Variation management by functional tolerance allocation and manufacturing process selection

The imperfections of the manufacturing process lead to functional characteristics degradation, and therefore product quality. To ensure a certain level of product quality, the synthesis of tolerance (tolerance design) aims to determine the acceptable limits of the characteristics of parts, assemblies... The allocation or synthesis of functional tolerances is an important step in the design process which takes place generally during the detailed design and greatly impacts the design of the manufacturing process, manufacturing and product control. That is why it is important, when functional tolerances are quantified, to take into account their impacts on the manufacturing cost and product quality. These two concepts (manufacturing cost and product quality) are usually considered as conflicting goals. The proposed approach aims to allocate the functional tolerances that provide the best ratio between functional performances and manufacturing cost. It is based on the “Key Characteristics” approach, developed by Boeing coupled with an activities approach. This optimization is carried out by a genetic algorithm. The process selection is performed by a constraint satisfaction algorithm. Finally, the impacts of process choices are assessed with the Monte Carlo simulation which calculates the behavior and quality of the resulting product.     

Expression and regulation of intercellular adhesion molecule-1 (ICAM-1) in organotypic cultures of rat liver tissue

Background/Aims: The objective of the present study was to analyze the expression and regulation of intercellular adhesion molecule-1 (ICAM-1) in organotypic cultures of rat liver slices, which preserve the normal microenvironment of liver cells.Methods: Rat liver slices were maintained in culture for 15 min to 24 h and examnied for ICAM-1 expression by immunohistochemistry and Western blotting in basal conditions and after stimulation with 1000 IU/ml interferon-γ (IFNγ), 1000 IU/ml tumor necrosis factor-α (TNFα) and 50 μg/ml endotoxin. Immunohistochemical results were evaluated using a semiquantitative scoring system.Results: In uncultured slices, ICAM-1 was not detected on hepatocytes. In unstimulated liver slices maintained in organotypic culture, ICAM-1 was induced at the surface of scattered hepatocytes (score at 15 min, 0.33±0.47 and at 24 h, 1.17±0.69). After 4 h of stimulation, a significant increase in ICAM-1 expression by hepatocytes and adjacent sinusoidal cells, but not by intra-hepatic biliary epithelial cells, was observed for IFNγ (score: 2.35±0.47) and endotoxin (score: 2.67±0.47), but not with TNFα (score: 0.66±0.47). After 24 h of stimulation, a further increase in the extent of ICAM-1 expression by hepatocytes was observed for IFNγ (score: 3.67±0.47) and endotoxin (score: 4.0±0.0), and a significant overexpression of ICAM-1 by hepatocytes was detectable after treatement with TNFα (score: 3.67±0.47).Conclusions: In rat liver organotypic cultures, TNFα, IFNγ and endotoxin induce the expression of ICAM-1 in hepatocytes and adjacent sinusoidal endothelial cells, but not in portal tracts.     

Comparison of transthoracic echocardiography using second harmonic imaging, transcranial Doppler and transesophageal echocardiography for the detection of patent foramen ovale in stroke patients.

AIMS: The comparison of three imaging methods to determine which is the most accurate and reliable for the detection of right-to-left shunt. METHODS AND RESULTS: One hundred and seven patients who were hospitalized for stroke underwent: a transthoracic echocardiography (TTE) using second harmonic, a transcranial Doppler (TCD) and a transesophageal echocardiography (TEE) from August 2003 to April 2004. All studies were recorded on a videotape and were studied by a physician blinded to the study. With TTE and TEE, we found 44 (41%) patent foramen ovales. All contrast tests were positive with TCD for these 44 patients. For two patients, the contrast test was positive only with TTE and TCD. We found four false negative contrast tests with TTE. Among the 63 patients who had a negative contrast test with TEE and TTE, the results were the same with TCD for 59 of them; we were not able to determine a cause for the four positive tests. CONCLUSION: This study confirms that transesophageal echocardiography has limitations in the diagnosis of patent foramen ovale. In this study, the negative predictive value of transcranial Doppler was excellent. Therefore, this examination is able to exclude a patent foramen ovale with a high level of confidence.     

