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The α- and β-polymorphs of Cd[Pt(CN)4] are densely packed 3-D coordination polymers with quantum yields of 0.85 and 0.79. They react with donor solvent vapours to give emissive 2-D CdL2[Pt(CN)4] (L = DMSO, DMF, pyridine) cyanometallate sheets.

Luminescence spectra measured at variable pressure can reveal unique insight on ground- and emitting state properties of transition metal compounds. This chapter summarizes illustrative results for chromium(III) complexes with the d3 electron configuration and oxo complexes of rhenium(V) and molybdenum(IV) with the d2 configuration. Their luminescence transitions only involve electronic configuration changes within the t2 (O point group) molecular orbitals, leading to narrow spin-flip bands and broad bands with vibronic structure for the chromium(III) and metal-oxo complexes, respectively.

Silver protected is one of the most required coating for space observation telescopes covering the wavelength range from 430 nm to infra-red. Many challenges have to be addressed in such coatings including high efficiency over the wide spectrum, high durability with behavior in AIT conditions and during flight. Thales SESO has already produced more than 166 total space mirrors from which 87 are flying successfully since many years. Most of them are coated with protected silver coatings. For over the past 20 years, Thales SESO has enhanced the characteristics of our coating related to its durability in acceptance test conditions, its mechanical stability when going to vacuum and its behavior toward space aggressions such as ATOX or radiations. A lot of the corresponding developments were substantially sustained by CNES, together with Thales Alenia Space through different French programs. Previous realizations include Pleiades, French national program, MTG mirrors both for sounders (IRS instrument) and imagers (FCI instrument), Sentinel 3 with Na and Ob mirrors and different other export programs. The last improvements were made in the frame of TANGO program for Thales Alenia Space/CNES, with improved adhesion during acceptance tests, with ability to apply the full coating process on sub-assemblies including glued parts, and with reduction in the stress induced on the substrate. The performance and uniformity were demonstrated on 1700 mm diameter in Thales SESO STEP large coating chamber. Through these different developments Thales SESO has gained maturity in the contribution of the coating on stress induced in the mirror as well as its stability when going to vacuum. We now perfectly anticipate this effect in the polishing process. Here after, you find an overview of the Thales SESO realizations starting from Pleiades first results to the status achieved with the last improvements on TANGO program and future prospective developments.

Thales Alenia Space is designing and developing space observation instruments since more than 40 years. This paper explains why active optics is needed for next generation of instruments for Earth observation. It describes what kind of solution is preferred and gives an overview of the development status on the associated technologies. Indeed, the future missions will have to deal with better performance, better optical quality while from manufacturing point of view, the total mass, the development schedule and the final cost have to be reduced. These constraints induce a new generation of solutions based on large entrance optics associated to high lightweight ratio which naturally provide solutions sensitive to gravity deformation. In these conditions, the enhancement of the final performance can only be guaranteed by using active optics in flight. A deformable mirror is therefore foreseen to be implemented in future large telescopes in order to correct manufacturing residues and ground/flight evolution, including gravity. Moreover, low mass and low cost require more compact designs which entail solutions more sensitive to misalignment. An active positioning mechanism is then also needed in order to correct the telescope alignment during operation conditions. Thales Alenia Space has been selected by CNES to develop and qualify active optics building blocks and then to test and demonstrate the improvement that new active technologies can bring in a full size instrument representative of the next generation of observation instruments. An overview of the current development status and the achieved performances is given for each building block (Primary Mirror, deformable mirror, 6-dof mechanism, wavefront sensor).

Thales Alenia Space has been involved in the design and the development of space observation instruments for over 40 years. This paper will explain why active optics is needed for next generation of instruments for Earth observation. We will also describe what kind of solution is preferred and why. We will give an overview of the development status on the associated technologies. Indeed, the future missions will have to deal with better performance, better optical quality while from manufacturing point of view, the total mass, the development schedule and the final cost have to be reduced. These constraints induce a new generation of solutions based on large entrance optics associated to high lightweight ratio which naturally provide solutions sensitive to gravity deformation. In these conditions, the enhancement of the final performance can only be guaranteed by using active optics in flight. A deformable mirror is therefore foreseen to be implemented in future large telescopes in order to correct manufacturing residues, ground/flight evolution including gravity. Moreover, low mass and low cost require more compact designs which entail solutions more sensitive to misalignment. An active positioning mechanism is then also needed in order to correct the telescope alignment during operation conditions. Thales Alenia Space has been selected by CNES to develop and qualify active optics building blocks and then to test and demonstrate the improvement that new active technologies can bring in a full size instrument representative of the next generation of observation instruments. An overview of the current development status and the achievable performances is given.

Background: Continuing to smoke or to drink after the treatment of an upper aerodigestive tract (UADT) cancer is known to worsen the prognosis. We assessed the feasibility and efficacy of an addiction treatment program integrated into the cancer treatment. Method: In four units devoted to UADT tumors, we proposed an addiction treatment to all patients still drinking or smoking at the end of the cancer treatment; the abstinence rate was assessed 6 and 12 months later. Results: One hundred and sixteen patients were included. Among the 73 patients still drinking and/or smoking at the end of the cancer treatment, 46.6% accepted an addiction treatment. In the latter, abstinence rate was increased, 52.2% versus 31.03% ( p = .07) at M12. In patients both drinking and smoking, addiction treatment doubled the rate of abstinence of both products (31% vs. 14%). Conclusion: Offering addiction treatment to patients with UADT cancer improves abstinence rate and helps maintain long-term withdrawal.

