Lien entre durée de séjour et réadmissions en chirurgie et en obstétrique: étude de deux procédures à partir des données du PMSI = Using administrative data to assess the impact of length of stay on readmissions: study of two procedures in surgery and obstetrics

Position du problème: La mise en place de la tarification à l'activité pour les hôpitaux de court séjour pourrait entraîner une diminution des durées de séjour pour raisons financières. L'impact potentiel de ce phénomène sur la qualité des soins n'est pas connu. Les réadmissions identifiées à l'aide des données administratives hospitalières sont, pour certaines situations cliniques, des indicateurs de qualité des soins valides. Méthode: Étude rétrospective du lien entre la durée de séjour et la survenue de réadmissions imprévues liées au séjour initial, pour les cholécystectomies simples et les accouchements par voie basse sans complication, à partir des données du programme de médicalisation des systèmes d'information de l'Assistance publique-Hôpitaux de Paris des années 2002 à 2005. Résultats: Pour les deux procédures, la probabilité de réadmission suit une courbe en " J ". Après ajustement sur l'âge, le sexe, les comorbidités associées, l'hôpital et l'année d'admission, la probabilité de réadmission est plus élevée pour les durées de séjour les plus courtes : pour les cholécystectomies, odds ratio : 6,03 [IC95 % : 2,67-13,59] pour les hospitalisations d'un jour versus trois jours ; pour les accouchements, odds ratio : 1,74 [IC95 % : 1,05-2,91] pour les hospitalisations de deux jours versus trois jours. Conclusion: Pour deux pathologies communes, les durées de séjour les plus courtes sont associées à des probabilités de réadmission plus élevées. L'utilisation routinière des données du programme de médicalisation des systèmes d'information peut permettre d'assurer le suivi de la relation entre la réduction de la durée de séjour et les réadmissions. The prospective payment system for the French short-stay hospitals creates a financial incentive to reduce length of stay. The potential impact of the resulting decrease in length of stay on the quality of healthcare is unknown. Readmission rates are valid outcome indicators for some clinical procedures. Methods: Retrospective study of the association between length of stay and unplanned readmissions related to the initial stay, for two procedures: cholecystectomy and vaginal delivery. Data: Administrative diagnosis-related groups database of "Assistance publique-Hopitaux de Paris", a large teaching hospital, for years 2002 to 2005. Results: The risk of readmission according to length of stay, taking age, sex, comorbidity, hospital and year of admission into account, followed a J-shaped curve for both procedures. The probability of readmission was higher for very short stays, with odds ratios and 95% confidence intervals of 6.03 [2.67-13.59] for cholecystectomies (1- versus 3-night stays), and of 1.74 [1.05-2.91] for vaginal deliveries (2- versus 3-night stays). Conclusion: For both procedures, the shortest lengths of stay are associated with a higher readmission probability. Suitable indicators derived from administrative databases would enable monitoring of the association between length of stay and readmissions.

Does abdominoplasty with liposuction of the love handles yield a shorter scar? An analysis with abdominal 3D laser scanning.

The aim of this study was to evaluate the combination of abdominoplasty with liposuction of both flanks with regards to length of scar, complications, and patient's satisfaction. A retrospective analysis of 35 patients who underwent esthetic abdominoplasty at our institution between 2002 and 2004 was performed. Thirteen patients underwent abdominoplasty with liposuction of both flanks, 22 patients underwent conventional abdominoplasty. Liposuction of the flanks did not increase the rate of complications of the abdominoplasty procedures. We found a tendency toward shorter scars in patients who underwent abdominoplasty combined with liposuction of the flanks. Implementation of 3-dimensional laser surface scanning to objectify the postoperative outcomes, documented a comparable degree of flatness of the achieved body contouring in both procedures. 3-dimensional laser surface scanning can be a valuable tool to objectify assessment of postoperative results.

Association of moderate alcohol use and binge drinking during pregnancy with neonatal health.

