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.

Improving risk stratification in non-ST-segment elevation myocardial infarction with combined assessment of GRACE and CRUSADE risk scores

BACKGROUND: Risk assessment is fundamental in the management of acute coronary syndromes (ACS), enabling estimation of prognosis. AIMS: To evaluate whether the combined use of GRACE and CRUSADE risk stratification schemes in patients with myocardial infarction outperforms each of the scores individually in terms of mortality and haemorrhagic risk prediction. METHODS: Observational retrospective single-centre cohort study including 566 consecutive patients admitted for non-ST-segment elevation myocardial infarction. The CRUSADE model increased GRACE discriminatory performance in predicting all-cause mortality, ascertained by Cox regression, demonstrating CRUSADE independent and additive predictive value, which was sustained throughout follow-up. The cohort was divided into four different subgroups: G1 (GRACE<141; CRUSADE<41); G2 (GRACE<141; CRUSADE≥41); G3 (GRACE≥141; CRUSADE<41); G4 (GRACE≥141; CRUSADE≥41). RESULTS: Outcomes and variables estimating clinical severity, such as admission Killip-Kimbal class and left ventricular systolic dysfunction, deteriorated progressively throughout the subgroups (G1 to G4). Survival analysis differentiated three risk strata (G1, lowest risk; G2 and G3, intermediate risk; G4, highest risk). The GRACE+CRUSADE model revealed higher prognostic performance (area under the curve [AUC] 0.76) than GRACE alone (AUC 0.70) for mortality prediction, further confirmed by the integrated discrimination improvement index. Moreover, GRACE+CRUSADE combined risk assessment seemed to be valuable in delineating bleeding risk in this setting, identifying G4 as a very high-risk subgroup (hazard ratio 3.5; P<0.001). CONCLUSIONS: Combined risk stratification with GRACE and CRUSADE scores can improve the individual discriminatory power of GRACE and CRUSADE models in the prediction of all-cause mortality and bleeding. This combined assessment is a practical approach that is potentially advantageous in treatment decision-making.

Effet préventif de la milrinone inhalée chez les patients avec hypertension pulmonaire subissant une chirurgie cardiaque sous circulation extracorporelle : une approche pharmacométrique