International audience; BACKGROUND: The standard-of-care treatment of patients with hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis includes pegylated interferon α (PegIFN)-α plus ribavirin and/or rituximab. About 30-40% of patients are non-responders or relapsers to such combination. OBJECTIVE: To analyse the safety and efficacy of Peg-IFNα/ribavirin/protease inhibitor combination in HCV-MC vasculitis. PATIENTS AND METHODS: Open-label, prospective, cohort study including 23 patients with HCV-MC vasculitis. Peg-IFNα/ribavirin was associated to telaprevir (375 mg three times daily, for 12 weeks, (n=15)) or boceprevir (800 mg three times daily, for 44 weeks, (n=8)) for 48 weeks. RESULTS: The median age was 59 (52.5-66) years, with 48.8% women. Thirteen patients (56.5%) were complete clinical responders, and 10 (43.5%) were partial responders at week 24. The virological response (ie, HCV RNA negativation) was of 69.6% at week 24 (p=0.005). The cryoglobulin level decreased from 0.44 to 0.06 g/l (p=0.0006) and the C4 level increased from 0.09 to 0.15 g/l (p=0.045). Grades 3 and 4 adverse events (mainly anaemia, neutropenia and thrombocytopenia) were observed in 10 cases (43.5%). Twenty patients (87%) received erythropoietin, 9 (39.1%) had red cell transfusion, and 2 (8.7%) had granulocyte stimulating agents. Antiviral therapy discontinuation was required in 8 (34.7%) patients for virological non-response (n=5), virological relapse (n=2) and depression (n=1). CONCLUSIONS: Peg-IFNα/ribavirin/protease inhibitor combination seems highly effective in HCV-MC. Such therapeutic regimen should be administered cautiously considering the high rate of side effects.

Background: Ultrasonography (US) is the best diagnostic tool in the initial assessment of thyroid nodule. Giving its appropriateness and accessibility, ultrasound-based thyroid imaging reporting and data systems (TIRADS) classifications have been developed with main goal to standardize reporting and facilitate communication between practitioners, and to indicate when fine-needle aspiration biopsy (FNAB) should be performed. Objective: To determine the reliability of Russ’ modified TIRADS classification in predicting thyroid malignancy. Materials and Methods: It was a cross sectional study carried out at Centre Hospitalier de Lagny, Marne La Vallee (France). Consecutive records of patients with focal thyroid nodules on ultrasound (US) for which US-guided FNAB was performed and pathology results were available, from January 2007 to August 2012, were selected for review. The risk of malignancy of each TIRADS category was determined and correlation with pathology assessed. Statistical performances of some US features were also assessed. The threshold for statistical significance was set at 0.05. Results: A total of 430 records of patients were eligible. Twenty-three out of 430 (5.3%) nodules were malignant. The risk of malignancy of the TIRADS categories were as follows: TIRADS2 0%, TIRADS3 2.2%, TIRADS4A 5.9%, TIRADS4B 57.9%, TIRADS5 100% (Gamma statistic = 0.85; Spearman correlation = 0.30, Pearson’s R = 0.37, p < 0.001). Some US features were associated with a higher risk of malignancy: irregular contours (OR = 22.4), taller-than-wide shape (OR = 19.5), microcalcifications (OR = 15.2), and marked hypoechogenicity (OR = 12.7). Conclusion: Russ’ modified TIRADS classification is reliable in predicting thyroid malignancy. More evidence is nevertheless necessary for widespread adoption and use.

Assessing variation in breeding performance in relation to habitat characteristics may provide insights into predicting the consequences of land-use change on species ecology and population dynamics. We compared four Marsh Harrier Circus aeruginosus populations subject to similar environmental conditions, but which differed in habitat composition, ranging from natural habitats to intensively cultivated areas. Using a 6-year dataset, we characterized breeding habitat and diet in these four study sites, and analysed breeding performance in relation to this gradient of land-use intensification. There was minimal variation in breeding performance between study years but consistent variation between study sites. Unexpectedly, Marsh Harriers breeding in intensively cultivated habitats had higher reproductive success than those breeding in more natural habitats, which, however, hosted higher breeding densities, so overall net population productivity (fledglings per unit area) was similar across sites. This resulted from combined effects of density-dependence and different predation rates between study sites. The colonization of intensive farmland habitats may not necessarily impact negatively on population sustainability when breeding success and population density are traded against each other. However, our findings should not mask longer-term conservation issues for populations breeding in these intensively managed areas, and further studies should assess potential long-term negative effects of occupancy of human-altered habitat.