Background:  Heavy drinking and smoking during pregnancy are known to have a negative impact on the unborn child. However, the impact of low-to-moderate alcohol consumption and binge drinking has been debated recently. The aim of this study was to examine the relationship of moderate prenatal drinking and binge drinking with birthweight, being small for gestational age (SGA) at birth, preterm birth, and neonatal asphyxia. Methods:  Moderate alcohol drinking, binge drinking, and several possible confounders were assessed in 1,258 pregnant women; information on neonatal health was obtained at birth. Results:  Results indicate that 30.8% of the women drank at low levels (<2 glasses/wk), 7.9% drank moderately (2 to 4 glasses/wk), and 0.9% showed higher levels of drinking (≥5 glasses/wk); 4.7% reported binge drinking (defined as ≥3 glasses/occasion). 6.4% of the children were SGA (<10th percentile of birthweight adjusted for gestational age), 4.6% were preterm (<37th week of gestation), and 13.0% showed asphyxia (arterial cord pH <7.10 and/or arterial cord lactate >6.35 mmol and/or Apgar score <7 at 5 minutes). When controlling for maternal age, citizenship, occupational status, parity, smoking, use of prescription/over-the-counter drugs, illicit drug use, and child gender moderate drinking was related to lower birthweight (p < 0.01), and moderate drinking and binge drinking were associated with neonatal asphyxia at trend level (p = 0.06 and p = 0.09). Moderate drinking and binge drinking were not related to length of gestation. Conclusions:  In contrast to recent reviews in the field, our results assume that moderate drinking and binge drinking are risk factors for neonatal health.

Quantitative modelling of transcription factor binding sites

Abstract One of the most important issues in molecular biology is to understand regulatory mechanisms that control gene expression. Gene expression is often regulated by proteins, called transcription factors which bind to short (5 to 20 base pairs),degenerate segments of DNA. Experimental efforts towards understanding the sequence specificity of transcription factors is laborious and expensive, but can be substantially accelerated with the use of computational predictions. This thesis describes the use of algorithms and resources for transcriptionfactor binding site analysis in addressing quantitative modelling, where probabilitic models are built to represent binding properties of a transcription factor and can be used to find new functional binding sites in genomes. Initially, an open-access database(HTPSELEX) was created, holding high quality binding sequences for two eukaryotic families of transcription factors namely CTF/NF1 and LEFT/TCF. The binding sequences were elucidated using a recently described experimental procedure called HTP-SELEX, that allows generation of large number (> 1000) of binding sites using mass sequencing technology. For each HTP-SELEX experiments we also provide accurate primary experimental information about the protein material used, details of the wet lab protocol, an archive of sequencing trace files, and assembled clone sequences of binding sequences. The database also offers reasonably large SELEX libraries obtained with conventional low-throughput protocols.The database is available at http://wwwisrec.isb-sib.ch/htpselex/ and and ftp://ftp.isrec.isb-sib.ch/pub/databases/htpselex. The Expectation-Maximisation(EM) algorithm is one the frequently used methods to estimate probabilistic models to represent the sequence specificity of transcription factors. We present computer simulations in order to estimate the precision of EM estimated models as a function of data set parameters(like length of initial sequences, number of initial sequences, percentage of nonbinding sequences). We observed a remarkable robustness of the EM algorithm with regard to length of training sequences and the degree of contamination. The HTPSELEX database and the benchmarked results of the EM algorithm formed part of the foundation for the subsequent project, where a statistical framework called hidden Markov model has been developed to represent sequence specificity of the transcription factors CTF/NF1 and LEF1/TCF using the HTP-SELEX experiment data. The hidden Markov model framework is capable of both predicting and classifying CTF/NF1 and LEF1/TCF binding sites. A covariance analysis of the binding sites revealed non-independent base preferences at different nucleotide positions, providing insight into the binding mechanism. We next tested the LEF1/TCF model by computing binding scores for a set of LEF1/TCF binding sequences for which relative affinities were determined experimentally using non-linear regression. The predicted and experimentally determined binding affinities were in good correlation.