Better results with rhenium-186 radiosynoviorthesis than with cortivazol in rheumatoid arthritis (RA): a two-year follow-up randomized controlled multicentre study

OBJECTIVE: The aim of this international multicentric randomized phase 3 clinical trial was to compare prospectively radiosynoviorthesis (RSO) with rhenium-186-sulfide (186Re) to intra-articular corticotherapy in patients with clinically controlled rheumatoid arthritis (RA), but in whom one or a few medium-sized joints remained painful or swollen. METHODS: One hundred and twenty-nine joints in 81 RA patients [stratified into 2 groups: wrists (group 1, n = 78) and all the other joints (group 2, n = 51, including 18 elbows, 21 shoulders and 12 ankles)] were randomized to receive intra-articular injections of either 186Re-sulfide (64 +/- 4 MBq), or cortivazol (Altim) 3.75 mg. Clinical assessment was performed before and then at 3, 6, 12, 18 and 24 months after local therapy, using a 4-step verbal rating scale (VRS) and a 100 mm visual analog scale for pain, a 4-step VRS for joint swelling and mobility and a 2-step VRS for the radiological stage. The Mantel-Haenszel test was used for qualitative variables, analysis of variance (ANOVA) for quantitative pain analysis and Kaplan-Meyer survival test for relapse analysis. RESULTS: 186Re was observed to be statistically superior to cortivazol at 18 and 24 months while no statistical difference was seen for any criterion at 3, 6 and 12 months post injection. At 24 months, the difference in favor of 186Re was significant for pain (p = 0.024), joint swelling (p = 0.01), mobility (p = 0.05, non-wrists only), pain and swelling (p = 0.03) and pain or swelling (p = 0.02). "Survival" studies (Kaplan-Meyer) demonstrated a greater relative risk of relapse in corticoid treated joints, but only from the second year of follow-up. No serious side effect was observed in any patient, with only light and transient local pain and/or swelling occurring in 24% of cases, regardless of the treatment used. CONCLUSION: 186Re-sulfide and cortivazol had similar efficacy up to 12 months post-injection, but 186Re became clearly more effective at 18 and 24 months, for all criteria monitored and for RA outcome. Therefore, 186Re RSO can be recommended for routine clinical use.     

Effects of vitamin D in the elderly population: current status and perspectives

Besides its well-known effect on bone metabolism, recent researches suggest that vitamin D may also play a role in the muscular, immune, endocrine, and central nervous systems. Double-blind RCTs support vitamin D supplementation at a dose of 800 IU per day for the prevention of falls and fractures in the senior population. Ecological, case–control and cohort studies have suggested that high vitamin D levels were associated with a reduced risk of autoimmune diseases, type 2 diabetes, cardio-vascular diseases and cancer but large clinical trials are lacking today to provide solid evidence of a vitamin D benefit beyond bone health. At last, the optimal dose, route of administration, dosing interval and duration of vitamin D supplementation at a specific target dose beyond the prevention of vitamin D deficiency need to be further investigated.     

Two cases of acute leukemia following treatment of malignant glioma

Two female patients, 42 and 30 years old, respectively, died of acute nonlymphocytic leukemia 43 and 38 months, respectively, after a subsequent treatment: chemotherapy for one and irradiation and chemotherapy for the other, following excision of a malignant glioma. At the time of death, both seemed to be in complete remission of their brain tumor. Both had been treated with procarbazine and nitrosoureas. The latter were responsible for severe myelosuppressive episodes and seem to have played an essential role in the induction of the leukemia. In one case, a myelodysplasia was observed before the onset of the AL and the diagnosis of refractory anemia with excess of blasts seemed warranted. Secondary acute leukemias are rare in the evolution of malignant gliomas and the usefulness of subsequent radiochemotherapy cannot be questioned at the present time. The risks involved in this therapy are minor when compared to the short-term fatal prognosis of this type of tumor. Cancer 52:222-226, 1983.