Hereditary fibrinogen A -chain amyloidosis: Phenotypic characterization of a systemic disease and the role of liver transplantation. Blood 115: 2998–3007, 2010 Arie J. Stangou, Nicholas R. Banner, Bruce M. Hendry, Mohamed Rela, Bernard Portmann, Julia Wendon, Mark Monaghan, Philip MacCarthy, Muriel Buxton-Thomas, Christopher J. Mathias, Juris J. Liepnieks, John O’Grady, Nigel D. Heaton, and Merrill D. Benson Fibrinogen amyloidosis due to mutations in the fibrinogen -chain gene (AFib) localized on chromosome 4 and composed of six exons belongs to the group of nonneuropathic hereditary renal amyloidoses. It is the most common type of all hereditary renal amyloid diseases in the United States and Europe. Like other forms of amyloidosis, AFib amyloidosis is a protein misfolding disorder. Fibrinogen production is exclusively hepatic. Liver transplantation was therefore considered as a logical mode of treatment, whereas isolated renal transplantation was followed by kidney amyloid recurrence in most patients. Stangou et al. have first revisited the current phenotypic description of AFib amyloidosis and second performed a systematic evaluation for liver and kidney transplantation (LKT) in a series of 22 patients (8 women, 14 men). Three of them had been misdiagnosed as primary systemic AL amyloidosis—a diagnostic error already reported (1). The median age at presentation was 55 years (range 33 to 63 years). Proteinuria was the most common presenting feature (median 24-hour urine protein 7.2 g; range 0 to 11.8 g). At the time of assessment, median GFR was 16 ml/min (range 0 to 52 ml/min). Renal biopsy was performed in 21 of 22 patients and revealed amyloidosis in all patients, with enlarged glomeruli replaced by amyloid with minimal or no extraglomerular involvement—a finding suggestive of this type of amyloidosis (1). Twenty of 22 patients progressed to ESRD. Two patients had liver amyloidosis, complicated in one by end-stage liver disease. Coronary atherosclerotic disease was documented in 15 patients (68%), in half of the patients predating evolution of kidney impairment. Twelve patients had severe systemic vascular disease, involving aorta, splanchnic, or carotid arteries. Two patients underwent carotid endarterectomy. Of interest, the excised material contained amyloid purely consistent of mutant fibrinogen A -chain. Cardiac amyloidosis was not a rare localization. Echocardiography was abnormal in 11 of 21 patients (52%). Three of the four endomyocardial biopsies revealed substantial amyloid deposition. One patient developed dilated amyloid cardiomyopathy in association with coronary disease and myocardial amyloidosis, whereas cardiac amyloidosis usually leads to restrictive cardiomyopathy. In addition, cardiac parasympathetic dysfunction and risk of bradycardia were identified in 12 patients. Seven of them had pacemaker insertion. Autonomic involvement of the gastrointestinal tract was a feature in 15 patients. Only 24% of patients had family history of renal disease. However, 81% had family history of systemic or coronary vascular disease. Family members who had such cardiovascular history were indeed carriers of AFib mutations. Spontaneous splenic rupture occurred in four patients (one during hemodialysis and three during transplantation). The excised spleen contained widespread amyloid. Nine of 14 patients accepted on the waiting list received combined liver and kidney allografts. At a median follow-up of 67 months, six of nine patients are alive and well with normal liver function. Five patients have good renal function. Cardiac amyloidosis has not progressed after LKT. I-labeled serum amyloid P component (SAP) scintigraphy showed regression of systemic visceral amyloid deposits as early as at the first annual follow-up scan after LKT, whereas scintigraphy documented progressive amyloid deposition in two patients who had previously undergone isolated kidney transplant. Serial 99mTcDMSA renal scintigraphy after preemptive LKT in two patients demonstrated stable native renal uptake. Four patients with various liver diseases received, after full information, explanted livers from AFib patients. Only one “domino” recipient had SAP scans and echocardiography for up to 5 years with no evidence of de novo amyloid deposition. The study by Stangou et al. extends the clinical scope of AFib amyloidosis. Stangou et al. encourage evaluation of isolated liver transplant early in the course of amyloid nephropathy to prevent systemic deposition and renal progression to ESRD. Amyloid fibrils in AFib contain exclusively variant fibrinogen. Circulating total fibrinogen consists of a mixture of wild-type/ variant fibrinogen in a ratio of 1:1 to 3:2. Wild-type fibrinogen does not perpetuate amyloid disease. After liver transplant, the variant fibrinogen is eliminated and promptly replaced by Published online ahead of print. Publication date available at www.cjasn.org.

Treatment of hepatitis C (HCV)–mixed cryoglobulinemia (MC) may target either the viral trigger (HCV) or the downstream B-cell clonal expansion. Prospective cohort study of 38 HCV-MC patients who received a combination of rituximab (375 mg/m2) once a week for 1 month followed by Peg-interferon-α (Peg-IFN-α; 2a, 180 μg or 2b, 1.5 μg/kg) weekly plus ribavirin (600-1200 mg) daily for 48 weeks were compared with 55 HCV-MC patients treated by Peg-IFN-α/ribavirin with the same modalities. In the whole population of HCV-MC patients (n = 93), a complete clinical response was achieved in 73.1% (68 of 93), cryoglobulin clearance in 52.7% (49 of 93), and a sustained virologic response in 59.1% (55 of 93). Compared with Peg-IFN-α/ribavirin, rituximab plus Peg-IFN-α/ribavirin–treated patients had a shorter time to clinical remission (5.4 ± 4 vs 8.4 ± 4.7 months, P = .004), better renal response rates (80.9% vs 40% of complete response, P = .040), and higher rates of cryoglobulin clearance (68.4% vs 43.6%, P = .001) and clonal VH1-69+ B-cell suppression (P < .01). Treatment was well tolerated with 11% of discontinuation resulting from antiviral therapy and no worsening of HCV RNA under rituximab. Our findings indicate that rituximab combined with Peg-IFN-α/ribavirin is well tolerated and more effective than Peg-IFN-α/ribavirin in HCV-MC.