Application of a roughness-length representation to parameterize energy loss in 3-D numerical simulations of large rivers

Recent technological advances in remote sensing have enabled investigation of the morphodynamics and hydrodynamics of large rivers. However, measuring topography and flow in these very large rivers is time consuming and thus often constrains the spatial resolution and reach-length scales that can be monitored. Similar constraints exist for computational fluid dynamics (CFD) studies of large rivers, requiring maximization of mesh-or grid-cell dimensions and implying a reduction in the representation of bedform-roughness elements that are of the order of a model grid cell or less, even if they are represented in available topographic data. These ``subgrid'' elements must be parameterized, and this paper applies and considers the impact of roughness-length treatments that include the effect of bed roughness due to ``unmeasured'' topography. CFD predictions were found to be sensitive to the roughness-length specification. Model optimization was based on acoustic Doppler current profiler measurements and estimates of the water surface slope for a variety of roughness lengths. This proved difficult as the metrics used to assess optimal model performance diverged due to the effects of large bedforms that are not well parameterized in roughness-length treatments. However, the general spatial flow patterns are effectively predicted by the model. Changes in roughness length were shown to have a major impact upon flow routing at the channel scale. The results also indicate an absence of secondary flow circulation cells in the reached studied, and suggest simpler two-dimensional models may have great utility in the investigation of flow within large rivers. Citation: Sandbach, S. D. et al. (2012), Application of a roughness-length representation to parameterize energy loss in 3-D numerical simulations of large rivers, Water Resour. Res., 48, W12501, doi: 10.1029/2011WR011284.

Prédiction des durées de séjour en réadaptation en fonction du statut fonctionnel. [Usefulness of functional status to predict length of stay in rehabilitation.]

Objectif : En Suisse, la réadaptation est financée en¦partie par l'assureur qui fixe préalablement à l'admission¦un nombre de jours (durée garantie) qu'il s'engage¦à rembourser. Lorsqu'une durée garantie est trop courte,¦une demande de prolongation est nécessaire, induisant¦des démarches administratives. Les objectifs de cette¦étude étaient a) d'étudier le lien entre durées garanties¦et caractéristiques du patient ; b) d'estimer les coûts¦liés aux demandes de prolongation ; c) d'évaluer¦l'impact de l'introduction d'un modèle d'attribution de¦durée garantie basé sur l'état fonctionnel du patient.¦Méthodes : Les corrélations entre état fonctionnel,¦durée effective et durée garantie ont été testées sur¦208 séjours représentatifs. Des durées garanties fictives¦ont été calculées à partir de la médiane de durée de¦séjour de 2 335 patients, groupés selon leur niveau¦fonctionnel (score des activités de base de la vie quotidienne¦(BAVQ) 0-1 vs 2-4 vs 5-6), puis comparées aux¦durées de séjour effectives et garanties.¦Résultats : L'état fonctionnel du patient n'est pas¦corrélé à la durée garantie, et 69 % des séjours nécessitent¦au moins une demande de prolongation, représentant¦2,6 équivalents temps plein en temps administratif¦projeté sur le canton. L'application du modèle proposé¦réduirait de 28 % les demandes de prolongation, et¦n'augmenterait que marginalement la proportion de¦jours garantis en surplus (11,2 % contre 6,5 % actuellement).¦Conclusion : L'utilisation systématique d'un modèle¦d'attribution de durées garanties basées sur l'état¦fonctionnel du patient permettrait de réduire sensiblement¦les coûts administratifs liés aux demandes de¦prolongation, sans entraîner de risque accru d'une augmentation¦de la durée de séjour.

Determination of DNA persistence length by cryo-electron microscopy. Separation of the static and dynamic contributions to the apparent persistence length of DNA.

Axial deflection of DNA molecules in solution results from thermal motion and intrinsic curvature related to the DNA sequence. In order to measure directly the contribution of thermal motion we constructed intrinsically straight DNA molecules and measured their persistence length by cryo-electron microscopy. The persistence length of such intrinsically straight DNA molecules suspended in thin layers of cryo-vitrified solutions is about 80 nm. In order to test our experimental approach, we measured the apparent persistence length of DNA molecules with natural "random" sequences. The result of about 45 nm is consistent with the generally accepted value of the apparent persistence length of natural DNA sequences. By comparing the apparent persistence length to intrinsically straight DNA with that of natural DNA, it is possible to determine both the dynamic and the static contributions to the apparent persistence length.

Head-to-head comparison of length of stay, patients' outcome and satisfaction in Switzerland before and after SwissDRG-Implementation in 2012 in 2012: an observational study in two tertiary university centers.