La circulation extracorporelle (CEC) est une technique utilisée en chirurgie cardiaque effectuée des milliers de fois chaque jour à travers le monde. L’instabilité hémodynamique associée au sevrage de la CEC difficile constitue la principale cause de mortalité en chirurgie cardiaque et l’hypertension pulmonaire (HP) a été identifiée comme un des facteurs de risque les plus importants. Récemment, une hypothèse a été émise suggérant que l'administration prophylactique (avant la CEC) de la milrinone par inhalation puisse avoir un effet préventif et faciliter le sevrage de la CEC chez les patients atteints d’HP. Toutefois, cette indication et voie d'administration pour la milrinone n'ont pas encore été approuvées par les organismes réglementaires. Jusqu'à présent, la recherche clinique sur la milrinone inhalée s’est principalement concentrée sur l’efficacité hémodynamique et l'innocuité chez les patients cardiaques, bien qu’aucun biomarqueur n’ait encore été établi. La dose la plus appropriée pour l’administration par nébulisation n'a pas été déterminée, de même que la caractérisation des profils pharmacocinétiques (PK) et pharmacodynamiques (PD) suite à l'inhalation. L'objectif de notre recherche consistait à caractériser la relation exposition-réponse de la milrinone inhalée administrée chez les patients subissant une chirurgie cardiaque sous CEC. Une méthode analytique par chromatographie liquide à haute performance couplée à un détecteur ultraviolet (HPLC-UV) a été optimisée et validée pour le dosage de la milrinone plasmatique suite à l’inhalation et s’est avérée sensible et précise. La limite de quantification (LLOQ) était de 1.25 ng/ml avec des valeurs de précision intra- et inter-dosage moyennes (CV%) <8%. Des patients souffrant d’HP pour lesquels une chirurgie cardiaque sous CEC était prévue ont d’abord été recrutés pour une étude pilote (n=12) et, par la suite, pour une étude à plus grande échelle (n=28) où la milrinone (5 mg) était administrée par inhalation pré-CEC. Dans l'étude pilote, nous avons comparé l'exposition systémique de la milrinone peu après son administration avec un nébuliseur pneumatique ou un nébuliseur à tamis vibrant. L’efficacité des nébuliseurs en termes de dose émise et dose inhalée a également été déterminée in vitro. Dans l'étude à plus grande échelle conduite en utilisant exclusivement le nébuliseur à tamis vibrant, la dose inhalée in vivo a été estimée et le profil pharmacocinétique de la milrinone inhalée a été pleinement caractérisé aux niveaux plasmatique et urinaire. Le ratio de la pression artérielle moyenne sur la pression artérielle pulmonaire moyenne (PAm/PAPm) a été choisi comme biomarqueur PD. La relation exposition-réponse de la milrinone a été caractérisée pendant la période d'inhalation en étudiant la relation entre l'aire sous la courbe de l’effet (ASCE) et l’aire sous la courbe des concentrations plasmatiques (ASC) de chacun des patients. Enfin, le ratio PAm/PAPm a été exploré comme un prédicteur potentiel de sortie de CEC difficile dans un modèle de régression logistique. Les expériences in vitro ont démontré que les doses émises étaient similaires pour les nébuliseurs pneumatique (64%) et à tamis vibrant (68%). Cependant, la dose inhalée était 2-3 fois supérieure (46% vs 17%) avec le nébuliseur à tamis vibrant, et ce, en accord avec les concentrations plasmatiques. Chez les patients, en raison des variations au niveau des facteurs liés au circuit et au ventilateur causant une plus grande dose expirée, la dose inhalée a été estimée inférieure (30%) et cela a été confirmé après récupération de la dose de milrinone dans l'urine 24 h (26%). Les concentrations plasmatiques maximales (Cmax: 41-189 ng/ml) et l'ampleur de la réponse maximale ΔRmax-R0 (0-65%) ont été observées à la fin de l'inhalation (10-30 min). Les données obtenues suite aux analyses PK sont en accord avec les données publiées pour la milrinone intraveineuse. Après la période d'inhalation, les ASCE individuelles étaient directement reliées aux ASC (P=0.045). Enfin, notre biomarqueur PD ainsi que la durée de CEC ont été identifiés comme des prédicteurs significatifs de la sortie de CEC difficile. La comparaison des ASC et ASCE correspondantes a fourni des données préliminaires supportant une preuve de concept pour l'utilisation du ratio PAm/PAPm comme biomarqueur PD prometteur et justifie de futures études PK/PD. Nous avons pu démontrer que la variation du ratio PAm/PAPm en réponse à la milrinone inhalée contribue à la prévention de la sortie de CEC difficile.

The study of the sedimentation mechanism in channels under the impact of tidal currents

The purpose of this research is to study sedimentation mechanism by mathematical modeling in access channels which are affected by tidal currents. The most important factor for recognizing sedimentation process in every water environment is the flow pattern of that environment. It is noteworthy that the flow pattern is affected by the geometry and the shape of the environment as well as the type of existing affects in area. The area under the study in this thesis is located in Bushehr Gulf and the access channels (inner and outer). The study utilizes the hydrodynamic modeling with unstructured triangular and non-overlapping grids, using the finite volume, From method analysis in two scale sizes: large scale (200 m to 7.5km) and small scale (50m to 7.5km) in two different time durations of 15 days and 3.5 days to obtain the flow patterns. The 2D governing equations used in the model are the Depth-Averaged Shallow Water Equations. Turbulence Modeling is required to calculate the Eddy Viscosity Coefficient using the Smagorinsky Model with coefficient of 0.3. In addition to the flow modeling in two different scales and the use of the data of 3.5 day tidal current modeling have been considered to study the effects of the sediments equilibrium in the area and the channels. This model is capable of covering the area which is being settled and eroded and to identify the effects of tidal current of these processes. The required data of the above mentioned models such as current and sediments data have been obtained by the measurements in Bushehr Gulf and the access channels which was one of the PSO's (Port and Shipping Organization) project-titled, "The Sedimentation Modeling in Bushehr Port" in 1379. Hydrographic data have been obtained from Admiralty maps (2003) and Cartography Organization (1378, 1379). The results of the modeling includes: cross shore currents in northern and north western coasts of Bushehr Gulf during the neap tide and also the same current in northern and north eastern coasts of the Gulf during the spring tide. These currents wash and carry fine particles (silt, clay, and mud) from the coastal bed of which are generally made of mud and clay with some silts. In this regard, the role of sediments in the islands of this area and the islands made of depot of dredged sediments should not be ignored. The result of using 3.5 day modeling is that the cross channels currents leads to settlement places in inner and outer channels in tidal period. In neap tide the current enters the channel from upside bend of the two channels and outer channel. Then it crosses the channel oblique in some places of the outer channel. Also the oblique currents or even almost perpendicular current from up slope of inner channel between No. 15 and No. 18 buoys interact between the parallel currents in the channel and made secondary oblique currents which exit as a down-slope current in the channel and causes deposit of sediments as well as settling the suspended sediments carried by these currents. In addition in outer channel the speed of parallel currents in the bend of the channel which is naturally deeper increases. Therefore, it leads to erosion and suspension of sediments in this area. The speed of suspended sediments carried by this current which is parallel to the channel axis decreases when they pass through the shallower part of the channel where it is in the buoys No.7 and 8 to 5 and 6 are located. Therefore, the suspended sediment settles and because of this process these places will be even shallower. Furthermore, the passing of oblique upstream leads to settlement of the sediments in the up-slope and has an additional effect on the process of decreasing the depth of these locations. On the contrary, in the down-slope channel, as the results of sediments and current modeling indicates the speed of current increases and the currents make the particles of down-slope channel suspended and be carried away. Thus, in a vast area of downstream of both channels, the sediments have settled. At the end of the neap tide, the process along with circulations in this area produces eddies which causes sedimentation in the area. During spring some parts of this active location for sedimentation will enter both channels in a reverse process. The above mentioned processes and the places of sedimentation and erosion in inner and outer channels are validated by the sediments equilibrium modeling. This model will be able to estimate the suspended, bed load and the boundary layer thickness in each point of both channels and in the modeled area.

