Targeting treatment resistant breast cancer stem cells with FKBPL and its peptide derivative, AD-01

FKBPL and its peptide derivative, AD-01, have already demonstrated well-established inhibitory effects on breast cancer growth and CD44 dependent anti-angiogenic activity1, 2, 3. Since breast cancer stem cells (BCSCs) are CD44 positive, we wanted to explore if AD-01 could specifically target BCSCs. FKBPL stable overexpression or AD-01 treatment were highly effective at reducing the BCSC population measured by inhibiting mammosphere forming efficiency (MFE) in cell lines and primary breast cancer samples from both solid breast tumours and pleural effusions. Flow cytometry, to assess the ESA+/CD44+/CD24- subpopulation, validated these results. The ability of AD-01 to inhibit the self-renewal capacity of BCSCs was confirmed across three generations of mammospheres, where mammospheres were completely eradicated by the third generation (p<0.001). Clonogenic assays suggested that AD-01 mediated BCSC differentiation, with a significant decrease in the number of holoclones and an associated increase in meroclones/paraclones. In support of this, the stem cell markers, Nanog and Oct4 were significantly reduced following AD-01 treatment, whilst transfection of FKBPL-targeted siRNAs led to an increase in these markers and in mammosphere forming potential, highlighting the endogenous role of FKBPL in stem cell signalling. The clinical relevance of this was confirmed using a publically available microarray data set (GSE7390), where, high FKBPL and low Nanog expression were independently associated with improved overall survival in breast cancer patients (log rank test p=0.03; hazard ratio=3.01). When AD-01 was combined with other agents, we observed synergistic activity with the Notch inhibitor, DAPT and AD-01 was also able to abrogate a chemo- and radiotherapy induced enrichment in BCSCs. Importantly, using ‘gold standard’ in vivo limiting dilution assays we demonstrated a delay in tumour initiation and reoccurrence in AD-01 treated xenografts. In summary, AD-01 appears to have dual anti-angiogenic and anti-BCSC activity which will be advantageous as this agent enters clinical trial.

Targeting treatment resistant cancer stem cells with FKBPL and its peptide therapeutics

FKBPL and its peptide derivatives have already demonstrated well-established inhibitory effects on cancer growth and CD44-dependent anti-angiogenic activity. Since cancer stem cells (CSCs) are CD44 positive, we wanted to explore if these therapeutics could specifically target CSCs in breast and ovarian cancer. In a tumoursphere assay, FKBPL stable overexpression or FKBPL-based peptide (AD-01, preclinical peptide or ALM201, clinical peptide candidate) treatment were highly effective at reducing the CSC population measured by inhibiting tumoursphere forming efficiency in breast and ovarian cancer cell lines and primary breast cancer samples from both solid breast tumours and pleural effusions. Flow cytometry, to assess the ESA+/CD44+/CD24- and ALDH+ cell subpopulations representative of CSCs, validated these results. The ability of AD-01 and ALM201 to inhibit the self-renewal capacity of CSCs was confirmed across three generations, eradicating CSC completely by the third generation (p<0.001). Furthermore, clonogenic assay demonstrated that FKBPL-based peptides mediated CSC differentiation, with a significant decrease in the number of CSCs or holoclones and an associated increase in differentiated cancer cells or meroclones/paraclones. In addition, AD-01 treatment in vitro and in vivo led to a significant reduction in the stem cell markers, Nanog, Sox2 and Oct4 protein and mRNA levels; whilst transfection of FKBPL-targeted siRNAs led to an increase in these markers and in tumoursphere forming potential, highlighting the endogenous role of FKBPL in stem cell signalling. The clinical relevance of this was confirmed using a publically available microarray data set (GSE7390), where, high FKBPL and low Nanog expression were independently associated with improved overall survival in breast cancer patients (log rank test p=0.03; hazard ratio=3.01). Additionally, when AD-01 was combined with other agents, we observed additive activity with the Notch inhibitor, DAPT and AD-01 was also able to abrogate a chemo- and radiotherapy induced enrichment in CSCs. Importantly, using gold standard in vivo limiting dilution assays we demonstrated a delay in tumour initiation and reoccurrence in AD-01 treated xenografts. In summary, FKBPL-based peptides appear to have dual anti-angiogenic and anti-CSC activity which will be advantageous as this agent enters clinical trial.

