A Bayes method for assessing product-reliability during developmenttesting

A fully Bayes approach is presented for analyzing product reliability during the development phase. Based on a Bayes version of the Barlow-Scheuer reliability-growth model, it is assumed that the product goes through a series of test/modification stages, where each product test yields attribute (pass-fail) data, and failure types are classified as fixable or nonfixable. Relevant information on both the failure probabilities and the reliability-growth process is used to motivate the prior joint distribution for the probability of each failure type over the specified range of testing. Results at a particular test-stage can be used to update the knowledge about the probability of each failure type (and thus product reliability) at the current test-stage as well as at subsequent test-stages, and at the end of the development phase. A relative ease of incorporation of prior information and a tractability of the posterior analysis are accomplished by using a Dirichlet distribution as the prior distribution for a transformation of the failure probabilities     

Evolving BlenX programs to simulate the evolution of biological networks

We present a formal approach to study the evolution of biological networks. We use the Beta Workbench and its BlenX language to model and simulate networks in connection with evolutionary algorithms. Mutations are done on the structure of BlenX programs and networks are selected at any generation by using a fitness function. The feasibility of the approach is illustrated with a simple example.     

Response dynamics of phosphorelays suggest their potential utility in cell signalling

Phosphorelays are extended two-component signalling systems found in diverse bacteria, lower eukaryotes and plants. Only few of these systems are characterized, and we still lack a full understanding of their signalling abilities. Here, we aim to achieve a global understanding of phosphorelay signalling and its dynamical properties. We develop a generic model, allowing us to systematically analyse response dynamics under different assumptions. Using this model, we find that the steady-state concentration of phosphorylated protein at the final layer of a phosphorelay is a linearly increasing, but eventually saturating function of the input. In contrast, the intermediate layers can display ultrasensitivity. We find that such ultrasensitivity is a direct result of the phosphorelay biochemistry; shuttling of a single phosphate group from the first to the last layer. The response dynamics of the phosphorelay results in tolerance of cross-talk, especially when it occurs as cross-deactivation. Further, it leads to a high signal-to-noise ratio for the final layer. We find that a relay length of four, which is most commonly observed, acts as a saturating point for these dynamic properties. These findings suggest that phosphorelays could act as a mechanism to reduce noise and effects of cross-talk on the final layer of the relay and enforce its input–response relation to be linear. In addition, our analysis suggests that middle layers of phosphorelays could embed thresholds. We discuss the consequence of these findings in relation to why cells might use phosphorelays along with enzymatic kinase cascades.     

Primary treatment of left coronary artery diseases by percutaneous implantation of stents

Left main coronary artery (LM) stenting has only been reported in bail-out situations or absolute contraindications so surgery. The authors report the immediate and midterm results of primary Palmaz-Schatz stent implantation in two young patients without contraindication to surgery. The first patient, 58 year-old, was admitted for unstable angina in October 1994. Coronary angiography showed an isolated severe ostial lesion of the LM. After conferring with the surgical team which remained on stand-by, angioplasty and stent implantation were performed with excellent results, no complications and no restenosis on angiographic controls at 3 and 12 months. The patient remained asymptomatic 24 months later. The second patient, 38 year-old, was admitted in June 1995 for unstable angina, and coronary angiography showed a severe isolated stenosis in the middle of a long and wide LM. Primary coronary stenting was also performed with excellent results, no complication and no restenosis on angiographic controls at 4 and 8 months. This patient was still asymptomatic 16 months after stenting. These excellent immediate and medium-term results are encouraging and suggest that this form of treatment might be extended to patients with an isolated whether primary LM stent implantation could become a suitable alternative to surgery in the future.     

How to protect hypertrophied myocardium? A prospective clinical trial of three preservation techniques

Protection of the hypertrophied myocardium during heart surgery is still a controversial matter. We prospectively studied 3 currently available preservation techniques in 60 patients operated on for isolated aortic stenosis. Patients were randomly assigned to one of the following groups: CWB: continuous warm blood cardioplegia ICB: intermittent cold blood with warm blood controlled reperfusion Cryst: intermittent cold crystalloid cardioplegia (SLF11, Biosédra Laboratory, Vernon, France). All groups were matched for age, ejection fraction, NYHA class, aortic valve surface, and operative risk score. There were no deaths. No statistically significant difference was found among the groups in terms of ventilatory support time, ICU stay time, hospitalization or atrial fibrillation occurrence. Blood gases in the coronary sinus at the time of clamp release showed deep acidosis with crystalloid cardioplegia (pH = 7.11 vs 7.39 for CWB and 7.38 for UCB, p < 0.0001) associated with a higher lactate production than in the other groups (1.3 mmol vs 0.5 for CWB and 0.58 for ICB, p < 0.0001). Acidosis was corrected at the end of bypass with no significant differences among groups. CK-MB samples were taken on arrival in ICU, then 6 and 24 hours later. These samples showed much higher levels with cold blood (H6: 70 mcg/l vs 33 for CWB and 45 for Cryst, p = 0.0019). Although the 3 types of cardioplegia may be safely used for isolated aortic stenosis surgery, continuous warm blood cardioplegia appears to be the best choice.     

