An overview of nearly a half century of microembolic signal processing techniques

International audienceMicro-emboli detection for patients with high risk of strokes has been performed with transcranial Doppler (TCD) systems since 1969. As a consequence, instrumentation of TCD systems progressed with the introduction of multigate systems, power mode systems and robotized probes, to name but a few. These new types of TCD have increase the chance of robust detections of quite big micro-emboli and at the same time increased the efficiency of artefact rejection.For a couple of years now, it is now possible to prevent cerebrovascular accidents (CVA) by detecting very small micro-emboli, the latter being precursor signs of strokes. For this sake, a new generation of transcranial Doppler (TCD) systems (holter) is used to record examinations of long duration. In an attempt to detect the smallest possible micro-emboli, offline softwares based on recent signal processing techniques complete advantageously these holter systems.In this communication, an overview of fifty years of research developments in embolic signal processing is proposed. What is interesting during this adventure of a half century is that detection methods were inspired as signal processing discoveries coming from speech processing to econometric. With the advent of the artificial intelligence, new challenges are being drawn up

Refroidissement d'un volume fini générant de la chaleur : analyse du processus constructal

International audienceLe problème initial abordé par la théorie constructale envisage l'allocation optimale de matériau hautement conducteur à l'intérieur d'un volume fini générant de la chaleur. L'un des enjeux fondamentaux de la théorie constructale est le déterminisme introduit dans le processus de construction de la solution, bien que de nombreux travaux montrent que cette solution soit non optimale. Après avoir reprécisé les hypothèses physiques utilisées habituellement, cette étude met en exergue certains points analytiques présentant un potentiel d'amélioration vers un optimum. Dans ce cadre, la production de chaleur au sein du matériau hautement conducteur, ainsi que la porosité du volume fini, sont examinées avec une attention particulière

Refroidissement d'un volume fini générant de la chaleur : limites de l'approche constructale

International audienceLa répartition optimale, à l'aide de la théorie constructale, d'un matériau hautement conducteur à l'intérieur d'un volume fini générant de la chaleur est un véritable paradigme. Pourtant, il est difficile de comparer les structures entre-elles du fait du déterminisme de l'approche qui induit des géométries dont les caractéristiques dimensionnelles extérieures diffèrent. Cette étude propose une façon originale de contraindre l'approche constructale au sein d'un volume aux dimensions externes préalablement fixées. Dès lors, cette technique permet de quantifier l'influence de la complexification du réseau de refroidissement sur son efficacité. Les conclusions de l'étude soulignent l'absence de corrélation entre ces deux paramètres

A Signal Processing Method for Artefact Rejection in Transcranial Doppler Signals used for Micro-embolus detection

International audienceArtefacts are High Intensity Transient Signals that appear in the Doppler signal due to probe tapping, probe displacement, patient movement and other external factors during TCD recording. In Holter TCD, the number of artefacts are further increased due to the servo-controlled probe positioning and long recording time. Current artefact rejection methods must be adapted to the new holter devices. Therefore, in this paper we present a complete procedure for eliminating two types of artefacts that occur during Holter TCD. The latter two types are bidirectional areftact, occurring in the energy of both positive and negative frequencies, and unidirectional artefacts occuring only in the energy of the negative frequencies. From a dataset of 25 signals, 218 artefact signatures were identified; 95% of which are bidirectional and 5% unidirectional. As a final result, 98% of the artefacts where successfully removed

A new energy detector of micro-emboli using a time-varying threshold

International audienceDetection of small emboli, precursors of Cerebrovascular Accidents, is a worldwide concern since CVAs represent the second cause of mortality in the world. Computerized analysis of Transcranial Doppler signals can aid early detection of circulating emboli and micro-emboli. Commercially used systems of automatic emboli detection rely on standard short time Fourier transform techniques in which detection is based on constant thresholds. These standard algorithms do not offer robust detections and are incapable of detecting the smallest micro-emboli. To enhance this detection, we propose in this study optimized techniques based on novel methods of threshold application. By implementing our new time-varying threshold of detection, we were able to decrease the probability of non-detection and the probability of false alarm by around half the values obtained by standard techniques. Moreover, our new techniques were clearly efficient in exploiting the transient-like embolic signals and hence make detection of micro-emboli easier and more evident. This was proved by enhancing important parameters of which are the embolus to blood ratio and the peak to threshold ratio. Applied on our set of recorded signals, the new detectors allowed obtaining embolus to blood ratios twice greater than the embolus to blood ratios achieved by standard techniques and a sufficient increase in peak to threshold ratios