Improving the use of G-CSF during chemotherapy using physiological mathematical modelling : a quantitative systems pharmacology approach

La diminution des doses administrées ou même la cessation complète d'un traitement chimiothérapeutique est souvent la conséquence de la réduction du nombre de neutrophiles, qui sont les globules blancs les plus fréquents dans le sang. Cette réduction dans le nombre absolu des neutrophiles, aussi connue sous le nom de myélosuppression, est précipitée par les effets létaux non spécifiques des médicaments anti-cancéreux, qui, parallèlement à leur effet thérapeutique, produisent aussi des effets toxiques sur les cellules saines. Dans le but d'atténuer cet impact myélosuppresseur, on administre aux patients un facteur de stimulation des colonies de granulocytes recombinant humain (rhG-CSF), une forme exogène du G-CSF, l'hormone responsable de la stimulation de la production des neutrophiles et de leurs libération dans la circulation sanguine. Bien que les bienfaits d'un traitement prophylactique avec le G-CSF pendant la chimiothérapie soient bien établis, les protocoles d'administration demeurent mal définis et sont fréquemment déterminés ad libitum par les cliniciens. Avec l'optique d'améliorer le dosage thérapeutique et rationaliser l'utilisation du rhG-CSF pendant le traitement chimiothérapeutique, nous avons développé un modèle physiologique du processus de granulopoïèse, qui incorpore les connaissances actuelles de pointe relatives à la production des neutrophiles des cellules souches hématopoïétiques dans la moelle osseuse. À ce modèle physiologique, nous avons intégré des modèles pharmacocinétiques/pharmacodynamiques (PK/PD) de deux médicaments: le PM00104 (Zalypsis®), un médicament anti-cancéreux, et le rhG-CSF (filgrastim). En se servant des principes fondamentaux sous-jacents à la physiologie, nous avons estimé les paramètres de manière exhaustive sans devoir recourir à l'ajustement des données, ce qui nous a permis de prédire des données cliniques provenant de 172 patients soumis au protocol CHOP14 (6 cycles de chimiothérapie avec une période de 14 jours où l'administration du rhG-CSF se fait du jour 4 au jour 13 post-chimiothérapie). En utilisant ce modèle physio-PK/PD, nous avons démontré que le nombre d'administrations du rhG-CSF pourrait être réduit de dix (pratique actuelle) à quatre ou même trois administrations, à condition de retarder le début du traitement prophylactique par le rhG-CSF. Dans un souci d'applicabilité clinique de notre approche de modélisation, nous avons investigué l'impact de la variabilité PK présente dans une population de patients, sur les prédictions du modèle, en intégrant des modèles PK de population (Pop-PK) des deux médicaments. En considérant des cohortes de 500 patients in silico pour chacun des cinq scénarios de variabilité plausibles et en utilisant trois marqueurs cliniques, soient le temps au nadir des neutrophiles, la valeur du nadir, ainsi que l'aire sous la courbe concentration-effet, nous avons établi qu'il n'y avait aucune différence significative dans les prédictions du modèle entre le patient-type et la population. Ceci démontre la robustesse de l'approche que nous avons développée et qui s'apparente à une approche de pharmacologie quantitative des systèmes (QSP). Motivés par l'utilisation du rhG-CSF dans le traitement d'autres maladies, comme des pathologies périodiques telles que la neutropénie cyclique, nous avons ensuite soumis l'étude du modèle au contexte des maladies dynamiques. En mettant en évidence la non validité du paradigme de la rétroaction des cytokines pour l'administration exogène des mimétiques du G-CSF, nous avons développé un modèle physiologique PK/PD novateur comprenant les concentrations libres et liées du G-CSF. Ce nouveau modèle PK a aussi nécessité des changements dans le modèle PD puisqu’il nous a permis de retracer les concentrations du G-CSF lié aux neutrophiles. Nous avons démontré que l'hypothèse sous-jacente de l'équilibre entre la concentration libre et liée, selon la loi d'action de masse, n'est plus valide pour le G-CSF aux concentrations endogènes et mènerait en fait à la surestimation de la clairance rénale du médicament. En procédant ainsi, nous avons réussi à reproduire des données cliniques obtenues dans diverses conditions (l'administration exogène du G-CSF, l'administration du PM00104, CHOP14). Nous avons aussi fourni une explication logique des mécanismes responsables de la réponse physiologique aux deux médicaments. Finalement, afin de mettre en exergue l’approche intégrative en pharmacologie adoptée dans cette thèse, nous avons démontré sa valeur inestimable pour la mise en lumière et la reconstruction des systèmes vivants complexes, en faisant le parallèle avec d’autres disciplines scientifiques telles que la paléontologie et la forensique, où une approche semblable a largement fait ses preuves. Nous avons aussi discuté du potentiel de la pharmacologie quantitative des systèmes appliquées au développement du médicament et à la médecine translationnelle, en se servant du modèle physio-PK/PD que nous avons mis au point.