The scaling of a family of five baroque recorders is studied considering two aspects: the compass of each instrument and the control parameters. The observations are interpreted in terms of the homogeneity of the timbre. The control parameters are measured on an experienced player performing a simple scale task on each of the instruments, and are described in the frame of the hydrodynamic jet behaviour. On the family studied, the geometrical parameters appear to be adjusted so that the control parameters are similar on all the instruments. Low-pitched instruments present an enrichment of their spectra in high frequencies.

Background Despite great progress in understanding the mechanisms underlying genetic hemochromatosis, data on the prevalence and the penetrance of the disorder are conflicting.Design and Methods A registry of patients with genetic hemochromatosis was established in the South of France and a regional health network was developed to allow the inclusion of all the diagnosed patients. C282Y homozygous patients classified in stages 2 (biological iron overload), 3 and 4 (clinical manifestations of iron overload, stage 4 being the more severe) according to the classification of the French National Authority for Health were included in the registry over a 6-year period.Results A total of 352 symptomatic C282Y homozygotes were identified, resulting in a total prevalence of 1.83 per 10,000 (95% CI: 1.63 to 2.02) in subjects over 20 years and 2.40 per 10,000 (95% CI, 2.15 to 2.65) among subjects of European descent. Among Europeans, the total calculated penetrance was 15.8% in stage 2 or higher, 12.1% in stage 3 or 4 and 2.9% in stage 4. The penetrance was slightly higher in males (18.7%) than in females (13.2%). It was 19.9% for individuals over 40 years of age (24.1% and 16.3% in males and females, respectively) with a maximum of 31% in subjects between 50 and 54 years old. Among 249 patients with complete records, 24% were in stage 2, the majority (58%) were in stage 3, and 18% in stage 4. There was a higher proportion of males, and excessive alcohol intake was more prevalent in stage 4 than in stages 2 and 3 combined.Conclusions A French Mediterranean regional hemochromatosis registry with strict inclusion criteria is a useful tool for characterizing the history of this disease, particularly for the most severely affected patients, as defined by the disease severity classification. The total prevalence of symptomatic C282Y homozygotes in the region was found to be low. However, clinical penetrance (stages 3 and 4) was not negligible.

Objective To report on the long-term followup of a cohort of patients with hepatitis C virus (HCV)–related vasculitis treated with rituximab with or without PEGylated interferon alfa-2b (PEG–IFN alfa-2b) plus ribavirin. Methods The study group comprised 32 HCV RNA–positive patients with HCV-related vasculitis: 20 patients were treated with rituximab and PEG–IFN alfa-2b (9 of whom had not previously received antiviral treatment and 11 of whom had experienced disease resistance to or relapse with antiviral treatment), and 12 antiviral-intolerant patients were treated with rituximab alone. Results Treatment with rituximab and PEG–IFN alfa-2b plus ribavirin induced a complete clinical response and a partial clinical response in 80% and 15% of patients, respectively, a complete immunologic response and a partial immunologic response in 67% and 33% of patients, respectively, and a sustained virologic response in 55% of patients. Treatment with rituximab alone induced a complete clinical response and a partial clinical response in 58% and 9% of patients, respectively, and a complete immunologic response and a partial immunologic response in 46% and 36% of patients, respectively. B cell depletion was achieved in 96% of patients, and B cell recovery began after a median delay of 12 months. After a mean ± SD followup period of 23 ± 12 months, 22% of patients experienced a clinical relapse, and 34% of patients experienced an immunologic relapse. All relapses were associated with the absence of virologic control, and 78% of relapses were associated with B cell recovery. Six patients were re-treated with rituximab. All 6 of these patients had a complete clinical response, 50% had a complete immunologic response, and 50% had a partial immunologic response. Rituximab was well tolerated overall. Conclusion Rituximab is an effective treatment of severe and/or refractory HCV-related vasculitis. Relapses were consistently associated with the absence of virologic control. The clinical and immunologic efficacy of rituximab after repeated infusion appeared to be the same as that observed after induction therapy.

Le marketing industriel a longtemps ignore le cas de la sous-traitance. Il semblerait que les operateurs n’aient guere de possibilites de mettre en œuvre une activite marketing et de la maitriser. Or, une approche en termes de reseau permet de creer une nouvelle dynamique.Favorable au sous-traitant. Devenu pro-actif, il fonde desormais sa competitivite sur un nouveau metier d’assemblage de competences, precisement a dominante marketing.

Background: New genetic forms of hereditary hemochromatosis (HH) or hereditary hyperferritinemia (HF) have been identified over the last few years, and abnormalities of various genes may interact in a single patient. This study aimed to develop a rapid automated method for sequencing the main genes involved. Methods: We used a standard 96-well microplate with a single PCR condition in an adaptation of the SCAIP (single-condition amplification with internal primer) method to sequence the HFE (hemochromatosis), HAMP (hepcidin antimicrobial peptide), HFE2/HJV [hemochromatosis type 2 (juvenile)], SLC40A1 (ferroportin), and TFR2 (transferrin receptor 2) genes, and the 5′ untranslated region of the FTL (ferritin, light polypeptide) gene. To further simplify the method, we adjusted PCR conditions to avoid the use of an internal primer and applied this single-condition amplification method to 38 selected, unrelated patients. We tailored the genetic investigation according to the clinical picture, with the patients falling into 2 groups. Group 1 consisted of patients with hyperferritinemia and high transferrin saturation (TS) (classic adult and juvenile HH forms, groups 1A and 1B, respectively), and group 2 consisted of patients with hyperferritinemia and low, typical, or slightly increased TS, with or without iron overload (groups 2A and 2B, respectively). Results: With this strategy we identified single-gene and multigene abnormalities, including 6 previously undescribed abnormalities in HFE (c.794dupA), HFE2 (c.–89–4dupT), and SLC40A1 (c.262A>G, c.533G>A, c.1468G>A, and c.–59_–45del). Conclusion: This method is a simple approach for investigating hereditary iron overload or HF and allows rapid evaluation of patients.