On 1 January 2012 Swiss Diagnosis Related Groups (DRG), a new uniform payment system for in-patients was introduced in Switzerland with the intention to replace a "cost-based" with a "case-based" reimbursement system to increase efficiency. With the introduction of the new payment system we aim to answer questions raised regarding length of stay as well as patients' outcome and satisfaction. This is a prospective, two-centre observational cohort study with data from University Hospital Basel and the Cantonal Hospital Aarau, Switzerland, from January to June 2011 and 2012, respectively. Consecutive in-patients with the main diagnosis of either community-acquired pneumonia, exacerbation of COPD, acute heart failure or hip fracture were included. A questionnaire survey was sent out after discharge investigating changes before and after SwissDRG implementation. Our primary endpoint was LOS. Of 1,983 eligible patients 841 returned the questionnaire and were included into the analysis (429 in 2011, 412 in 2012). The median age was 76.7 years (50.8% male). Patients in the two years were well balanced in regard to main diagnoses and co-morbidities. Mean LOS in the overall patient population was 10.0 days and comparable between the 2011 cohort and the 2012 cohort (9.7 vs 10.3; p = 0.43). Overall satisfaction with care changed only slightly after introduction of SwissDRG and remained high (89.0% vs 87.8%; p = 0.429). Investigating the influence of the implementation of SwissDRG in 2012 regarding LOS patients' outcome and satisfaction, we found no significant changes. However, we observed some noteworthy trends, which should be monitored closely.

Treatment of penile carcinoma: to cut or not to cut?

PURPOSE: The aim of this study was to assess the outcome in patients with penile cancer. METHODS AND MATERIALS: A total of 60 patients with penile carcinoma were included. Of the patients, 45 (n = 27) underwent surgery, and 51 underwent definitive (n = 29) or postoperative (n = 22) radiotherapy (RT). Median follow-up was 62 months. RESULTS: Median time to locoregional relapse was 14 months. Local failure was observed in 3 of 23 patients (13%) treated with surgery with or without postoperative RT vs. in 19 of 33 patients (56%) given organ-sparing treatment (p = 0.0008). Of 22 local failures, 16 (73%) were salvaged with surgery. Of the 33 patients treated with definitive RT (n = 29) and the 4 patients refusing RT after excisional biopsy, local control was obtained with organ preservation in 13 (39%). In the remaining 20, 4 patients with local failure underwent salvage conservatively, resulting in an ultimate penis preservation rate of 17 of 33 (52%) patients treated with definitive RT. The 5-year and 10-year probability of surviving with an intact penis was 43% and 26%, respectively. There was no survival difference between the patients treated with definitive RT and primary surgery (56% vs. 53%; p = 0.16). In multivariate analysis, independent factors influencing survival were N-classification and pathologic grade. Surgery was the only independent predictor for better local control. CONCLUSION: Based on our study findings, in patients with penile cancer, local control is superior with surgery. However, there is no difference in survival between patients treated with surgery and those treated with definitive RT, with 52% organ preservation.

Phylogenetic relatedness and proboscis length contribute to structuring bumblebee communities in the extremes of abiotic and biotic gradients

Aim To improve our understanding of how biological communities assemble, we investigated changes in bumblebee communities in space along an elevation gradient. We assessed how much deterministic abiotic and biotic factors shape community assembly. We focused on proboscis length (influencing the species' dietary regime) and phylogenetic relatedness to investigate if competition and environmental filtering occur in more and less productive climates, respectively. Location Western Swiss Alps. Methods We recorded bumblebee species in 149 plots along a 1800-m wide elevation gradient. We contrasted two major clades of bumblebees, a short-tongued and a long-tongued clade. We calculated the phylogenetic and proboscis-length diversity of the bumblebee communities and compared these observed data with a random distribution to detect clustering likely to be caused by environmental filtering or overdispersion likely to be caused by competition. We compared the prevalence of clustered and overdispersed communities along the gradients of plant species richness (biotic) and temperature (abiotic). Results Under colder conditions, where plant species richness is lower and floral resources are scarcer, the clade with shorter proboscides prevails over the clade with longer proboscides, and communities are functionally and phylogenetic clustered. Under warmer conditions, we found phylogenetic but not functional overdispersion in communities. Main conclusions We show for the first time a strong correlation between phylogenetic relatedness, proboscis length and species distribution along temperature and plant richness gradients shaping bumblebee communities. The low temperatures and low levels of plant species richness limit the dispersal of the species from the long-tongued clade, which have more specialized diets, into high-elevation areas. Competition under warmer conditions may produce communities composed of less closely related species that share distinct ecological preferences. Our empirical results corroborate theoretical expectation as well as experiments on the prevalence of deterministic processes in the most severe and most productive parts of environmental gradients.