Études in vivo et in vitro sur le potentiel néphroprotecteur de plantes médicinales anti-diabétiques de la pharmacopée traditionnelle des Cris de la Baie-James

Notre équipe a identifié le thé Labrador [Rhododendron groenlandicum L. (Ericaceae)] comme une plante potentiellement antidiabétique de la pharmacopée traditionnelle des Cris de la Baie James orientale. Dans la présente étude, nous avons évalué les effets néphroprotecteurs potentiels de la plante. De la microalbuminurie et de la fibrose rénale ont été développées chez des souris alimentées avec une diète grasse (DG). Le R. groenlandicum améliore d’une façon non-significative la microalbuminurie, avec des valeurs de l’aire sous la courbe (ACR) diminuant de 0.69 à 0.53. La valeur de la fibrose rénale qui était, à l’origine, de 4.85 unités arbitraires (UA) dans des souris alimentées à la DG, a chuté à 3.27 UA après avoir reçu un traitement de R. groenlandicum. Le R. groenlandicum a réduit la stéatose rénale de presque la moitié alors que l’expression du facteur de modification Bcl-2 (Bmf) a chuté de 13.96 UA à 9.43 UA. Dans leur ensemble les résultats suggèrent que le traitement avec R. groenlandicum peut améliorer la fonction rénale altérée par DG. Dans l’étude subséquente, notre équipe a identifié 17 espèces de la forêt boréale, de la pharmacopée traditionnelle des Cris de la Baie James orientale, qui ont présenté des activités biologiques prometteuses in vitro et in vivo dans le contexte du DT2. Nous avons maintenant examiné ces 17 extraits afin d’identifier lesquels possèdent un potentiel cytoprotecteur rénale en utilisant des cellules Madin Darby Canine Kidney (MDCK) mises à l’épreuve dans un médium hypertonique. Nous concluons que plusieurs plantes antidiabétiques Cris exercent une activité de protection rénale qui pourrait être pertinente dans le contexte de la néphropathie diabétique (ND) qui affecte une proportion importante des Cris. La G. hispidula et la A. balsamea sont parmi les plantes les plus puissantes dans ce contexte et elles semblent protectrices principalement en inhibant la caspase 9 dans la voie de signalisation apoptotique mitochondriale. Finalement, nous avons utilisé une approche de fractionnement guidée par un test biologique pour identifier les fractions actives et les composés de A. balsamea avec un potentiel de protection rénale in vitro dans des cellules MDCK mises au défi avec un médium hypertonique. La fraction d’hexane (Hex) possède le potentiel le plus élevé parmi toutes les fractions de solvant contre les dommages cellulaires induits par le stress hypertonique. Dans des études précédentes, trois composés purs ont été identifiés à partir de la fraction Hex, à savoir, l’acide abiétique, l’acide déhydroabiétique et le squalène. L’acide abiétique se distinguait par son effet puissant dans le maintien de la viabilité des cellules MDCK (AnnV-/PI-) à un niveau relativement élevé (augmentation de 25.48% relative au stress hypertonique, P<0.0001), ainsi qu’une réduction significative (diminution de 20.20% par rapport au stress hypertonique, P<0.0001) de l’apoptose de stade précoce (AnnV+/PI-). L’acide abiétique peut donc servir à normaliser les préparations traditionnelles d’A. balsamea et à trouver des applications potentielles dans le traitement de la néphropathie diabétique. Les trois études ont été intrinsèquement liées les unes aux autres, par conséquent, nous avons réussi à identifier R. groenlandicum ainsi que A. balsamea comme nouvelles plantes prometteuses contre la néphropathie diabétique. Nous croyons que ces résultats profiteront à la communauté crie pour la gestion des complications diabétiques, en particulier la néphropathie diabétique. En parallèle, nos données pourraient faire avancer l'essai clinique de certaines plantes médicinales de la pharmacopée traditionnelle des Cris de la Baie James orientale du Canada.