The aim of this study was to analyse the safety and efficacy of the PegIFNα/ribavirin/protease inhibitor combination in severe and/or refractory hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis.This prospective cohort study included 30 patients (median age 59 years [53-66] and 57% of women) with HCV-MC vasculitis. PegIFNα/ribavirin (for 48 weeks) was associated with telaprevir (375 mg three times daily, for 12 weeks, [n = 17]) or boceprevir (800 mg three times daily, for 44 weeks, (n = 13]).Twenty three patients (76.7%) were non-responders to previous antiviral therapy. At week 72, twenty patients (66.7%) were complete clinical and sustained virological responders. The cryoglobulin level decreased from 0.45 to 0 g/L (p0.0001) and the C4 level increased from 0.09 to 0.14 g/L (p = 0.017). Complete clinical responders had a higher frequency of purpura (16/20 [80%] vs. 4/10 [40%], p = 0.045), and a trend towards lower frequency of neuropathy (9/20 (45%) vs. 8/10 [80%], p = 0.12) compared with partial responders. Serious adverse events occurred in 14 patients (46.6%) during the 72 weeks of follow-up. Twenty eight patients (93.3%) received erythropoietin, 14 (46.6%) had red blood cell transfusion and 2 (6.6%) received granulocyte stimulating agent. The baseline factors associated with serious adverse events included liver fibrosis (p = 0.045) and a low platelet count (p = 0.021).The PegIFNα/ribavirin/protease inhibitor combination is highly effective in severe and/or refractory HCV-MC at the cost of frequent side effects. Baseline platelet count and liver fibrosis are useful in guiding treatment decisions.

Objective Cardiac changes induced by scuba diving were investigated using Doppler echocardiography. Material and methods Ten healthy scuba divers dove to a mean depth of 34.3 ± 2.7 m of sea water (113 ± 9 feet) and a mean duration of 25.3 ± 3.5 min. Results One hour after the dive, microbubbles could be detected in the right-heart chambers of all subjects. Left atrial and left ventricular (LV) diameters significantly decreased after the dive. Cardiac output, assessed by aortic blood flow, remained unchanged. Heart rate increased and stroke volume (SV) decreased after the dive. LV filling was assessed on transmitral profile. An increase of the contribution of the atrial contraction to LV filling was observed. Right cavity diameters were unchanged, but an increase of the right ventricular/right atrial gradient pressure was found. Conclusion The diving profile studied promotes a rather important bubble grade in all volunteers. A significantly reduced cardiac diameters and SV was found by our hemodynamic study 1 h after diving. Two factors can explain these results: low volemia secondary to immersion, and venous gas embolism induced by nitrogen desaturation. Consequently, restoration of the water balance of the body should be considered in the recovery process after diving.

Predictive factors for alcoholic relapse after liver transplantation (LT) performed for alcoholic liver disease (ALD) have been assessed in numerous studies, often with contradictory results. The aim of the study was to assess pretransplantation alcohol consumption characteristics on alcoholic relapse after LT. Patients transplanted for ALD for at least 6 months were included. An anonymous questionnaire assessed socio-demographic characteristics, medical history, and alcohol consumption before and after LT. Relapse was defined as any alcohol use after LT. Severe relapse was defined by heavy drinking: more than 21 units/week for males and 14 units/week for females. A total of 61 patients were studied. The mean follow up after LT was 49 +/- 34 months. Alcoholic relapse occurred in 32 of 61 patients (52%) and severe relapse in eight of 61 patients (13%). Risk factors for severe relapse were: length of abstinence before LT (P = 0.0001), more than one alcohol withdrawal before LT (P = 0.001), alcohol dependence (P = 0.05), alcohol abuse in first relatives (P = 0.05), and younger age (P = 0.05). Information on previous alcohol consumption (dependence, number of withdrawals, family history) helps to predict severe relapse after LT in patients with ALD, allowing early awareness and specific postoperative care.

Background: The association between chronic alcohol consumption and an increasing risk of infectious and neoplastic disease is related to an impairment of cellular immunity. However, studies of the number and activity of lymphocyte subsets show highly variable results. The aim of this study was to assess the expression of perforin, one of the main molecular agents of T and natural killer (NK) cell–mediated cytotoxicity, in alcoholic patients without cirrhosis. Methods: Eighteen patients with chronic alcoholism were prospectively included and compared with 18 age- and sex-matched healthy volunteers. Signs of hepatic insufficiency or portal hypertension, viral co-infection, other serious medical illness, and immune-related medications were exclusion criteria. Lymphocyte phenotype was assessed, and perforin expression was analyzed by flow cytometry in CD3+CD56+ T cells and NK cells. Granzyme synthesis was also evaluated in 11 of the 18 patients and compared with that of 11 age- and sex-matched controls. Results: The mean number of white blood cells and lymphocytes was not different between the controls and alcoholic patients, whereas the mean number of NK cells was significantly decreased in alcoholic patients (110 ± 79/mm3 versus 271 ± 192/mm3; p < 0.03). Perforin expression in T CD3+/CD56+ and in NK cells was significantly decreased in alcoholic patients compared with controls: 16 ± 3% vs. 36 ± 4% (p < 0.03) and 65 ± 15% vs. 78 ± 9% (p= 0.04), respectively. The percentage of cells expressing granzyme was similar in both groups. Conclusions: A decrease in perforin expression by cytotoxic cells could be a major factor in explaining the physiopathologic mechanisms of several alcohol-associated diseases.

