Automatic wheeze detection based on auditory modelling

Automatic wheeze detection has several potential benefits compared with reliance on human auscultation: it is experience independent, an automated historical record can easily be kept, and it allows quantification of wheeze severity. Previous attempts to detect wheezes automatically have had partial success but have not been reliable enough to become widely accepted as a useful tool. In this paper an improved algorithm for automatic wheeze detection based on auditory modelling is developed, called the frequency- and duration-dependent threshold algorithm. The mean frequency and duration of each wheeze component are obtained automatically. The detected wheezes are marked on a spectrogram. In the new algorithm, the concept of a frequency- and duration-dependent threshold for wheeze detection is introduced. Another departure from previous work is that the threshold is based not on global power but on power corresponding to a particular frequency range. The algorithm has been tested on 36 subjects, 11 of whom exhibited characteristics of wheeze. The results show a marked improvement in the accuracy of wheeze detection when compared with previous algorithms

Genetics of Amyotrophic Lateral Sclerosis

La sclérose latérale amyotrophique (SLA) est la maladie des neurones moteurs la plus fréquente, affectant 4-6 individus par 100,000 habitants à l’échelle mondiale. La maladie se caractérise par une faiblesse et une atrophie musculaire suite à la dégénérescence des neurones du cortex moteur, tronc cérébral et moelle épinière. Les personnes atteintes développent les premiers symptômes à l’âge adulte et la maladie progresse sur une période de trois à cinq ans. Il a été répertorié qu’environ 10% des patients ont une histoire familiale de SLA; 90% des gens affectés le sont donc de façon sporadique. La découverte il y a 19 ans de mutations dans le gène zinc/copper superoxide dismutase (SOD1), présentes dans 15-20% des cas familiaux de SLA et environ 2% du total des individus affectés, a été l’événement déclencheur pour la découverte de variations génétiques responsables de la maladie. La recherche sur la génétique de la SLA a connu une progression rapide ces quatre dernières années avec l’identification de mutations dans de nouveaux gènes. Toutefois, même si certains de ces gènes ont été démontrés comme réellement liés à la maladie, la contribution d’autres gènes demeure incertaine puisque les résultats publiés de ceux-ci n’ont pas, à ce jour, été répliqués. Une portion substantielle de cas reste cependant à être génétiquement expliquée, et aucun traitement à ce jour n’a été démontré comme étant efficace pour remédier, atténuer ou prévenir la maladie. Le but du projet de recherche de doctorat était d’identifier de nouveaux gènes mutés dans la SLA, tout en évaluant la contribution de gènes nouvellement identifiés chez une importante cohorte multiethnique de cas familiaux et sporadiques. Les résultats présentés sont organisés en trois sections différentes. Dans un premier temps, la contribution de mutations présentes dans le gène FUS est évaluée chez les patients familiaux, sporadiques et juvéniles de SLA. Précisément, de nouvelles mutations sont rapportées et la proportion de mutations retrouvées chez les cas familiaux et sporadiques de SLA est évaluée. De plus, une nouvelle mutation est rapportée dans un cas juvénile de SLA; cette étude de cas est discutée. Dans un deuxième temps, de nouvelles avenues génétiques sont explorées concernant le gène SOD1. En effet, une nouvelle mutation complexe est rapportée chez une famille française de SLA. De plus, la possibilité qu’une mutation présente dans un autre gène impliqué dans la SLA ait un impact sur l’épissage du gène SOD1 est évaluée. Finalement, la dernière section explique la contribution de nouveaux gènes candidats chez les patients atteints de SLA. Spécifiquement, le rôle des gènes OPTN, SIGMAR1 et SORT1 dans le phénotype de SLA est évalué. Il est souhaité que nos résultats combinés avec les récents développements en génétique et biologie moléculaire permettent une meilleure compréhension du mécanisme pathologique responsable de cette terrible maladie tout en guidant le déploiement de thérapies suite à l’identification des cibles appropriées.Amyotrophic lateral sclerosis (ALS) is the most common of motor neuron diseases, affecting 4-6 individuals per 100,000 individuals worldwide. ALS is characterized by muscle weakness and atrophy caused by the degeneration of neurons located in the motor cortex, brain stem and spinal cord. This fatal disease generally has an adult onset and progresses over a three to five year period. While 10% of patients affected have a family history of the disease, 90% of cases do not and are considered sporadic. The finding of mutations in the zinc/copper superoxide dismutase gene (SOD1) gene 19 years ago in about 15-20% of familial ALS (FALS) patients and approximately 2% of overall cases developed the interest of identifying rare genetics variants causing the disease. The ALS research field experienced a rapid progression during the last four years as mutations in new genes have been identified. While mutations in some of those new genes have been clearly linked to ALS, the role of others is still questionable and so far has not been positively replicated in other populations. Importantly, a significant portion of cases still need to be genetically explained and, unfortunately, there is still no effective treatment to cure, attenuate or prevent the disease. The aim of this Ph.D research project was to identify new ALS mutated genes while analysing the causative role of other newly identified genes in a large familial and sporadic ALS cohort of different origins. The results presented here are categorized into three different sections. First, the contribution of FUS mutations to familial, sporadic and juvenile ALS is analysed. Specifically, new FUS mutations are reported in ALS cases and the proportions of variants present in the tested familial and sporadic ALS cohorts are assessed. In addition, a new mutation is reported in a juvenile ALS patient, and this interesting case is discussed. Second, new genetic avenues are explored for the SOD1 gene. Precisely, a new and complex SOD1 mutation is reported in a French ALS family. Moreover, the possibility that other ALS mutated genes influence SOD1 splicing events is evaluated. Third, the contribution of new candidate genes is evaluated. Precisely, the contribution of OPTN, SIGMAR1 and SORT1 genes to the ALS phenotype is assessed. Hopefully, our different findings combined with recent developments in genetics and molecular biology will permit a better understanding of the pathological mechanisms involved in the disease and will lead to the identification of the right targets in order to develop appropriate therapeutics for ALS patients