Pharmacokinetic Profile of Liposome-Encapsulated Ropivacaine after Maxillary Infiltration Anaesthesia

The aim of this study was to determine the pharmacokinetic parameters of liposomal ropivacaine after dental anesthesia in 14 healthy volunteers. In this randomized, double-blind and crossover study, the volunteers received maxillary infiltration of liposome-encapsulated 0.5% ropivacaine and, 0.5% ropivacaine with 1:200,000 epinephrine in two different sessions. Blood samples were collected before and after (from 15 to 1440 min) the administration of either ropivacaine formulation. HPLC with UV detection was used to quantify plasma ropivacaine concentrations. The pharmacokinetic parameters AUC(0-24) (area under the plasma concentration x time curve from baseline to 24 h), AUC(0-infinity) (area under the plasma concentration-time curve from baseline to infinity), C-max (maximum drug concentration), CL (renal clearance), T-max (maximum drug concentration time), t(1/2) (elimination half-life) and Vd (volume of distribution) were analyzed using the Wilcoxon signed-rank test. No differences (p > 0.05) were observed between both formulations for any of the pharmacokinetic parameters evaluated and plasma ropivacaine concentrations, considering each period of time. Both formulations showed similar pharmacokinetic profiles, indicating that the liposomal formulation could be a safer option for use of this local anesthetic, due to the absence of a vasoconstrictor.

Impaired Mesopic Visual Acuity in Eyes with Early Age-Related Macular Degeneration

Purpose.: To determine photopic and mesopic distance high-contrast visual acuity (HC-VA) and low-contrast visual acuity (LC-VA) in eyes with early age-related macular degeneration (AMD). Methods.: Measurements were made in 22 subjects with early AMD and 28 healthy control subjects. Inclusion criteria included a photopic HC-VA of 20/25 or better. Distance VA was measured using HC (96%) and LC (10%) Bailey-Lovie logMAR letter charts under photopic (85 cd/m2) and mesopic (0.1–0.2 cd/m2) luminance conditions. Results.: Mean mesopic distance HC-VA and LC-VA were significantly worse (0.1 logMAR and 0.28 logMAR, respectively) in the early AMD group than in the control group. Under mesopic conditions, the mean difference between LC-VA and HC-VA was significantly greater in the early AMD (0.45 logMAR) than the control group (0.27 logMAR). Mean differences between mesopic versus photopic HC-VA and mesopic versus photopic LC-VA were significantly greater in the early AMD than the control group (0.13 and 0.32 logMAR of difference between the means, respectively). Sensitivity and specificity were significantly greater for mesopic LC-VA than for mesopic HC-VA (Receiver Operating Characteristics, area under the curve [AUC], 0.94 ± 0.030 and 0.76 ± 0.067, respectively). AUC values for photopic HC-VA and LC-VA were below 0.70. Conclusions.: Visual acuity testing under low luminance conditions emerged as an optimal quantitative measure of retinal function in early AMD.