Inert gas narcosis is a neurological syndrome appearing when humans or animals are exposed to hyperbaric inert gases (nitrogen, argon) composed by motor and cognitive impairments. Inert gas narcosis induces a decrease of the dopamine release at the striatum level, structure involved in the regulation of the extrapyramidal motricity. We have investigated, in freely moving rats exposed to different narcotic conditions, the relationship between the locomotor and motor activity and the striatal dopamine release, using respectively a computerized device that enables a quantitative analysis of this behavioural disturbance and voltammetry. The use of 3 MPa of nitrogen, 2 MPa of argon and 0.1 MPa of nitrous oxide, revealed after a transient phase of hyperactivity, a lower level of the locomotor and motor activity, in relation with the decrease of the striatal dopamine release. It is concluded that the striatal dopamine decrease could be related to the decrease of the locomotor and motor hyperactivity, but that other(s) neurotransmitter(s) could be primarily involved in the behavioural motor disturbances induced by narcotics. This biphasic effect could be of major importance for future pharmacological investigations, and motor categorization, on the basic mechanisms of inert gas at pressure.

The Montagu's Harrier (MH) and the Lesser Kestrel (LK) are two threatened raptors overwintering in the Sahel. To ensure their conservation, it is essential to gain better knowledge on their winter ecology in order to predict their spatial distribution and estimate their respective population sizes. Combining information on raptors, their prey and habitats, collected over the 2009-2013 period in a 17,000 km(2) study area located in central Senegal, we assessed spatio-temporal variations of grasshopper density, and consequently estimated the abundance and distribution of MHs and LKs. The distribution of grasshoppers highlighted areas with contrasted densities, declining along a North East/South West gradient which constrained the spread of raptors. Moreover both species selected heterogeneous landscapes of savannah, mixing semi-natural and anthropogenized habitats. Population size reached 3360 and 36,000 individuals for MH and LK, which represents similar to 5% and 50% of their European breeding populations. The challenge for their conservation resides in their use of habitats suffering from anthropogenic perturbations, both during breeding and wintering. In Africa, this situation will be exacerbated in the near future due to interactions between food security, implying the control of grasshopper outbreaks and agricultural intensification, and to ongoing climate changes. (C) 2014 Elsevier Ltd. All rights reserved.

BACKGROUND—Liver iron deposits are frequent in viral C cirrhotic patients but their role is not well defined. AIMS—To investigate the effect of liver iron excess on the prevalence of hepatocellular carcinoma (HCC) in patients with viral C cirrhosis. METHODS—Hepatic iron was evaluated retrospectively using a semiquantitative method in liver biopsies of 104 viral C cirrhotic patients, 48 with HCC and 56 controls (HCC free). Corrected total iron score (0-60) was defined by the sum of three scores: hepatocytic iron score (0-36), sinusoidal iron score (0-12), and portal iron score (0-12), multiplied by 3/3, 2/3, or 1/3 according to the heterogeneous iron localisation in the nodules. RESULTS—After adjustment for known risk factors for HCC, regression analysis showed that iron deposits (corrected total iron score >0) were more frequent in HCC patients than in controls (odds ratio 4.94; 95% confidence interval 1.59-15.32; p=0.0056). The median of corrected total iron score was significantly higher in HCC patients than in controls (odds ratio 1.092; 95% confidence interval 1.01-1.13; p=0.021). This liver iron overload was sinusoidal (odds ratio 5.2; 95% confidence interval 1.82-15.11; p=0.0022). CONCLUSIONS—Liver iron deposition was more frequent and more important in viral C cirrhotic patients with HCC than in HCC free controls. Liver iron overload seems to contribute to the development of HCC in patients with viral C cirrhosis. Keywords: liver; iron; viral C cirrhosis; hepatocellular carcinoma

Although the efficacy of 5-fluorouracil (5-FU) modulated by leucovorin is well established for advanced colorectal cancer, the question of the most effective regimen and optimal dose of leucovorin remains unanswered. This prospective randomized trial compares low-dose (group 1) and high-dose (group 2) leucovorin, combined with the same dose of 5-FU to determine whether high-dose leucovorin was more beneficial than low-dose on overall survival. Inclusion criteria were: unresectable metastatic colorectal carcinoma, with or without evaluable tumor response; a performance status of less than grade 3 (World Health Organization classification); and no previous chemotherapy for metastases. Forty-two patients were randomized in group 1 (leucovorin, 20 mg/m2/day, days 1 through 5) and 41 patients in group 2 (leucovorin, 200 mg/m2/day, days 1-5). All the patients in the two groups received a 1-hour infusion of 400 mg/m2/day 5-FU every 4 weeks. The two groups were matched with no statistically significant differences in gender ratio, site of primary tumor, performance status, and tumor extent. Toxicity in the two regimens was low and not significantly different between the two groups. Overall median survival was 346 days in group 1 and 323 days in group 2 and was not significantly different between the two groups. At 1 year, the test of equivalence was significant (p < 0.01), demonstrating an absence of more than 20% benefit in 1-year survival for the high-dose regimen. The use of high-dose leucovorin combined with 5-FU in the 5-day regimen does not significantly improve overall survival for patients who have metastatic colorectal cancer.