Benefits of endoscopic vein harvesting.

The purpose of this study was to evaluate and compare the benefits of endoscopic saphenous vein harvesting (EVH) with the traditional incision technique (TIT) for coronary artery bypass grafting (CABG) in respect to the technical procedure and clinical outcome. In a prospective nonrandomized, case-matched study the greater saphenous vein was harvested for CABG in 22 patients using the endoscopic technique and in 18 patients with the traditional method. Comparisons were made for the operating time, length of incision and vein harvested, graft quality, postoperative complications, and pain assessment. Patient demographics were well matched. EVH required smaller incisions than did the TIT (10.5 +/- 6.6 vs. 31.2 +/- 7.8 cm, respectively; p < 0.0001). Harvest time and vein quality were comparable in the two groups. Total vein operating time was shorter following the endoscopic technique (60 +/- 24 vs. 100 +/- 35 minutes, respectively; p < 0.0001). EVH had fewer complications (NS), and postoperative pain was significantly less (p = 0.0034). The major advantages of endoscopic vein harvesting are a significant reduction of postoperative pain and strikingly better cosmetic results. Wound complications seem to be less frequent.

Prevalence of iodine inadequacy in Switzerland assessed by the estimated average requirement cut-point method in relation to the impact of iodized salt.

OBJECTIVE: To assess the iodine status of Swiss population groups and to evaluate the influence of iodized salt as a vector for iodine fortification. DESIGN: The relationship between 24 h urinary iodine and Na excretions was assessed in the general population after correcting for confounders. Single-day intakes were estimated assuming that 92 % of dietary iodine was excreted in 24 h urine. Usual intake distributions were derived for male and female population groups after adjustment for within-subject variability. The estimated average requirement (EAR) cut-point method was applied as guidance to assess the inadequacy of the iodine supply. SETTING: Public health strategies to reduce the dietary salt intake in the general population may affect its iodine supply. SUBJECTS: The study population (1481 volunteers, aged ≥15 years) was randomly selected from three different linguistic regions of Switzerland. RESULTS: The 24 h urine samples from 1420 participants were determined to be properly collected. Mean iodine intakes obtained for men (n 705) and women (n 715) were 179 (sd 68.1) µg/d and 138 (sd 57.8) µg/d, respectively. Urinary Na and Ca, and BMI were significantly and positively associated with higher iodine intake, as were men and non-smokers. Fifty-four per cent of the total iodine intake originated from iodized salt. The prevalence of inadequate iodine intake as estimated by the EAR cut-point method was 2 % for men and 14 % for women. CONCLUSIONS: The estimated prevalence of inadequate iodine intake was within the optimal target range of 2-3 % for men, but not for women.

Changes of Root Length and Root-to-Crown Ratio after Apical Surgery: An Analysis by Using Cone-beam Computed Tomography.

INTRODUCTION: Apical surgery is an important treatment option for teeth with post-treatment periodontitis. Although apical surgery involves root-end resection, no morphometric data are yet available about root-end resection and its impact on the root-to-crown ratio (RCR). The present study assessed the length of apicectomy and calculated the loss of root length and changes of RCR after apical surgery. METHODS: In a prospective clinical study, cone-beam computed tomography scans were taken preoperatively and postoperatively. From these images, the crown and root lengths of 61 roots (54 teeth in 47 patients) were measured before and after apical surgery. Data were collected relative to the cementoenamel junction (CEJ) as well as to the crestal bone level (CBL). One observer took all measurements twice (to calculate the intraobserver variability), and the means were used for further analysis. The following parameters were assessed for all treated teeth as well as for specific tooth groups: length of root-end resection and percentage change of root length, preoperative and postoperative RCRs, and percentage change of RCR after apical surgery. RESULTS: The mean length of root-end resection was 3.58 ± 1.43 mm (relative to the CBL). This amounted to a loss of 33.2% of clinical and 26% of anatomic root length. There was an overall significant difference between the tooth groups (P < .05). There was also a statistically significant difference comparing mandibular and maxillary teeth (P < .05), but not for incisors/canines versus premolars/molars (P = .125). The mean preoperative and postoperative RCRs (relative to CEJ) were 1.83 and 1.35, respectively (P < .001). With regard to the CBL reference, the mean preoperative and postoperative RCRs were 1.08 and 0.71 (CBL), respectively (P < .001). The calculated changes of RCR after apical surgery were 24.8% relative to CEJ and 33.3% relative to CBL (P < .001). Across the different tooth groups, the mean RCR was not significantly different (P = .244 for CEJ and 0.114 for CBL). CONCLUSIONS: This CBCT-based study demonstrated that the RCR is significantly changed after root-end resection in apical surgery irrespective of the clinical (CBL) or anatomic (CEJ) reference levels. The lowest, and thus clinically most critical, postoperative RCR was observed in maxillary incisors. Future clinical studies need to show the impact of resection length and RCR changes on the outcome of apical surgery.

Accessory phases as a tool to investigate magmatic underplating in polymetamorphic metasediments : an example from a fossil lower crust : Ivrea Verbano zne, NW Italy

The Ivrea and the Strona-Ceneri zones, NW italy and S Switzerland, offer the possibility to study the continental crust of the Southern Alps. Because of its high metamorphic degree and the abundant Permo- Carboniferous mafic intrusions, the Ivrea Zone is classically interpreted an exposed section trough the Permian lower crust. The present work is focused here on metasedimentary slices (septa) intercalated within Permian gabbro (mafic complex). In particular I studied the evolution of accessory phases such as rutile and zircon and the chemistry of the metasediments. The septa build an irregular and discontinuous band that cut obliquely the mafic complex from its deepest part (N) to its roof (S). The chemistry of the metasediments evolves along the band and the chemical evolution can be compared with that observed in the country-rock surrounding the mafic intrusion to the NE and overprinted by a main regional metamorphic event. This suggests that the degree of chemical depletion of the septa was mainly established during the same regional metamorphic event. Moreover it suggests that incorporation of the septa within the gabbro did not modify their original stratigraphie distribution within the crust. It implies that the mafic complex has been emplaced following a dynamic substantially different from the classic model of « gabbro glacier » (Quick et al., 1992; Quick et al., 1994). It is more likely that it has been emplaced by repeated injections of sills at different depths during a protracted period of time. Zircon trace elements and U-Pb ages suggest that regional metamorphism occurred 330-320Ma, the first sills in the deepest part of the Mafic Complex are injected at ~300Ma, the mafic magmas reached higher levels in the crust at 285Ma and the magmatic activity continued locally until 275Ma. The ages of detrital cores in zircons fix the maximal sedimentation age at ~370Ma, this age corresponds therefore with the maximal age of the incorporation of the Ivrea zone within the lower crust. I propose that the Ivrea zone has been accreted to the lower crust during the Hercynian orogeny sensu lato. The analysis of detrital ages suggests that the source terrains for the Ivrea zone and those for the Strona-Ceneri zone have a completely different Palaeozoic history. The systematic analysis of rutile in partially molten metasediments of the Ivrea zone reveals the occurrence of two generations. The two generations are characterized by a different chemistry and textural distribution. A first generation is formed during pro-grade metamorphism in the restitic counterpart. The second generation is formed in the melts during cooling at the same time that part of the first generation re-equilibrate. Re-equilibration of the first generation seems to be spatially controlled by the presence of fluids. Locally the second generation forms overgrowths on the first generation. Considered the different diffusivity of U and Pb in rutile, U heterogeneities have important implication for U-Pb dating of rutile. ID-TIMS and LA-ICPMS dating coupled with a careful textural investigation (SEM) suggest that rutile grains are characterized by multiple path along which Pb diffusion can occur: volume diffusion is an important process, but intragrain and subgrain boundaries provide additional high diffusivity pathways for Pb escape and reduce drastically the effective diffusion length. -- La zone d'Ivrea et la zone de Strona-Ceneri, en Italie nord-occidentale et Suisse méridionale, offrent la possibilité d'étudier la croûte continentale des Alpes du Sud. En raison du haut degré métamorphique et l'abondance d'intrusions mafiques d'âge Permo-Carbonifère [complexe mafique), la zone d'Ivrea est interprétée classiquement comme de la croûte inférieure permienne. Ce travail ce concentre sur des bandes metasédimentaires (septa) incorporées dans les magmas mafiques lors de l'intrusion. Les septa forment une bande irrégulière qui coupe obliquement le complexe mafique du bas (N) vers le haut (S). La chimie des septa évolue du bas vers le haut et l'évolution chimique se rapproche de l'évolution observé dans la roche encaissante l'intrusion affecté par un événement métamorphique régionale. Cette relation suggère que le degré d'appauvrissement chimique des septa a été établit principalement lors de l'événement métamorphique régional. De plus l'incorporation dans les gabbros n'a pas perturbée la distribution stratigraphique originelle des septa. Ces deux observations impliquent que le métamorphisme dans la roche encaissante précède la mise en place du gabbro et que cette dernière ne se fait pas selon le modèle classique (« gabbro glacier » de Quick et al., 1992, 1994), mais se fait plutôt par injections répétées de sills a différentes profondeurs. Les âges U-Pb et les éléments traces des zircons suggèrent que le métamorphisme régionale a eu lieu 330-320Ma, alors que les premiers sills dans la partie profonde du Mafic Complex s'injectent à ~300Ma, le magmatisme mafique atteigne des niveaux supérieurs à 285Ma et continue localement jusqu'à 270Ma. Les âges des coeurs détritiques des zircons permettent de fixer l'âge maximale de sédimentation à ~370Ma ce qui correspond donc à l'âge maximale de l'incorporation de la zone d'Ivrea dans la croûte inférieur. L'analyse systématique des rutiles, nous a permit de montrer l'existence de plusieurs générations qui ont une répartition texturale et une chimie différente. Une génération se forme lors de l'événement UHT dans les restites, une autre génération se forme dans les liquides lors du refroidissement, au même temps qu'une partie de la première génération se rééquilibre au niveau du Zr. Localement la deuxième génération peut former des surcroissances autour de la première génération. Dans ces cas, des fortes différences en uranium entre les deux générations ont des importantes implications pour la datation U-Pb sur rutile. Classiquement les ratios Pb/U dans le rutile sont interprétés comme indiquant l'âges du refroidissement du minéral sous une température à la quelle la diffusion du Pb dans le minéral n'est plus détectable et la diffusion à plus hautes températures est assumée se faire par «volume diffusion» dans le grain (Mezger et al., 1989). Par des datations ID-TIMS (sur grain entier) et LA-ICPMS (in-situ) et une analyse texturale (MEB) approfondie nous montrons que cette supposition est trop simpliste et que le rutile est repartie en sous-domaines. Chacun de ces domaines a ça propre longueur ou chemin de diffusion spécifique. Nous proposons donc une nouvelle approche plus cohérente pour l'interprétation des âges U-Pb sur rutile.

Melanoma patients respond to a cytotoxic T lymphocyte-defined self-peptide with diverse and nonoverlapping T-cell receptor repertoires.

HLA-A2+ melanoma patients develop naturally a strong CD8+ T cell response to a self-peptide derived from Melan-A. Here, we have used HLA-A2/peptide tetramers to isolate Melan-A-specific T cells from tumor-infiltrated lymph nodes of two HLA-A2+ melanoma patients and analyzed their TCR beta chain V segment and complementarity determining region 3 length and sequence. We found a broad diversity in Melan-A-specific immune T-cell receptor (TCR) repertoires in terms of both TCR beta chain variable gene segment usage and clonal composition. In addition, immune TCR repertoires selected in the patients were not overlapping. In contrast to previously characterized CD8+ T-cell responses to viral infections, this study provides evidence against usage of highly restricted TCR repertoire in the natural response to a self-differentiation tumor antigen.