Plume motion and large-scale circulation in a cylindrical Rayleigh-B\'enard cell

We used the time correlation of shadowgraph images to determine the angle $\Theta$ of the horizontal component of the plume velocity above (below) the center of the bottom (top) plate of a cylindrical Rayleigh-B\'enard cell of aspect ratio $\Gamma \equiv D/L = 1$ ($D$ is the diameter and $L \simeq 87$ mm the height) in the Rayleigh-number range $7\times 10^7 \leq R \leq 3\times 10^{9}$ for a Prandtl number $\sigma = 6$. We expect that $\Theta$ gives the direction of the large-scale circulation. It oscillates time-periodically. Near the top and bottom plates $\Theta(t)$ has the same frequency but is anti-correlated.Comment: 4 pages, 6 figure

Patterns of chromosomal copy-number alterations in intrahepatic cholangiocarcinoma

International audienceBackground: Intrahepatic cholangiocarcinomas (ICC) are relatively rare malignant tumors associated with a poor prognosis. Recent studies using genome-wide sequencing technologies have mainly focused on identifying new driver mutations. There is nevertheless a need to investigate the spectrum of copy number aberrations in order to identify potential target genes in the altered chromosomal regions. The aim of this study was to characterize the patterns of chromosomal copy-number alterations (CNAs) in ICC. Methods: 53 patients having ICC with frozen material were selected. In 47 cases, DNA hybridization has been performed on a genomewide SNP array. A procedure with a segmentation step and a calling step classified genomic regions into copy-number aberration states. We identified the exclusively amplified and deleted recurrent genomic areas. These areas are those showing the highest estimated propensity level for copy loss (resp. copy gain) together with the lowest level for copy gain (resp. copy loss). We investigated ICC clustering. We analyzed the relationships between CNAs and clinico-pathological characteristics. Results: The overall genomic profile of ICC showed many alterations with higher rates for the deletions. Exclusively deleted genomic areas were 1p, 3p and 14q. The main exclusively amplified genomic areas were 1q, 7p, 7q and 8q. Based on the exclusively deleted/amplified genomic areas, a clustering analysis identified three tumors groups: the first group characterized by copy loss of 1p and copy gain of 7p, the second group characterized by 1p and 3p copy losses without 7p copy gain, the last group characterized mainly by very few CNAs. From univariate analyses, the number of tumors, the size of the largest tumor and the stage were significantly associated with shorter time recurrence. We found no relationship between the number of altered cytobands or tumor groups and time to recurrence. Conclusion: This study describes the spectrum of chromosomal aberrations across the whole genome. Some of the recurrent exclusive CNAs harbor candidate target genes. Despite the absence of correlation between CNAs and clinico-pathological characteristics, the co-occurence of 7p gain and 1p loss in a subgroup of patients may suggest a differential activation of EGFR and its downstream pathways, which may have a potential effect on targeted therapies

Early tumour response as a survival predictor in previously- treated patients receiving triplet hepatic artery infusion and intravenous cetuximab for unresectable liver metastases from wild-type KRAS colorectal cancer

Background: Early tumour shrinkage has been associated with improved survival in patients receiving cetuximab-based systemic chemotherapy for liver metastases from colorectal cancer (LM-CRC). We tested this hypothesis for previously treated LM-CRC patients receiving cetuximab (500 mg/m2) and triplet hepatic artery infusion (HAI) within European trial OPTILIV. Methods: Irinotecan (180 mg/m2), 5-fluorouracil (2800 mg/m2) and oxaliplatin (85 mg/m2) were given as chronomodulated or conventional delivery. Patients were retrospectively categorised as early responders (complete or partial RECIST response after three courses) or non-early responders (late or no response). Prognostic factors were determined using multivariate logistic or Cox regression models. Results: Response was assessed in 57 of 64 registered patients (89%), who had previously received one to three prior systemic chemotherapy protocols. An early response occurred at 6 weeks in 16 patients (28%; 9 men, 7 women), aged 33–76 years, with a median of 12 liver metastases (LMs) (2–50), involving five segments (1–8). Ten patients had a late response, and 31 patients had no response. Grade 3–4 fatigue selectively occurred in the non-early responders (0% versus 26%; p = 0.024). Early tumour response was jointly predicted by chronomodulation—odds ratio (OR): 6.0 (1.2–29.8; p = 0.029)—and LM diameter ≤57 mm—OR: 5.3 (1.1–25.0; p = 0.033). Early tumour response predicted for both R0-R1 liver resection—OR: 11.8 (1.4–100.2; p = 0.024) and overall survival—hazard ratio: 0.39 (0.17–0.88; p = 0.023) in multivariate analyses. Conclusions: Early tumour response on triplet HAI and systemic cetuximab predicted for complete macroscopic liver resection and prolonged survival for LM-CRC patients within a multicenter conversion-to-resection medicosurgical strategy. Confirmation is warranted for early response on HAI to guide decision making

Sequential versus combination chemotherapy for the treatment of advanced colorectal cancer (FFCD 2000-05): an open-label, randomised, phase 3 trial