Bioequivalence evaluation of new microparticulate capsule and marketed tablet dosage forms of lornoxicam in healthy volunteers

Purpose: To compare oral bioavailability and pharmacokinetic parameters of different lornoxicam formulations and to assess similarity in plasma level profiles by statistical techniques. Methods: An open-label, two-period crossover trial was followed in 24 healthy Pakistani volunteers (22 males, 2 females). Each participant received a single dose of lornoxicam controlled release (CR) microparticles and two doses (morning and evening) of conventional lornoxicam immediate release (IR) tablet formulation. The microparticles were prepared by spray drying method. The formulations were administered again in an alternate manner after a washout period of one week. Pharmacokinetic parameters were determined by Kinetica 4.0 software using plasma concentration-time data. Moreover, data were statistically analyzed at 90 % confidence interval (CI) and Schuirmann’s two one-sided t-test procedure. Results: Peak plasma concentration (Cmax) was 20.2 % lower for CR formulation compared to IR formulation (270.90 ng/ml vs 339.44 ng/ml, respectively) while time taken to attain Cmax (tmax) was 5.25 and 2.08 h, respectively. Area under the plasma drug level versus time (AUC) curve was comparable for both CR and IR formulations. The 90 % confidence interval (CI) values computed for Cmax, AUC0-24, and AUC0-∞ , after log transformation, were 87.21, 108.51 and 102.74 %, respectively, and were within predefined bioequivalence range (80 - 125 %). Conclusion: The findings suggest that CR formulation of lornoxicam did not change the overall pharmacokinetic properties of lornoxicam in terms of extent and rate of lornoxicam absorption.

Off-line and On-line Affective Recognition of a Computer User through A Biosignal Processing Approach

Physiological signals, which are controlled by the autonomic nervous system (ANS), could be used to detect the affective state of computer users and therefore find applications in medicine and engineering. The Pupil Diameter (PD) seems to provide a strong indication of the affective state, as found by previous research, but it has not been investigated fully yet. In this study, new approaches based on monitoring and processing the PD signal for off-line and on-line affective assessment (“relaxation” vs. “stress”) are proposed. Wavelet denoising and Kalman filtering methods are first used to remove abrupt changes in the raw Pupil Diameter (PD) signal. Then three features (PDmean, PDmax and PDWalsh) are extracted from the preprocessed PD signal for the affective state classification. In order to select more relevant and reliable physiological data for further analysis, two types of data selection methods are applied, which are based on the paired t-test and subject self-evaluation, respectively. In addition, five different kinds of the classifiers are implemented on the selected data, which achieve average accuracies up to 86.43% and 87.20%, respectively. Finally, the receiver operating characteristic (ROC) curve is utilized to investigate the discriminating potential of each individual feature by evaluation of the area under the ROC curve, which reaches values above 0.90. For the on-line affective assessment, a hard threshold is implemented first in order to remove the eye blinks from the PD signal and then a moving average window is utilized to obtain the representative value PDr for every one-second time interval of PD. There are three main steps for the on-line affective assessment algorithm, which are preparation, feature-based decision voting and affective determination. The final results show that the accuracies are 72.30% and 73.55% for the data subsets, which were respectively chosen using two types of data selection methods (paired t-test and subject self-evaluation). In order to further analyze the efficiency of affective recognition through the PD signal, the Galvanic Skin Response (GSR) was also monitored and processed. The highest affective assessment classification rate obtained from GSR processing is only 63.57% (based on the off-line processing algorithm). The overall results confirm that the PD signal should be considered as one of the most powerful physiological signals to involve in future automated real-time affective recognition systems, especially for detecting the “relaxation” vs. “stress” states.