Experimental protocol for mechanical characterization of a femoral implant of carbon-Peek composite hip prosthesis in fatigue

This study concerns the fatigue behavior of a C/Peek hip implant. It is now well-established that the extent of bone loss around a total hip arthroplasty stem is related to stress shielding process. Due to a modulus mismatch between the bone and the implant material, the load transfer to the stem decreases the mechanical stimulus needed by the bone to maintain its structure. Because of its low modulus of elasticity and its good resistance to fatigue in aeronautical applications, the Fiber Carbon/Peek composite could potentially replace some of the metal alloys used in hip stem implant. After a literature survey on biomechanical performances of some fiber carbon composites, including AS4/Peek, experimental quasi-static and fatigue compression tests have been performed on AS4/Peek hip implants. The structural and mechanical characterization of the injection moulded composite material has been realized. The prosthesis compression and fatigue behaviour have been studied with a joint-stimulating apparatus immersed in a physiological solution temperature controlled. Instead of the low specimen homogeneity, no fatigue damage has been revealed either by X-ray observations of stiffness measurements, till ten millions of cycles. The quasi-static compressive fracture morphology has been analyzed by S.E.M. and have shown a good fiber matrix bonding. This mechanical results would suggest that AS4/Peek hip stem are worthy of further investigation as implantable prostheses.     

Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group

PURPOSE: Patients with primary cutaneous melanoma with a Breslow thickness > or = 1.5 mm have only a 30% to 70% probability of survival after surgery, and no adjuvant therapy has so far improved this outcome. Since interferon alfa-2a (IFNalpha2a) exhibits antitumor activity in metastatic melanoma, we investigated whether adjuvant IFNalpha2a diminishes the occurrence of metastases and thus prolongs disease-free survival in melanoma patients after excision of the primary tumor. PATIENTS AND METHODS: In a prospective randomized study, 311 melanoma patients with a Breslow thickness > or = 1.5 mm were assigned to either adjuvant IFNalpha2a treatment (n = 154) or observation (n = 157) after excision of the primary tumor. IFNalpha2a was given daily at a dose of 3 mIU subcutaneously (s.c.) for 3 weeks (induction phase), after which a dose of 3 mIU s.c. three times per week was given over 1 year (maintenance phase). RESULTS: Prolonged disease-free survival was observed in patients treated with IFNalpha2a versus those who underwent surgery alone. This difference was significant (P = .02) for all patients enrolled onto the study (intention-to-treat analysis) at a mean observation time of 41 months. Subgroup analysis showed that Breslow tumor thickness had no influence on treatment results in the groups of patients investigated. CONCLUSION: Adjuvant IFNalpha2a treatment diminishes the occurrence of metastases and thus prolongs disease-free survival in resected primary stage II cutaneous melanoma patients.     

Segmental anatomy of the liver: utility of a nomenclature accepted worldwide

A major use of imaging techniques in the preoperative evaluation of hepatic tumors is to help the surgeon determine the feasibility of hepatic resection. Although the segmental location of tumors is not the sole criterion for determining resectability, such information is crucial for the preoperative planning of the type of resection.     

Effects of freezing temperature and duration of frozen storage on lipid and protein oxidation in chicken meat

This study examined the effects of freezing temperature and duration of frozen storage on lipid and protein oxidation in chicken leg and breast meat. The meat was frozen at three different temperatures (−7, −12 and −18 °C) and then stored at −18 °C for up to 6 months. A significant effect of frozen storage duration on lipid oxidation was detected in leg and breast meat, whereas freezing temperature had no significant effect. In leg meat, freezing at −7 °C had a significant impact on protein oxidation, measured as the increase in carbonyl groups and the decrease in total sulphydryl groups, after 3 months of frozen storage. Lipid and protein oxidation appeared to occur simultaneously in chicken meat during frozen storage and was more intense in leg meat than in breast meat.