A Micro-Embolic Energy Detector based on Sub-band Decomposition

International audienceCerebrovascular Accidents can be caused by cerebral emboli blocking brain blood vessels. Analysis of transcranial Doppler signals practically aids the detection of emboli. Signal processing methods have been proposed for emboli detection. In this study, we introduce a new micro-embolic energy detector composed of N detectors associated to N Doppler frequency sub-bands. To test our detectors, we propose a training phase during which we adjust the optimal number of sub-bands and detection thresholds and a testing phase through which we measure performances. Using real signals, we show that in terms of the number of sub-bands, 4 sub-bands provide the highest detection rate and lowest false alarm. Moreover, compared to standard detectors, the 4 sub-band energy detector reduces the false alarm rate from 44% to 36%, increases the detection rate from 66% to 79% and augments the Embolus to Blood Ratio from 24 dB to 40 dB. This new energy detector permits detecting smallest micro-emboli, precursors of coming large emboli with high stroke risks

Multicenter phase II study of brequinar sodium in patients with advanced lung cancer

A total of 53 patients with advanced lung cancer [non-small-cell (NSC), 21; small-cell (SC), 32] were treated with brequinar sodium. All of the NSC patients were chemotherapy-naive, but 31/32 (97%) SC patients had failed a multiagent chemotherapy program prior to study entry. Brequinar was given intravenously at a median weekly dose of 1200 mg/m 2 . The toxicity was moderate, with 19 patients (36%) experiencing grade 3 or 4 toxicity. Objective responses were observed in one NSC and two SC patients. We conclude that at this dose and on this schedule, brequinar does not have sufficient activity in patients with NSC or in patients with previously treated SC to warrant further evaluation. However, since responses were observed in previously treated SC lung-cancer patients, further evaluation in chemotherapy-naive patients may be warranted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46927/1/280_2004_Article_BF00685878.pd

Capecitabine as Adjuvant Treatment for Stage III Colon Cancer

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Genetic and dietary modulators of the inflammatory response in the gastrointestinal tract of the BXD mouse genetic reference population.

peer reviewedInflammatory gut disorders, including inflammatory bowel disease (IBD), can be impacted by dietary, environmental, and genetic factors. While the incidence of IBD is increasing worldwide, we still lack a complete understanding of the gene-by-environment interactions underlying inflammation and IBD. Here, we profiled the colon transcriptome of 52 BXD mouse strains fed with a chow or high-fat diet (HFD) and identified a subset of BXD strains that exhibit an IBD-like transcriptome signature on HFD, indicating that an interplay of genetics and diet can significantly affect intestinal inflammation. Using gene co-expression analyses, we identified modules that are enriched for IBD-dysregulated genes and found that these IBD-related modules share cis-regulatory elements that are responsive to the STAT2, SMAD3, and REL transcription factors. We used module quantitative trait locus analyses to identify genetic loci associated with the expression of these modules. Through a prioritization scheme involving systems genetics in the mouse and integration with external human datasets, we identified Muc4 and Epha6 as the top candidates mediating differences in HFD-driven intestinal inflammation. This work provides insights into the contribution of genetics and diet to IBD risk and identifies two candidate genes, MUC4 and EPHA6, that may mediate IBD susceptibility in humans

Phase II Study of Biweekly Plitidepsin as Second-Line Therapy for Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium

The objective of this exploratory, open-label, single-arm, phase II clinical trial was to evaluate plitidepsin (5 mg/m2) administered as a 3-hour continuous intravenous infusion every two weeks to patients with locally advanced/metastatic transitional cell carcinoma of the urothelium who relapsed/progressed after first-line chemotherapy. Treatment cycles were repeated for up to 12 cycles or until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. The primary efficacy endpoint was objective response rate according to RECIST. Secondary endpoints were the rate of SD lasting ≥ 6 months and time-to-event variables. Toxicity was assessed using NCI-CTC v. 3.0. Twenty-one patients received 57 treatment cycles. No objective tumor responses occurred. SD lasting <6 months was observed in two of 18 evaluable patients. With a median follow-up of 4.6 months, the median PFR and the median OS were 1.4 months and 2.3 months, respectively. The most common AEs were mild to moderate nausea, fatigue, myalgia and anorexia. Anemia, lymphopenia, and increases in transaminases, alkaline phosphatase and creatinine were the most frequent laboratory abnormalities. No severe neutropenia occurred. Treatment was feasible and generally well tolerated in this patient population; however the lack of antitumor activity precludes further studies of plitidepsin in this setting