Detection and Grading of Prostate Cancer in Temporal Enhanced Ultrasound using Convolutional Neural Networks

Prostate cancer is the most common non-dermatological cancer amongst men in the developed world. The current definitive diagnosis is core needle biopsy guided by transrectal ultrasound. However, this method suffers from low sensitivity and specificity in detecting cancer. Recently, a new ultrasound based tissue typing approach has been proposed, known as temporal enhanced ultrasound (TeUS). In this approach, a set of temporal ultrasound frames is collected from a stationary tissue location without any intentional mechanical excitation. The main aim of this thesis is to implement a deep learning-based solution for prostate cancer detection and grading using TeUS data. In the proposed solution, convolutional neural networks are trained to extract high-level features from time domain TeUS data in temporally and spatially adjacent frames in nine in vivo prostatectomy cases. This approach avoids information loss due to feature extraction and also improves cancer detection rate. The output likelihoods of two TeUS arrangements are then combined to form our novel decision support system. This deep learning-based approach results in the area under the receiver operating characteristic curve (AUC) of 0.80 and 0.73 for prostate cancer detection and grading, respectively, in leave-one-patient-out cross-validation. Recently, multi-parametric magnetic resonance imaging (mp-MRI) has been utilized to improve detection rate of aggressive prostate cancer. In this thesis, for the first time, we present the fusion of mp-MRI and TeUS for characterization of prostate cancer to compensates the deficiencies of each image modalities and improve cancer detection rate. The results obtained using TeUS are fused with those attained using consolidated mp-MRI maps from multiple MR modalities and cancer delineations on those by multiple clinicians. The proposed fusion approach yields the AUC of 0.86 in prostate cancer detection. The outcomes of this thesis emphasize the viable potential of TeUS as a tissue typing method. Employing this ultrasound-based intervention, which is non-invasive and inexpensive, can be a valuable and practical addition to enhance the current prostate cancer detection.

Maltodextrin-incorporated-vacuum-dried honey powder: processing and stability

Honey is rich in sugar content and dominated by fructose and glucose that make honey prone to crystallize during storage. Due to honey composition, the anhydrous glass transition temperature of honey is very low that makes honey difficult to dry alone and drying aid or filler is needed to dry honey. Maltodextrin is a common drying aid material used in drying of sugar-rich food. The present study aims to study the processing of honey powder by vacuum drying method and the impact of drying process and formulation on the stability of honey powder. To achieve the objectives, the series of experiments were done: investigating of maltodextrin DE 10 properties, studying the effect of drying temperature, total solid concentration, DE value, maltodextrin concentration and anti-caking agent on honey powder processing and stability. Maltodextrin provide stable glass compared to lower molecular weight sugars. Dynamic Dew Point Isotherm (DDI) data could be used to determine amorphous content of a system. The area under the first derivative curve from DDI curve is equal to the amount of water needed by amorphous material to crystallize. The drying temperature affected the amorphous content of vacuum-dried honey powder. The higher temperature seemed to result in honey powder with more amorphous component. The ratio of maltodextrin affected more significantly the stability of honey powder compared to the treatments of total solids concentration, DE value and drying temperature. The critical water activity of honey powder was lower than water activity of the equilibrium water content corresponding to BET monolayer water content. Addition of anti-caking agent increased stability and flow-ability of honey powder. Addition of Calcium stearate could inhibit collapse of the honey powder during storage.

Utilización de antimicrobianos en las infecciones odontogénicas en niños y adolescentes: análisis farmacocinético/farmacodinámico (PK/PD)

El objetivo de este estudio es evaluar la eficacia de los tratamientos más utilizados en infecciones odontogénicas en niños y adolescentes aplicando criterios farmacocinéticos/farmacodinámicos (PK/PD). Se han simulado las curvas de concentración plasmática libre-tiempo a partir de parámetros farmacocinéticos medios de amoxicilina, amoxicilina-ácido clavulánico, cefuroxima axetilo, espiramicina, clindamicina, azitromicina y metronidazol. Para los antibióticos con actividad dependiente del tiempo, se ha calculado el tiempo durante el cual las concentraciones permanecen por encima de la concentración inhibitoria mínima (CIM90) de los microorganismos (T>CIM). Para los antimicrobianos con actividad dependiente de la concentración, se ha calculado el cociente entre el área bajo la curva y la CIM90 (ABC/CIM90). Con amoxicilina-ácido clavulánico (80 mg/kg/día) se han obtenido índices de eficacia adecuados frente a los microorganismos estudiados (T > CIM > 40%), excepto paraVeillonella spp. Clindamicina (40 mg/kg/día) también ha presentado índices PK/PD adecuados frente a la mayoría de los patógenos, excepto Lactobacillus, Actinobacillus actinomycetemcomitans, Peptostreptococcus resistente a penicilina y Eikenella corrodens. Con dosis altas de amoxicilina los resultados no han sido satisfactorios frente a varias especies bacterianas. Con azitromicina y metronidazol no se han alcanzado valores adecuados frente a la mayoría de patógenos (ABC/CIM90 < 25). En conclusión, el tratamiento empírico más adecuado en infecciones odontogénicas en niños y adolescentes es amoxicilina-ácido clavulánico en altas dosis de amoxicilina, aunque se puede utilizar como alternativa clindamicina. Sería conveniente confirmar estos resultados mediante ensayos clínicos, para cuyo diseño y evaluación podría ser de gran utilidad la aplicación de estudios PK/PD.

Early intravenous beta-blockers in patients with ST-segment elevation myocardial infarction before primary percutaneous coronary intervention

The impact of intravenous (IV) beta-blockers before primary percutaneous coronary intervention (PPCI) on infarct size and clinical outcomes is not well established. This study sought to conduct the first double-blind, placebo-controlled international multicenter study testing the effect of early IV beta-blockers before PPCI in a general ST-segment elevation myocardial infarction (STEMI) population. STEMI patients presenting <12 h from symptom onset in Killip class I to II without atrioventricular block were randomized 1:1 to IV metoprolol (2 × 5-mg bolus) or matched placebo before PPCI. Primary endpoint was myocardial infarct size as assessed by cardiac magnetic resonance imaging (CMR) at 30 days. Secondary endpoints were enzymatic infarct size and incidence of ventricular arrhythmias. Safety endpoints included symptomatic bradycardia, symptomatic hypotension, and cardiogenic shock. A total of 683 patients (mean age 62 ± 12 years; 75% male) were randomized to metoprolol (n = 336) or placebo (n = 346). CMR was performed in 342 patients (54.8%). Infarct size (percent of left ventricle [LV]) by CMR did not differ between the metoprolol (15.3 ± 11.0%) and placebo groups (14.9 ± 11.5%; p = 0.616). Peak and area under the creatine kinase curve did not differ between both groups. LV ejection fraction by CMR was 51.0 ± 10.9% in the metoprolol group and 51.6 ± 10.8% in the placebo group (p = 0.68). The incidence of malignant arrhythmias was 3.6% in the metoprolol group versus 6.9% in placebo (p = 0.050). The incidence of adverse events was not different between groups. In a nonrestricted STEMI population, early intravenous metoprolol before PPCI was not associated with a reduction in infarct size. Metoprolol reduced the incidence of malignant arrhythmias in the acute phase and was not associated with an increase in adverse events.

LMS tables for waist circumference and waist-to-height ratio among Colombian children and adolescents: The FUPRECOL study

Background: Indices predictive of central obesity include waist circumference (WC) and waist-to-height ratio (WHtR). The aims of this study were 1) to establish a Colombian youth smoothed centile charts and LMS tables for WC and WHtR and 2) to evaluate the utility of these parameters as predictors of overweight and obesity. Method: A cross-sectional study whose sample population comprised 7954 healthy Colombian schoolchildren [boys n=3460 and girls n=4494, mean (standard deviation) age 12.8 (2.3) years old]. Weight, height, body mass index (BMI), WC and WHtR and its percentiles were calculated. Appropriate cut-offs point of WC and WHtR for overweight and obesity, as defined by the International Obesity Task Force (IOTF) definitions, were selected using receiver operating characteristic (ROC) analysis. The discriminating power of WC and WHtR was expressed as area under the curve (AUC). Results: Reference values for WC and WHtR are presented. Mean WC increased and WHtR decreased with age for both genders. We found a moderate positive correlation between WC and BMI (r= 0.756, P < 0.01) and WHtR and BMI (r= 0.604, P < 0.01). The ROC analysis showed a high discrimination power in the identification of overweight and obesity for both measures in our sample population. Overall, WHtR was slightly a better predictor for overweight/obesity (AUC 95% CI 0.868-0.916) than the WC (AUC 95% CI 0.862-0.904). Conclusion: This paper presents the first sex- and age-specific WC and WHtR percentiles for both measures among Colombian children and adolescents aged 9–17.9 years. By providing LMS tables for Latin-American people based on Colombian reference data, we hope to provide quantitative tools for the study of obesity and its comorbidities.