Chapter Genetics of Amyotrophic Lateral Sclerosis

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Comparative interactomics analysis of different ALS-associated proteins identifies converging molecular pathways

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment available. An increasing number of genetic causes of ALS are being identified, but how these genetic defects lead to motor neuron degeneration and to which extent they affect common cellular pathways remains incompletely understood. To address these questions, we performed an interactomic analysis to identify binding partners of wild-type (WT) and ALS-associated mutant versions of ATXN2, C9orf72, FUS, OPTN, TDP-43 and UBQLN2 in neuronal cells. This analysis identified several known but also many novel binding partners of these proteins

Discrimination of intravascular lumen and dissections in single intravascular ultrasound images using subtraction, conventional averaging and saline flush

With current 30-MHz intravascular ultrasound systems, flowing blood may cause considerable backscatter which in real-time images is characterized by dynamic speckle. However, in a single intravascular ultrasound image (still-frame) the discrimination between arterial lumen and wall may be difficult due to the frozen intraluminal speckle, particularly in the presence of dissections. We compared subtraction, averaging and saline flush as methods to improve the discrimination between arterial lumen and wall in a single image. The real-time images served as gold standard. In 22 patients who underwent peripheral balloon angioplasty, ultrasound images obtained from 84 sites were examined. The sensitivity and specificity of detecting dissections were in the subtraction image 85% and 100%, in the averaged image 57% and 96%, and in the saline flush image 58% and 86%, respectively. Subtraction is a promising method to outline the irregular lumen in a single image

Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox

AbstractObjective. To relate local arterial geometry with markers that are thought to be related to plaque rupture.Background. Plaque rupture often occurs at sites with minor luminal stenosis and has retrospectively been characterized by colocalization of inflammatory cells. Recent studies have demonstrated that luminal narrowing is related with the mode of atherosclerotic arterial remodeling.Methods. We obtained 1,521 cross section slices at regular intervals from 50 atherosclerotic femoral arteries. Per artery, the slices with the largest and smallest lumen area, vessel area and plaque area were selected for staining on the presence of macrophages (CD68), T-lymphocytes (CD45RO), smooth muscle cells (alpha-actin) and collagen.Results. Inflammation of the cap or shoulder of the plaque was observed in 33% of all cross sections. Significantly more CD68 and CD45RO positive cells, more atheroma, less collagen and less alpha-actin positive staining was observed in cross sections with the largest plaque area and largest vessel area vs. cross sections with the smallest plaque area and smallest vessel area, respectively. No difference in the number of inflammatory cells was observed between cross sections with the largest and smallest lumen area.Conclusion. Intraindividually, pathohistologic markers previously reported to be related to plaque vulnerability were associated with a larger plaque area and vessel area. In addition, inflammation of the cap and shoulder of the plaque was a common finding in the atherosclerotic femoral artery

T eleauscu ltation: Bringing you to the bedside

A custom-made device was used for the acquisition, dig iti1ation. compression. storage and telephone transmiss ion o f respiratory sounds anJ airflow data. Acoustical infomrntion from two patie nts at a small community in rural Mani toba was sent over a distance of 500 km vi a conventional telephone lines . D ig ital transmission left the resp iratory sounds unaffected by telephone line noise. Data processing by computer at the rece ivi ng s ite provided more de tail than would have been avail able o n conventional auscul tati on . This new method fo r tcleauseultation could he of value not only in remote areas but also for the survei I lance of patients at home in urban setting s

Intravascular ultrasound predictors of outcome after peripheral balloon angioplasty

Objective:This study investigates the potential role of intravascular ultrasound (IVUS) in the outcome in patients undergoing percutaneous transluminal angioplasty (PTA) of the superficial femoral artery.Materials:Angiographic and the qualitative and quantitative IVUS data obtained at the narrowest site derived from 39 patients before and after PTA were analysed.Results:Angiographically the diameter of the remaining stenosis seen after PTA was classified as < 50% in 31 patients (success); in eight patients a failure was encountered. Evaluating at 6 months the functional and anatomic results of the PTA in 31 patients, the intervention was a success in 14 patients (Group I) and a failure in 17 patients (Group II). The remaining eight patients defined as angiographic failure following PTA comprised Group III. Neither qualitative nor quantitative IVUS data obtained before PTA could predict outcome. Conversely, after PTA, the extent of dissection was significantly more severe in Groups II and III than in Group I. Similarly, significant differences were found between Groups I and II for mean free lumen area (13.2 vs. 9.7 mm2, respectively) and mean free lumen diameter (4.1 vs. 3.5 mm, respectively). Quantitative data obtained in Group II were similar to those in Group III.Conclusion:This preliminary study demonstrates that following PTA the extent of dissection, free lumen area and diameter seen with IVUS are predictive factors of patency. Future studies with more patients are mandatory to further highlight the sensitivity of these observations