BACKGROUND/AIM The risk of adverse drug interactions with interferon-alpha has been poorly assessed. The aim of our study was to establish whether administration of interferon-alpha at therapeutic doses in patients with chronic hepatitis C may have significant inhibitory effects on other drug metabolism. The study was focused on cytochromes P-450 1A2 and 3A, two major isoforms involved in the metabolism of numerous substrates. METHODS Eighteen patients with chronic active hepatitis C requiring an interferon-alpha treatment were studied. Cytochrome P-450 1A2 activity was determined on the basis of an in vivo caffeine metabolism study. Cytochrome P-450 3A activity was determined according to in vivo cortisol metabolism into 6-beta-hydroxycortisol. Both activities were determined 1 month before, at initiation and 1 month after interferon-alpha therapy (3 x 10(6) units, three times a week). RESULTS There were no significant differences in the caffeine index (CYP 1A2) and in the 6-beta-hydroxycortisol/free cortisol urinary ratio (CYP 3A) before and after alpha interferon treatment CONCLUSION Chronic administration of interferon-alpha at therapeutic doses does not change in vivo cytochrome P-450 1A2 and 3A activities. These results support the suggestion that drugs metabolized by these isoenzymes may be used together with interferon-alpha in patients with chronic hepatitis C without significant risks of drug interactions.

Purpose We assessed the resistance index (RI) in the superior mesenteric artery under fasting and postprandial conditions in healthy subjects and in patients with cirrhosis to determine whether the amount of change in the RI reflects the presence or severity of liver dysfunction. Methods Fifteen subjects with normal livers and 27 patients with cirrhosis underwent Doppler sonography of the superior mesenteric artery before and after ingesting a standard meal. The RI at baseline (fasting state) and the postprandial RI were compared between the 2 groups. The fasting RIs and post postprandial RIs changes in cirrhotic patients were correlated with the severity of disease. Results No difference was found between the baseline RIs in healthy (RI = 0.85) and cirrhotic subjects (RI = 0.84), nor was there a difference in baseline RIs between subgroups of cirrhotic patients according to the severity of liver disease. The RI decreased significantly (p < 0.05) after the meal in both the healthy (13%) and cirrhotic (8%) subjects, but the postprandial decrease was significantly less pronounced (p < 0.05) in cirrhotic patients than in healthy subjects. Among cirrhotic patients, there was no correlation between the postprandial decrease of the RI and severity of liver disease. Conclusions The marked decrease in the postprandial RI in the SMA in healthy subjects is generally not seen in patients with cirrhosis, and changes in the postprandial RI do not reliably predict the severity of liver dysfunction. © 1998 John Wiley & Sons, Inc. J Clin Ultrasound 26:131–136, 1998.

Increased plasma and CSF concentrations of substances which bind to brain benzodiazepine receptors have previously been reported in cirrhotic patients with hepatic encephalopathy (HE). However, their relationship to previous intake of pharmaceutical benzodiazepines has not been clearly established. In the present study, plasma levels of benzodiazepine receptor ligands (BZRLs) were measured using a sensitive radioreceptor assay in 12 control subjects with no evidence of hepatic, neurological or psychiatric illness, 11 cirrhotic patients without HE, 24 cirrhotic patients with moderate (grade I-II) HE and in 45 cirrhotic patients with severe (grade II-IV) HE. In addition, CSF concentrations of BZRLs were measured in 8 cirrhotic patients with HE and an equal number of age-matched controls. Recent intake (within 10 days) of pharmaceutical benzodiazepines was assessed by detailed review of medical files, and interviews with the patient, at least one family member as well as the pharmacist. Significantly increased plasma concentrations of BZRLs were observed in cirrhotic patients with severe encephalopathy (p

In diesem Beitrag untersucht der Verfasser die Zusammenhange, die sich zwischen dem Umstrukturierungsprozess der Uhrenindustrie in der Schweiz und der Errichtung neuer Uhrenproduktions- und -exportstatten in den Schwellenlandern Asiens (Hongkong, Sudkorea, Taiwan und Singapur) ergeben. Er geht dabei von der Tatsache aus, dass der in den vergangenenen Jahren eingetretene technologische Wandel weltweit zu einer Umverteilung der Uhrenindustrie (Verlagerung in die Billiglohnlander) gefuhrt hat.Im ersten Teil wird der Uhrenhandel zwischen der Schweiz und den asiatischen Schwellenlandern untersucht. Dabei werden folgende Tendenzen festgestellt : Ab 1970 bedeutende Einfuhren von Billiguhren und Uhrenbestandteilen aus den asiatischen Schwellenlandern (und anderen asiatischen Landern). Bis 1980 umfangreiche schweizerische Lieferungen an Uhrenbestandteilen in diese neuen Produktionsstatten, danach Ruckgang dieses Trends. Seit einigen Jahren ein gewisser Wiederaufschwung des Schweizer Uhrenexports (vor allem elektronische Uhren), nach einem langwierigen Umstrukturierungsprozess der schweizerischen Uhrenindustrie.Im zweiten Teil wird die Niederlassungspolitik der Schweizer Uhrenindustrie in den asiatischen Schwellenlandern analysiert. An der Fallstudie Hongkong wird gezeigt, dass die Produktionsverlagerung zu einem relativ spaten Zeitpunkt und in beschranktem Ausmass erfolgte. Dies lasst sich durch die besondere Struktur der Schweizer Uhrenindustrie (langsames Vordringen der neuen Technologien, Ruckgang der Marktprasenz, starker Beschaftigungsruckgang in der Branche ) erklaren.In seinen Schlussfolgerungen fuhrt der Verfasser am Beispiel Hongkongs eine Reihe von Grunden an, die eine nuancierte Bewertung der Bemuhungen der Schweizer Uhrenindustrie zur Produktionsverlagerung in die asiatischen Schwellenlandern ratsam erscheinen lassen. Er kommt zu dem Schluss, dass sich statt einer Opposition zwischen den jungen asiatischen Industrielandern und den traditionellen Industriestaaten derzeit eine Tendenz zur wachsenden internationalen Arbeitsteilung in der Uhren Industrie abzeichnet ; hierbei scheint Hongkong eine mittlere Position zwischen den modernen Forschungs- und Entwicklungszentren (Japan, Schweiz) und den „Wirtschaftszonen” der Billiglohnlander (China, Thailand, Malaysia und Philippinen) einzunehmen.

International audience; Numerical computation of Nonlinear Normal Modes (NNMs) for conservative vibratory systems is addressed, with the aim of deriving accurate reduced-order models up to large amplitudes. A numerical method is developed, based on the center manifold approach for NNMs, which uses an interpretation of the equations as a transport problem, coupled to a periodicity condition for ensuring manifold's continuity. Systematic comparisons are drawn with other numerical methods, and especially with continuation of periodic orbits, taken as reference solutions. Three di erent mechanical systems, displaying peculiar characteristics allowing for a general view of the performance of the methods for vibratory systems, are selected. Numerical results show that invariant manifolds encounter folding points at large amplitude, generically (but not only) due to internal resonances. These folding points involve an intrinsic limitation to reduced-order models based on the center manifold and on the idea of a functional relationship between slave and master coordinates. Below that amplitude limit, numerical methods are able to produce reduced-order models allowing for a precise prediction of the backbone curve.

The paper presents the role of DSOs in future energy, capacity and balancing markets. DSO will have a role of market facilitator for decentralized generation and demand response, and will enable local optimization while fulfilling its traditional mission of safety of distribution networks. The French electric system faces two challenges: - A steady growth of peak demand at system level and on local networks, which can be aggravated by the upcoming of Electric Vehicles - Growth of the proportion of intermittent and decentralized generation in its electric mix. It is therefore of high importance that the electric system rely more and more on decentralized generation and demand response to address these balancing issues. Since these resources are connected to the distribution networks, DSOs are key to contribute to the management of a local system as part of a national optimization: - DSO is a technical contract holder with network capacities - DSO collects information regarding the Balancing Responsible Party and manage metering data - DSO supervises flows on its network and is responsible of its safety, - DSO is an independent party with nondiscrimination objectives DSO plays therefore a key role in the creation and handling of the aggregates that can be traded on these markets at 3 key times: certification, activation and evaluation. Based on its experience, ERDF shows the benefit for the stakeholders of its key contribution. (4 pages)

Bilateral administration of NMDA (5×10 −10 mol) in the substantia nigra pars compacta increases the striatal dopamine (DA) release. However, this enhancing effect of NMDA was suppressed by nitrous oxide exposure at 0.1 MPa, which induced per se a decrease of the DA release. These results show that nitrous oxide exerts a reversal effect on the increase in striatal DA release produced by NMDA receptor activation in the substantia nigra pars compacta. This observation may be related to the fact that nitrous oxide is thought to produce its effects by acting as an NMDA receptor antagonist.

We report 3 cases of bullous immunoglobulinic amyloidosis and review 25 published cases. In 2 of our patients, amyloid deposits were not detected with special staining, but by means of ultrastructural methods. Investigations of the skin lesions permitted the diagnosis of associated plasma cell dyscrasia in 2 patients. Unexplained bullous lesions should be investigated for amyloid deposits and the presence of monoclonal gammopathy by methods including electron microscopy and immunochemical analysis of serum and urine.

We studied 70 patients with biopsy-proven pulmonary non-Hodgkin's lymphomas without extrathoracic involvement or mediastinal adenopathy to determine the clinical, imaging, and endoscopic features of this condition in a homogeneous series. In low-grade (LG) lymphomas, symptoms were cough, dyspnea, chest pain, hemoptysis. Imaging features consisted of localized alveolar opacities, infiltrative diffuse opacities, atelectasis, and pleural effusions. Inflammatory changes of the mucosa were present in some patients, leading to bronchial stenosis in 7; biopsies showed lymphomatous infiltration in 12. Prognosis of LG lymphomas was excellent, with 93.6 percent survival at five years. High-grade lymphomas differed from LG lymphomas principally by a more aggressive course and a worse survival. Inflammatory changes occurred in seven of nine cases leading to stenosis in two, and biopsies showed lymphomatous involvement in five. The profile of primary pulmonary lymphomas in this study could help clinicians consider this condition and prompt them to evaluate new diagnostic tools.