Comparison of module detection algorithms in protein networks and investigation of the biological meaning of predicted modules

Background
It is generally acknowledged that a functional understanding of a biological system can only be obtained by an understanding of the collective of molecular interactions in form of biological networks. Protein networks are one particular network type of special importance, because proteins form the functional base units of every biological cell. On a mesoscopic level of protein networks, modules are of significant importance because these building blocks may be the next elementary functional level above individual proteins allowing to gain insight into fundamental organizational principles of biological cells.
Results
In this paper, we provide a comparative analysis of five popular and four novel module detection algorithms. We study these module prediction methods for simulated benchmark networks as well as 10 biological protein interaction networks (PINs). A particular focus of our analysis is placed on the biological meaning of the predicted modules by utilizing the Gene Ontology (GO) database as gold standard for the definition of biological processes. Furthermore, we investigate the robustness of the results by perturbing the PINs simulating in this way our incomplete knowledge of protein networks.
Conclusions
Overall, our study reveals that there is a large heterogeneity among the different module prediction algorithms if one zooms-in the biological level of biological processes in the form of GO terms and all methods are severely affected by a slight perturbation of the networks. However, we also find pathways that are enriched in multiple modules, which could provide important information about the hierarchical organization of the system

Suivi par élastographie ultrasonore après réparation endovasculaire d’anévrisme aorto-iliaque : étude de faisabilité in vivo

