic matter (DOM). Previous time series sampling (at twice monthly frequency) of dissolved inorganic species in the Fraser River has revealed smooth seasonal transitions in concentrations of major ions and tracers of water and dissolved load sources between freshet and base flow periods. In contrast, daily sampling reveals a significant increase in dissolved organic carbon (DOC) concentration (200 to 550 μmol L−1) occurring over a matter of days, accompanied by a shift in DOM optical properties, indicating a transition towards higher molecular weight, more aromatic DOM composition. Comparable changes in DOM composition, but not concentration, occur at other times of year, underscoring the role of seasonal climatology in DOM cycling. A smaller data set of total and dissolved Hg concentrations also showed variability during the spring freshet period, although dissolved Hg dynamics appear to be driven by factors beyond DOM as characterized here. The time series records of DOC and particulate organic carbon (POC) concentrations indicate that the Fraser River exports 0.25–0.35 % of its annual basin net primary productivity. The snowmelt-dominated hydrology, forested land cover, and minimal reservoir impoundment of the Fraser River may influence the DOC yield of the basin, which is high relative to the nearby Columbia River and of similar magnitude to that of the Yukon River to the north. Anticipated warming and decreased snowfall due to climate changes in the region may cause an overall decrease in DOM flux from the Fraser River to the coastal ocean in coming decadesThis work was partially supported by a WHOI Ocean Ventures Fund award to BMV and NSF grants EAR-1226818 to BPE, OCE-0851015 to TIE, BPE, and VG, and OCE-0851101 to RGMS, and support to BPE from Jane and James Orr

Tracing river chemistry in space and time : dissolved inorganic constituents of the Fraser River, Canada

Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 124 (2014): 283-308, doi:10.1016/j.gca.2013.09.006.The Fraser River basin in southwestern Canada bears unique geologic and climatic features which make it an ideal setting for investigating the origins, transformations and delivery to the coast of dissolved riverine loads under relatively pristine conditions. We present results from sampling campaigns over three years which demonstrate the lithologic and hydrologic controls on fluxes and isotope compositions of major dissolved inorganic runoff constituents (dissolved nutrients, major and trace elements, 87Sr/86Sr, δD). A time series record near the Fraser mouth allows us to generate new estimates of discharge-weighted concentrations and fluxes, and an overall chemical weathering rate of 32 t km-2 y-1. The seasonal variations in dissolved inorganic species are driven by changes in hydrology, which vary in timing across the basin. The time series record of dissolved 87Sr/86Sr is of particular interest, as a consistent shift between higher (“more radiogenic”) values during spring and summer and less radiogenic values in fall and winter demonstrates the seasonal variability in source contributions throughout the basin. This seasonal shift is also quite large (0.709 – 0.714), with a discharge-weighted annual average of 0.7120 (2 s.d. = 0.0003). We present a mixing model which predicts the seasonal evolution of dissolved 87Sr/86Sr based on tributary compositions and water discharge. This model highlights the importance of chemical weathering fluxes from the old sedimentary bedrock of headwater drainage regions, despite their relatively small contribution to the total water flux.This work was supported by the WHOI Academic Programs Office and MIT PAOC Houghton Fund to BMV, a WHOI Arctic Research Initiative grant to ZAW, NSF-ETBC grant OCE-0851015 to BPE and TIE, and NSF grant EAR-1226818 to BPE