BACKGROUND: The optimum use of cytotoxic drugs for advanced colorectal cancer has not been defined. Our aim was to investigate whether combination treatment is better than the sequential administration of the same drugs in patients with advanced colorectal cancer. METHODS: In this open-label, randomised, phase 3 trial, we randomly assigned patients (1:1 ratio) with advanced, measurable, non-resectable colorectal cancer and WHO performance status 0-2 to receive either first-line treatment with bolus (400 mg/m(2)) and infusional (2400 mg/m(2)) fluorouracil plus leucovorin (400 mg/m(2)) (simplified LV5FU2 regimen), second-line LV5FU2 plus oxaliplatin (100 mg/m(2)) (FOLFOX6), and third-line LV5FU2 plus irinotecan (180 mg/m(2)) (FOLFIRI) or first-line FOLFOX6 and second-line FOLFIRI. Chemotherapy was administered every 2 weeks. Randomisation was done centrally using minimisation (minimisation factors were WHO performance status, previous adjuvant chemotherapy, number of disease sites, and centre). The primary endpoint was progression-free survival after two lines of treatment. Analyses were by intention-to-treat. This trial is registered at ClinicalTrials.gov, NCT00126256. FINDINGS: 205 patients were randomly assigned to the sequential group and 205 to the combination group. 161 (79%) patients in the sequential group and 161 (79%) in the combination group died during the study. Median progression-free survival after two lines was 10·5 months (95% CI 9·6-11·5) in the sequential group and 10·3 months (9·0-11·9) in the combination group (hazard ratio 0·95, 95% CI 0·77-1·16; p=0·61). All six deaths caused by toxic effects of treatment occurred in the combination group. During first-line chemotherapy, significantly fewer severe (grade 3-4) haematological adverse events (12 events in 203 patients in sequential group vs 83 events in 203 patients in combination group; p<0·0001) and non-haematological adverse events (26 events vs 186 events; p<0·0001) occurred in the sequential group than in the combination group. INTERPRETATION: Upfront combination chemotherapy is more toxic and is not more effective than the sequential use of the same cytotoxic drugs in patients with advanced, non-resectable colorectal cancer. FUNDING: Sanofi-Aventis France

Report of depressive symptoms on waiting list and mortality after liver and kidney transplantation: a prospective cohort study

International audienceABSTRACT: BACKGROUND: Little research has explored pre-transplantation psychological factors as predictors of outcome after liver or kidney transplantation. Our objective is to determine whether report of depressive symptoms on waiting list predicts outcome of liver and kidney transplantation. METHODS: Patients on waiting list for liver or kidney transplantation were classified for report or non-report of depressive symptoms on waiting list. 339 were transplanted 6 months later on average, and followed prospectively. The main outcome measures were graft failure and mortality 18 months post-transplantation. RESULTS: Among the 339 patients, 51.6% reported depressive symptoms on waiting list, 16.5% had a graft failure and 7.4% died post-transplantation. Report of depressive symptoms on waiting list predicted a 3 to 4-fold decreased risk of graft failure and mortality 18-months post-transplantation, independently from age, gender, current cigarette smoking, anxiety symptoms, main primary diagnosis, UNOS score, number of comorbid diagnoses and history of transplantation. Data were consistent for liver and kidney transplantations. Other baseline predictive factors were: for graft failure, the main primary diagnosis and a shorter length since this diagnosis, and for mortality, older age, male gender and the main primary diagnosis. CONCLUSION: Further studies are needed to understand the underlying mechanisms of the association between report of depressive symptoms on waiting list and decreased risk of graft failure and mortality after transplantation

Quelques remarques sur l'adhésion de l'Italie au Pacte Atlantique

Denis Castaing, Quelques remarques sur l'adhésion de l'Italie au Pacte Atlantique, p. 491-501. L'Italie, libérée et occupée par les troupes anglo-américaines ne pouvait pas, d'une manière ou d'une autre, ne pas adhérer au Pacte Atlantique. L'Italie avait été considérée comme un «satellite de l'Allemagne» vaincu, et le traité de Paris (1947) lui avait été imposé. Pour De Gasperi, Président du Conseil, et Sforza, Ministre des Affaires Étrangères, être parmi les premiers signataires du Pacte (4 Avril 1949) signifiait aussi la problable caducité des clauses restrictives du Traité de Paris à brève échéance (en fait, 1952) et la réinsertion complète de l'Italie dans l'Europe occidentale (pour eux foyer de progrès et de démocratie) après l'isolement de la période fasciste. La décision politique a été prise par ces deux hommes, qui ont mis devant le fait presque accompli leurs propres partis et le parlement quelques jours avant la signature. Cependant, l'approbation des ministres et du parlement, l'absence de grandes manifestations d'opposition et les résultats de plusieurs sondages tendent à montrer que les Italiens n'étaient pas, en majorité, hostiles au choix des gouvernants.Castaing Denis. Quelques remarques sur l'adhésion de l'Italie au Pacte Atlantique. In: Mélanges de l'Ecole française de Rome. Moyen-Age, Temps modernes, tome 90, n°1. 1978. pp. 491-501

Traitements des obstructions biliaires symptomatiques dans le caverne portal

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF