Assessment of occlusive arterial disease of abdominal aorta and lower extremities arteries : value of multidetector CT angiography using and adaptative acquisition method

Rapport de synthèse : Objectif : Le but de ce travail est d`étudier l'angiographie par scanner multi-barrette (AS) dans l'évaluation de l'artériopathie oblitérante (AOMI) de l'aorte abdominale et des membres inférieurs utilisant une méthode adaptative d'acquisition pour optimiser le rehaussement artériel en particulier pour le lit artériel distal et les artères des pieds. Matériels et méthodes : Trente-quatre patients pressentant une AOMI ont bénéficié d'une angiographie trans-cathéter (ATC) et d'une AS dans un délai inférieur ou égal à 15 jours. L'AS a été effectuée du tronc coeliaque jusqu'aux artères des pieds en une seule acquisition utilisant une haute résolution spatiale (16x0.625 mm). La vitesse de table et le temps de rotation pour chaque examen ont été choisis selon le temps de transit du produit de contraste, obtenu après un bolus test. Une quantité totale de 130 ml de contraste à 4 ml/s a été utilisée. L'analyse des images de l'AS a été effectuée par deux observateurs et les données ATC ont été interprétées de manière indépendante par deux autres observateurs. L'analyse a inclus la qualité de l'image et la détection de sténose supérieure ou égale à 50 % par patient et par segment artériel. La sensibilité et la spécificité de l'AS ont été calculées en considérant l'ATC comme examen de référence. La variabilité Interobservateur a été mesurée au moyen d'une statistique de kappa. Résultas : L'ATC a été non-conclusive dans 0.7 % des segments, tandis que l'AS était conclusive dans tous les segments. Sur l'analyse par patient, la sensibilité et la spécificité totales pour détecter une sténose significative égale ou supérieure à 50 % étaient de 100 %. L'analyse par segment a montré des sensibilités et de spécificités variant respectivement de 91 à 100 % et de 81 à 100 %. L'analyse des artères distales des pieds a révélé une sensibilité de 100 % et une spécificité de 90 %. Conclusion : L'angiographie par CT multi-barrettes utilisant cette méthode adaptative d'acquisition améliore la qualité de l'image et fournit une technique non-invasive et fiable pour évaluer L'AOMI, y compris les artères distales des pieds.

The efficiency of antigen recognition by CD8+ CTL clones is determined by the frequency of serial TCR engagement.

Using H-2Kd-restricted CTL clones, which are specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS(252-260) (SYIPSAEKI) and permit assessment of TCR-ligand interactions by TCR photoaffinity labeling, we have previously identified several peptide derivative variants for which TCR-ligand binding and the efficiency of Ag recognition deviated by fivefold or more. Here we report that the functional CTL response (cytotoxicity and IFN-gamma production) correlated with the rate of TCR-ligand complex dissociation, but not the avidity of TCR-ligand binding. While peptide antagonists exhibited very rapid TCR-ligand complex dissociation, slightly slower dissociation was observed for strong agonists. Conversely and surprisingly, weak agonists typically displayed slower dissociation than the wild-type agonists. Acceleration of TCR-ligand complex dissociation by blocking CD8 participation in TCR-ligand binding increased the efficiency of Ag recognition in cases where dissociation was slow. In addition, permanent TCR engagement by TCR-ligand photocross-linking completely abolished sustained intracellular calcium mobilization, which is required for T cell activation. These results indicate that the functional CTL response depends on the frequency of serial TCR engagement, which, in turn, is determined by the rate of TCR-ligand complex dissociation.

Inter-informant agreement and prevalence estimates for mood syndromes: Direct interview vs. family history method.

BACKGROUND: The use of the family history method is recommended in family studies as a type of proxy interview of non-participating relatives. However, using different sources of information can result in bias as direct interviews may provide a higher likelihood of assigning diagnoses than family history reports. The aims of the present study were to: 1) compare diagnoses for threshold and subthreshold mood syndromes from interviews to those relying on information from relatives; 2) test the appropriateness of lowering the diagnostic threshold and combining multiple reports from the family history method to obtain comparable prevalence estimates to the interviews; 3) identify factors that influence the likelihood of agreement and reporting of disorders by informants. METHODS: Within a family study, 1621 informant-index subject pairs were identified. DSM-5 diagnoses from direct interviews of index subjects were compared to those derived from family history information provided by their first-degree relatives. RESULTS: 1) Inter-informant agreement was acceptable for Mania, but low for all other mood syndromes. 2) Except for Mania and subthreshold depression, the family history method provided significantly lower prevalence estimates. The gap improved for all other syndromes after lowering the threshold of the family history method. 3) Individuals who had a history of depression themselves were more likely to report depression in their relatives. LIMITATIONS: Low proportion of affected individuals for manic syndromes and lack of independence of data. CONCLUSIONS: The higher likelihood of reporting disorders by affected informants entails the risk of overestimation of the size of familial aggregation of depression.

Quantifying ChIP-seq data: a spiking method providing an internal reference for sample-to-sample normalization.

Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) experiments are widely used to determine, within entire genomes, the occupancy sites of any protein of interest, including, for example, transcription factors, RNA polymerases, or histones with or without various modifications. In addition to allowing the determination of occupancy sites within one cell type and under one condition, this method allows, in principle, the establishment and comparison of occupancy maps in various cell types, tissues, and conditions. Such comparisons require, however, that samples be normalized. Widely used normalization methods that include a quantile normalization step perform well when factor occupancy varies at a subset of sites, but may miss uniform genome-wide increases or decreases in site occupancy. We describe a spike adjustment procedure (SAP) that, unlike commonly used normalization methods intervening at the analysis stage, entails an experimental step prior to immunoprecipitation. A constant, low amount from a single batch of chromatin of a foreign genome is added to the experimental chromatin. This "spike" chromatin then serves as an internal control to which the experimental signals can be adjusted. We show that the method improves similarity between replicates and reveals biological differences including global and largely uniform changes.

A novel method for automated classification of epileptiform activity in the human electroencephalogram-based on independent component analysis.

Diagnosis of several neurological disorders is based on the detection of typical pathological patterns in the electroencephalogram (EEG). This is a time-consuming task requiring significant training and experience. Automatic detection of these EEG patterns would greatly assist in quantitative analysis and interpretation. We present a method, which allows automatic detection of epileptiform events and discrimination of them from eye blinks, and is based on features derived using a novel application of independent component analysis. The algorithm was trained and cross validated using seven EEGs with epileptiform activity. For epileptiform events with compensation for eyeblinks, the sensitivity was 65 +/- 22% at a specificity of 86 +/- 7% (mean +/- SD). With feature extraction by PCA or classification of raw data, specificity reduced to 76 and 74%, respectively, for the same sensitivity. On exactly the same data, the commercially available software Reveal had a maximum sensitivity of 30% and concurrent specificity of 77%. Our algorithm performed well at detecting epileptiform events in this preliminary test and offers a flexible tool that is intended to be generalized to the simultaneous classification of many waveforms in the EEG.

Development of a cost-effective method for platelet-rich plasma (PRP) preparation for topical wound healing.

Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood having platelet concentrations above baseline whole-blood values due to processing and concentration. PRP is used in various surgical fields to enhance soft-tissue and bone healing by delivering supra-physiological concentrations of autologous platelets at the site of tissue damage. These preparations may provide a good cellular source of various growth factors and cytokines, and modulate tissue response to injury. Common clinically available materials for blood preparations combined with a two-step centrifugation protocol at 280g each, to ensure cellular component integrity, provided platelet preparations which were concentrated 2-3 fold over total blood values. Costs were shown to be lower than those of other methods which require specific equipment and high-cost disposables, while safety and traceability can be increased. PRP can be used for the treatment of wounds of all types including burns and also of split-thickness skin graft donor sites, which are frequently used in burn management. The procedure can be standardized and is easy to adapt in clinical settings with minimal infrastructure, thus enabling large numbers of patients to benefit from a form of cellular therapy.

Spatial relationship between the atmospheric circulation and the precipitation measured in the western Swiss Alps by means of the analogue method

An adaptation technique based on the synoptic atmospheric circulation to forecast local precipitation, namely the analogue method, has been implemented for the western Swiss Alps. During the calibration procedure, relevance maps were established for the geopotential height data. These maps highlight the locations were the synoptic circulation was found of interest for the precipitation forecasting at two rain gauge stations (Binn and Les Marécottes) that are located both in the alpine Rhône catchment, at a distance of about 100 km from each other. These two stations are sensitive to different atmospheric circulations. We have observed that the most relevant data for the analogue method can be found where specific atmospheric circulation patterns appear concomitantly with heavy precipitation events. Those skilled regions are coherent with the atmospheric flows illustrated, for example, by means of the back trajectories of air masses. Indeed, the circulation recurrently diverges from the climatology during days with strong precipitation on the southern part of the alpine Rhône catchment. We have found that for over 152 days with precipitation amount above 50 mm at the Binn station, only 3 did not show a trajectory of a southerly flow, meaning that such a circulation was present for 98% of the events. Time evolution of the relevance maps confirms that the atmospheric circulation variables have significantly better forecasting skills close to the precipitation period, and that it seems pointless for the analogue method to consider circulation information days before a precipitation event as a primary predictor. Even though the occurrence of some critical circulation patterns leading to heavy precipitation events can be detected by precursors at remote locations and 1 week ahead (Grazzini, 2007; Martius et al., 2008), time extrapolation by the analogue method seems to be rather poor. This would suggest, in accordance with previous studies (Obled et al., 2002; Bontron and Obled, 2005), that time extrapolation should be done by the Global Circulation Model, which can process atmospheric variables that can be used by the adaptation method.

Combined laparoscopic-endoscopic method using an omental plug for therapy of gastroduodenal ulcer perforation.

BACKGROUND: Laparoscopic techniques have been proposed as an alternative to open surgery for therapy of peptic ulcer perforation. They provide better postoperative comfort and absence of parietal complications, but leakage occurs in 5% of cases. We describe a new method combining laparoscopy and endoluminal endoscopy, designed to ensure complete closure of the perforation. METHODS: Six patients with anterior ulcer perforations (4 duodenal, 2 gastric) underwent a concomitant laparoscopy and endoluminal endoscopy with closure of the orifice by an omental plug attracted into the digestive tract. RESULTS: All perforations were sealed. The mean operating time was 72 minutes. The mean hospital stay was 5.5 days. There was no morbidity and no mortality. At the 30-day evaluation all ulcers but one (due to Helicobacter pylori persistence) were healed. CONCLUSIONS: This method is safe and effective. Its advantages compared with open surgery or laparoscopic patching as well as its cost-effectiveness should be studied in prospective randomized trials.

Response-to-comments about: "Is it really the method for carbon dioxide determination in human postmortem cardiac gas samples using Headspace-Gas Chromatography-Mass Spectrometry valid?" from T. Saffaj and B. Ihssane

Saffaj et al. recently criticized our method of monitoring carbon dioxide in human postmortem cardiac gas samples using Headspace-Gas Chromatography-Mass Spectrometry. According to the authors, their demonstration, based on the latest SFSTP guidelines (established after 2007 [1,2]) fitted for the validation of drug monitoring bioanalytical methods, has put in evidence potential errors. However, our validation approach was built using SFSTP guidelines established before 2007 [3-6]. We justify the use of these guidelines because of the post-mortem context of the study (and not clinical) and the gaseous state of the sample (and not solid or liquid). Using these guidelines, our validation remains correct.

Using a Bayesian method to assign individuals to karyotypic taxa in shrew hybrid zones.