Les maladies cardiovasculaires sont la première cause de mortalité dans le monde et les anévrismes de l’aorte abdominale (AAAs) font partie de ce lot déplorable. Un anévrisme est la dilatation d’une artère pouvant conduire à la mort. Une rupture d’AAA s’avère fatale près de 80% du temps. Un moyen de traiter les AAAs est l’insertion d’une endoprothèse (SG) dans l’aorte, communément appelée la réparation endovasculaire (EVAR), afin de réduire la pression exercée par le flux sanguin sur la paroi. L’efficacité de ce traitement est compromise par la survenue d’endofuites (flux sanguins entre la prothèse et le sac anévrismal) pouvant conduire à la rupture de l’anévrisme. Ces flux sanguins peuvent survenir à n’importe quel moment après le traitement EVAR. Une surveillance par tomodensitométrie (CT-scan) annuelle est donc requise, augmentant ainsi le coût du suivi post-EVAR et exposant le patient à la radiation ionisante et aux complications des contrastes iodés. L’endotension est le concept de dilatation de l’anévrisme sans la présence d’une endofuite apparente au CT-scan. Après le traitement EVAR, le sang dans le sac anévrismal coagule pour former un thrombus frais, qui deviendra progressivement un thrombus plus fibreux et plus organisé, donnant lieu à un rétrécissement de l’anévrisme. Il y a très peu de données dans la littérature pour étudier ce processus temporel et la relation entre le thrombus frais et l’endotension. L’étalon d’or du suivi post-EVAR, le CT-scan, ne peut pas détecter la présence de thrombus frais. Il y a donc un besoin d’investir dans une technique sécuritaire et moins coûteuse pour le suivi d’AAAs après EVAR. Une méthode récente, l’élastographie dynamique, mesure l’élasticité des tissus en temps réel. Le principe de cette technique repose sur la génération d’ondes de cisaillement et l’étude de leur propagation afin de remonter aux propriétés mécaniques du milieu étudié. Cette thèse vise l’application de l’élastographie dynamique pour la détection des endofuites ainsi que de la caractérisation mécanique des tissus du sac anévrismal après le traitement EVAR. Ce projet dévoile le potentiel de l’élastographie afin de réduire les dangers de la radiation, de l’utilisation d’agent de contraste ainsi que des coûts du post-EVAR des AAAs. L’élastographie dynamique utilisant le « Shear Wave Imaging » (SWI) est prometteuse. Cette modalité pourrait complémenter l’échographie-Doppler (DUS) déjà utilisée pour le suivi d’examen post-EVAR. Le SWI a le potentiel de fournir des informations sur l’organisation fibreuse du thrombus ainsi que sur la détection d’endofuites. Tout d’abord, le premier objectif de cette thèse consistait à tester le SWI sur des AAAs dans des modèles canins pour la détection d’endofuites et la caractérisation du thrombus. Des SGs furent implantées dans un groupe de 18 chiens avec un anévrisme créé au moyen de la veine jugulaire. 4 anévrismes avaient une endofuite de type I, 13 avaient une endofuite de type II et un anévrisme n’avait pas d’endofuite. Des examens échographiques, DUS et SWI ont été réalisés à l’implantation, puis 1 semaine, 1 mois, 3 mois et 6 mois après le traitement EVAR. Une angiographie, un CT-scan et des coupes macroscopiques ont été produits au sacrifice. Les régions d’endofuites, de thrombus frais et de thrombus organisé furent identifiées et segmentées. Les valeurs de rigidité données par le SWI des différentes régions furent comparées. Celles-ci furent différentes de façon significative (P < 0.001). Également, le SWI a pu détecter la présence d’endofuites où le CT-scan (1) et le DUS (3) ont échoué. Dans la continuité de ces travaux, le deuxième objectif de ce projet fut de caractériser l’évolution du thrombus dans le temps, de même que l’évolution des endofuites après embolisation dans des modèles canins. Dix-huit anévrismes furent créés dans les artères iliaques de neuf modèles canins, suivis d’une endofuite de type I après EVAR. Deux gels embolisants (Chitosan (Chi) ou Chitosan-Sodium-Tetradecyl-Sulfate (Chi-STS)) furent injectés dans le sac anévrismal pour promouvoir la guérison. Des examens échographiques, DUS et SWI ont été effectués à l’implantation et après 1 semaine, 1 mois, 3 mois et 6 mois. Une angiographie, un CT-scan et un examen histologique ont été réalisés au sacrifice afin d’évaluer la présence, le type et la grosseur de l’endofuite. Les valeurs du module d’élasticité des régions d’intérêts ont été identifiées et segmentées sur les données pathologiques. Les régions d’endofuites et de thrombus frais furent différentes de façon significative comparativement aux autres régions (P < 0.001). Les valeurs d’élasticité du thrombus frais à 1 semaine et à 3 mois indiquent que le SWI peut évaluer la maturation du thrombus, de même que caractériser l’évolution et la dégradation des gels embolisants dans le temps. Le SWI a pu détecter des endofuites où le DUS a échoué (2) et, contrairement au CT-scan, détecter la présence de thrombus frais. Finalement, la dernière étape du projet doctoral consistait à appliquer le SWI dans une phase clinique, avec des patients humains ayant déjà un AAA, pour la détection d’endofuite et la caractérisation de l’élasticité des tissus. 25 patients furent sélectionnés pour participer à l’étude. Une comparaison d’imagerie a été produite entre le SWI, le CT-scan et le DUS. Les valeurs de rigidité données par le SWI des différentes régions (endofuite, thrombus) furent identifiées et segmentées. Celles-ci étaient distinctes de façon significative (P < 0.001). Le SWI a détecté 5 endofuites sur 6 (sensibilité de 83.3%) et a eu 6 faux positifs (spécificité de 76%). Le SWI a pu détecter la présence d’endofuites où le CT-scan (2) ainsi que le DUS (2) ont échoué. Il n’y avait pas de différence statistique notable entre la rigidité du thrombus pour un AAA avec endofuite et un AAA sans endofuite. Aucune corrélation n’a pu être établie de façon significative entre les diamètres des AAAs ainsi que leurs variations et l’élasticité du thrombus. Le SWI a le potentiel de détecter les endofuites et caractériser le thrombus selon leurs propriétés mécaniques. Cette technique pourrait être combinée au suivi des AAAs post-EVAR, complémentant ainsi l’imagerie DUS et réduisant le coût et l’exposition à la radiation ionisante et aux agents de contrastes néphrotoxiques.

Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon™ (AmB-D) and two new different AmB formulations. Methods: three products were studied: Fungizon™, and two Fungizon™ /Lipofundin™ admixtures, which were diluted through two methods: in the first one, Fungizon™ was previously diluted with water for injection and then, in Lipofundin™ (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05mg.L-1). Results: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg.L-1, although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. Conclusion: The Fungizon™- Lipofundin™ admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented

Nucleic Acid Diagnostics using Isotachophoresis and Isothermal Amplification

Thesis (Ph.D.)--University of Washington, 2016-08

Effect of insulin resistance on monounsaturated fatty acid levels : a multi-cohort non-targeted metabolomics and mendelian randomization study

Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or β-cell responsiveness (disposition index) during an oral glucose tolerance test. These implicated bile acid, glycerophospholipid and caffeine metabolism for IR and fatty acid biosynthesis for impaired insulin secretion. In MR analysis in two separate cohorts (n = 2,613) followed by replication in three independent studies profiled on different metabolomics platforms (n = 7,824 / 8,961 / 8,330), we discovered and replicated causal effects of IR on lower levels of palmitoleic acid and oleic acid. A trend for a causal effect of IR on higher levels of tyrosine reached significance only in meta-analysis. In one of the largest studies combining "gold standard" measures for insulin responsiveness with non-targeted metabolomics, we found distinct metabolic profiles related to IR or impaired insulin secretion. We speculate that the causal effects on monounsaturated fatty acid levels could explain parts of the raised cardiovascular disease risk in IR that is independent of diabetes development.

Detezione dei parametri temporali tramite sensori inerziali nello sprint: ottimizzazione e confronto di algoritmi proposti in letteratura per la corsa

In questo studio sono stati analizzati ed ottimizzati alcuni algoritmi proposti in letteratura per la detezione dei parametri temporali della corsa, con l'obiettivo di determinare quale, fra quelli proposti, sia il più affidabile per il suo utilizzo nell'analisi dello sprint. Per fare ciò, sono state condotte delle acquisizioni outdoor su cinque atleti differenti, utilizzando tre sensori inerziali IMU EXL-s3 (EXEL S.r.l., Bologna) con frequenza di acquisizione a 200 Hz, posizionati sul dorso dei due piedi e sul tronco (schiena, livello L1). Gli algoritmi confrontati sono stati sviluppati in ambiente MATLAB (MathWorks Inc., USA) e sono stati riferiti al gold standard di telecamera a 250 fps analizzando, per ciascuno, i limits of agreement. L'algoritmo implementato da Bergamini et al. (si veda l'articolo 'Estimation of temporal parameters during sprint running using a trunk-mounted inertial measurement unit') è risultato il migliore, con un bias di circa 0.005 s e limits of agreement entro gli 0.025 s fra i dati da sensore e il riferimento video, dati questi che confermano anche i risultati ottenuti da Bergamini et al.

An Interdisciplinary Approach to the Management of Vocal Cord Dysfunction in an Elite Female Swimmer: a Case Study

Acute pulmonary disorders are commonplace within the athletic population, with exercise induced bronchoconstriction (EIB), and vocal cord dysfunction (VCD) common diagnoses. VCD is a condition that causes the adduction of the vocal folds during inhalation, causing obstruction at the larynx and thereby a severely impaired sporting performance. VCD can be brought on by laryngeal irritants, emotional and psychological stress and asthma. The gold standard of treatment for VCD centres on an interdisciplinary approach from specialists that often include a respiratory consultant, speech and language therapist (SLT) and a psychologist. The present case study details the interdisciplinary approach to the treatment of an elite female swimmer with VCD with an intervention programme that lasted nine weeks, instigated by a local general practitioner (G.P.) who chose to engage a Sport Psychology Consultant (SPC) due to the sport-specific nature of the psychological stress experienced by the individual. The steps involved in the design of the sport psychology interventions are outlined and the relationship of those interventions to the work of the other specialists is discussed. The 9 week intervention programme was aimed at reducing perfectionist tendencies and competitive state anxiety using a combination of cognitive behavioural therapy (CBT), goal-setting and imagery. Overall, the treatment programme was deemed a success as perfectionism and competitive state anxiety levels reduced over time along with the frequency of VCD occurrence. This case study demonstrates the breadth of roles that can be undertaken by a SPC and raises awareness of a complex respiratory disorder that is not yet fully understood.

Comparative study of stereopsis with three different tests: TNO®, Stereo Acuity Test Fly® and StereoTAB® in students in higher school

Purpose: Stereopsis is the perception of depth based on retinal disparity. Global stereopsis depends on the process of random dot stimuli and local stereopsis depends on contour perception. The aim of this study was to correlate 3 stereopsis tests: TNO®, StereoTA B®, and Fly Stereo Acuity Test® and to study the sensitivity and correlation between them, using TNO® as the gold standard. Other variables as near convergence point, vergences, symptoms and optical correction were correlated with the 3 tests. Materials and Methods: Forty-nine students from Escola Superior de Tecnologia da Saúde de Lisboa (ESTeSL), aged 18-26 years old were included. Results: The stereopsis mean (standard-deviation-SD) values in each test were: TNO® = 87.04” ±84.09”; FlyTest® = 38.18” ±34.59”; StereoTA B® = 124.89’’ ±137.38’’. About the coefficient of determination: TNO® and StereoTA B® with R2 = 0.6 e TNO® and FlyTest® with R2 =0.2. Pearson correlation coefficient shows a positive correlation between TNO® and StereoTA B® (r = 0.784 with α = 0.01). Phi coefficient shows a strong and positive association between TNO® and StereoTA B® (Φ = 0.848 with α = 0.01). In the ROC Curve, the StereoTA B® has an area under the curve bigger than the FlyTest® with a sensivity of 92.3% for 94.4% of specificity, so it means that the test is sensitive with a good discriminative power. Conclusion: We conclude that the use of Stereopsis tests to study global Stereopsis are an asset for clinical use. This type of test is more sensitive, revealing changes in Stereopsis when it is actually changed, unlike the test Stereopsis, which often indicates normal Stereopsis, camouflaging a Stereopsis change. We noted also that the StereoTA B ® is very sensitive and despite being a digital application, possessed good correlation with the TNO®.