Individuals sampled in hybrid zones are usually analysed according to their sampling locality, morphology, behaviour or karyotype. But the increasing availability of genetic information more and more favours its use for individual sorting purposes and numerous assignment methods based on the genetic composition of individuals have been developed. The shrews of the Sorex araneus group offer good opportunities to test the genetic assignment on individuals identified by their karyotype. Here we explored the potential and efficiency of a Bayesian assignment method combined or not with a reference dataset to study admixture and individual assignment in the difficult context of two hybrid zones between karyotypic species of the Sorex araneus group. As a whole, we assigned more than 80% of the individuals to their respective karyotypic categories (i.e. 'pure' species or hybrids). This assignment level is comparable to what was obtained for the same species away from hybrid zones. Additionally, we showed that the assignment result for several individuals was strongly affected by the inclusion or not of a reference dataset. This highlights the importance of such comparisons when analysing hybrid zones. Finally, differences between the admixture levels detected in both hybrid zones support the hypothesis of an impact of chromosomal rearrangements on gene flow.

Prognostic value of serial blood S100B determinations in stage IIB-III melanoma patients: a corollary study to EORTC trial 18952.

S100B is a prognostic factor for melanoma as elevated levels correlate with disease progression and poor outcome. We determined its prognostic value based on updated information using serial determinations in stage IIb/III melanoma patients. 211 Patients who participated in the EORTC 18952 trial, evaluating efficacy of adjuvant intermediate doses of interferon α2b (IFN) versus observation, entered a corollary study. Over a period of 36 months, 918 serum samples were collected. The Cox time-dependent model was used to assess prognostic value of the latest (most recent) S100B determination. At first measurement, 178 patients had S100B values <0.2 μg/l and 33 ≥ 0.2 μg/l. Within the first group, 61 patients had, later on, an increased value of S100B (≥ 0.2 μg/l). An initial increased value of S100B, or during follow-up, was associated with worse distant metastasis-free survival (DMFS); hazard ratio (HR) of S100B ≥ 0.2 versus S100B < 0.2 was 5.57 (95% confidence interval (CI) 3.81-8.16), P < 0.0001, after adjustment for stage, number of lymph nodes and sex. In stage IIb patients, the HR adjusted for sex was 2.14 (95% CI 0.71, 6.42), whereas in stage III, the HR adjusted for stage, number of lymph nodes and sex was 6.76 (95% CI 4.50-10.16). Similar results were observed regarding overall survival (OS). Serial determination of S100B in stage IIb-III melanoma is a strong independent prognostic marker, even stronger compared to stage and number of positive lymph nodes. The prognostic impact of S100B ≥ 0.2 μg/l is more pronounced in stage III disease compared with stage IIb.

BRAF mutation in 'sarcomas': a possible method to detect de-differentiated melanomas

AIMS: BRAF is mutated in 50-60% of melanomas, but BRAF mutation in sarcomas has not been systematically evaluated. Some melanomas are spindled and may show no immunohistochemical evidence of melanocytic differentiation. Similarly, many sarcomas are undifferentiated, i.e. undifferentiated pleomorphic sarcomas (UPS). Diagnosing melanoma versus sarcoma in an undifferentiated spindle cell malignancy can be challenging. Our aim was to evaluate the prevalence of BRAF mutation in sarcomas and the use of BRAF mutational status in the diagnosis of spindle cell malignancies. METHODS AND RESULTS: BRAF mutational analysis was performed on tissue from 104 patients: 90 with sarcoma only (50 UPS) and 14 with sarcoma and melanoma (seven UPS). In the sarcoma-only group, BRAF mutation was absent. In the sarcoma-melanoma group, three sarcomas showed BRAF mutation; all were UPS, occurred after the melanomas and did not stain for melanocytic markers. One melanoma-sarcoma pair showed identical BRAF V600E mutations. CONCLUSIONS: The presence of BRAF mutation in these tumours raises the possibility that poorly differentiated spindle cell malignancies with BRAF mutation may represent melanomas, and BRAF mutational analysis should be considered in a patient with a spindle cell malignancy and a history of melanoma, as a positive result may indicate de-differentiated melanoma.