Laparoscopic versus open total mesorectal excision for stage I-III mid and low rectal cancer: a retrospective 5 years analysis

Introduction. Total mesorectal excision (TME) is the cornerstone of a correct surgical therapy for extraperitoneal rectal cancer. Aim of the study is to evaluate our 5 years experience confronting retrospectively laparoscopic (lap) TME in respect to its laparotomic (open) counterpart. Patients and Methods. 30 patients were treated laparoscopically for stage I-III extraperitoneal rectal cancer and retrospectively compared to a homogeneous group, stratified for sex, age, comorbidities and stage of disease. Results. 30 days mortality was zero for both groups, while morbidity was 20% for the lap group and 36.6% for the open group. Mean lymph nodes harvested was 24 ± 12 for the lap group, 26 ± 14 for the open group (p > 0.05). Five years overall and disease free survival was respectively 82.2% and 81.4% in the lap group, 79.9% and 79.6% in the open group, without statistical significance (p>0.05). Discussion. Minimally invasive TME resulted a safe, effective and oncologically adequate procedure when retrospectively compared to its laparotomic counterpart, with 5 years overall survival and disease free survival reaching no statistical significance compared to the open approach, but with all the advantages of the laparoscopy such as less pain and blood loss, faster recovery, less morbidity and better cosmetics. Conclusions. Our study has retrospectively demonstrated that laparoscopic TME is feasible and oncologically effective, even if it remains a complex minimally invasive procedure, requiring adequate skill. More prospective, randomized studies are necessary to define such a procedure as the new gold standard in treatment of stage I-III extraperitoneal rectal cancer.

Développement à visée clinique d’une prothèse vasculaire décellularisée de faible diamètre produite par génie tissulaire

Il existe un besoin clinique pour les prothèses vasculaires de faible diamètre (< 6 mm), notamment pour effectuer des pontages vasculaires. Les prothèses synthétiques de faible diamètre, n’ayant pas d’endothélium, sont sujettes à la thrombose. Ainsi les chirurgiens préfèrent utiliser les vaisseaux autologues des patients. Pour cela, la veine saphène est de loin la plus utilisée. Cependant, de nombreux patients n’ont pas de vaisseaux adéquats, soit parce qu’ils ont déjà été utilisés, soit parce qu’ils sont malades. Pour pallier ce manque, le LOEX a développé un substitut vasculaire reconstruit en laboratoire par la méthode d’auto-assemblage du génie tissulaire. Ces substituts, faits à partir de cellules humaines, ont une longue période de production et ne peuvent être faits à l’avance ni préservés. L’objectif principal de cette thèse est le développement d’une prothèse vasculaire de faible diamètre facilitant le transfert du laboratoire vers la clinique. S’inspirant de travaux antérieurs, les travaux focalisent sur des prothèses obtenues à partir de fibroblastes dermiques humains puis décellularisés. Comme la réponse immunitaire se fait principalement contre les cellules et non pas contre la matrice extracellulaire, la décellularisation permet de gagner une compatibilité immunitaire inter-individu, voire inter-espèce. Ainsi, des prothèses ont été implantées dans six rats pendant six mois sans immunosuppression avec un taux de succès de 83%. Les explants présentaient une infiltration cellulaire suggérant la formation d’une nouvelle media recouverte d’un endothélium. Par ailleurs, nous avons démontré qu’il était également possible de produire des prothèses de grandeur et diamètre adéquats pour une utilisation clinique. Ces prothèses ont été préservées durant trois mois sans altérer leurs propriétés mécaniques. Nous avons également endothélialisé des vaisseaux qui ont ensuite été conditionnés en bioréacteur durant une semaine. Le processus entraînait une compaction de la matrice extracellulaire et un gain dans la résistance à la traction du matériau. En conclusion, les prothèses vasculaires décellularisées offrent deux avantages majeurs facilitant ainsi les essais précliniques et accélérant leur transfert du laboratoire vers les patients.

Recurrent varicose veins of the legs. Analysis of a social problem

The present study was aimed at assessing the experience of a single referral center with recurrent varicose veins of the legs (RVL) over the period 1993-2008. Among a total of 846 procedures for Leg Varices (LV), 74 procedures were for RVL (8.7%). The causes of recurrence were classified as classic: insufficient crossectomy (13); incompetent perforating veins (13); reticular phlebectasia (22); small saphenous vein insufficiency (9); accessory saphenous veins (4); and particular: post-hemodynamic treatment (5); incomplete stripping (1); Sapheno-Femoral Junction (SFJ) vascularization (5); post-thermal ablation (2). For the “classic” RVL the treatment consisted essentially of completing the previous treatment, both if the problem was linked to an insufficient earlier treatment and if it was due to a later onset. The most common cause in our series was reticular phlebectasia; when the simple sclerosing injections are not sufficient, this was treated by phlebectomy according to Mueller. The “particular” cases classified as 1, 2 and 4 were also treated by completing the traditional stripping procedure (+ crossectomy if this had not been done previously), considered to be the gold standard. In the presence of a SFJ neo-vascularization, with or without cavernoma, approximately 5 cm of femoral vein were explored, the afferent vessels ligated and, if cavernoma was present, it was removed. Although inguinal neo-angiogenesis is a possible mechanism, some doubt can be raised as to its importance as a primary factor in causing recurrent varicose veins, rather than their being due to a preexisting vein left in situ because it was ignored, regarded as insignificant, or poorly evident. In conclusion, we stress that LV is a progressive disease, so the treatment is unlikely to be confined to a single procedure. It is important to plan adequate monitoring during follow-up, and to be ready to reoperate when new problems present that, if left, could lead the patient to doubt the validity and efficacy of the original treatment.

Registration-by-regression of coronary CTA and X-ray angiography

We evaluate the integration of 3D preoperative computed tomography angiography of the coronary arteries with intraoperative 2D X-ray angiographies by a recently proposed novel registration-by-regression method. The method relates image features of 2D projection images to the transformation parameters of the 3D image. We compared different sets of features and studied the influence of preprocessing the training set. For the registration evaluation, a gold standard was developed from eight X-ray angiography sequences from six different patients. The alignment quality was measured using the 3D mean target registration error (mTRE). The registration-by-regression method achieved moderate accuracy (median mTRE of 15 mm) on real images. It does therefore not provide yet a complete solution to the 3D–2D registration problem but it could be used as an initialisation method to eliminate the need for manual initialisation.

Estudo comparativo da estereopsia com três testes diferentes: TNO®, Fly Stereo Acuity Test® e StereoTAB® em estudantes do ensino superior

Estereopsia define-se como a perceção de profundidade baseada na disparidade retiniana. A estereopsia global depende do processamento de estímulos de pontos aleatórios e a estereopsia local depende da perceção de contornos. O objetivo deste estudo é correlacionar três testes de estereopsia: TNO®, StereoTAB® e Fly Stereo Acuity Test® e verificar a sensibilidade e correlação entre eles, tendo o TNO® como gold standard. Incluíram-se 49 estudantes da Escola Superior de Tecnologia da Saúde de Lisboa (ESTeSL) entre os 18 e 26 anos. As variáveis ponto próximo de convergência (ppc), vergências, sintomatologia e correção ótica foram correlacionadas com os três testes. Os valores médios (desvios-padrão) de estereopsia foram: TNO® = 87,04’’ ±84,09’’; FlyTest® = 38,18’’ ±34,59’’; StereoTAB® = 124,89’’ ±137,38’’. Coeficiente de determinação: TNO® e StereoTAB® com R2=0,6 e TNO® e FlyTest® com R2=0,2. O coeficiente de correlação de Pearson mostra uma correlação positiva de entre o TNO® e o StereoTAB® (r=0,784 com α=0,01). O coeficiente de associação de Phi mostrou uma relação positiva forte entre o TNO® e StereoTAB® (Φ=0,848 com α=0,01). Na curva ROC, o StereoTAB® possui uma área sob a curva maior que o FlyTest®, apresentando valor de sensibilidade de 92,3% para uma especificidade de 94,4%, tornando-o num teste sensível e com bom poder discriminativo.