Inference on Cure Rate Under Multivariate Random Censoring

In survival studies, it is often of interest to study cure rates. Sometimes the event of interest (such as death or the occurrence of a disease) may not be experienced by individuals under study, and the cure rate is the probability of the latter eventuality. Furthermore, survival times (i.e., the time to the event of interest) may be subject to random censoring due to dropping out or late entry of individuals during the study period. Interestingly, random censoring facilitates the estimation of the cure rate. In this research, we study cure rates for multivariate survival times under multivariate random censoring. Specifically, three topics have been studied. In the first topic of this thesis, a new non-parametric multivariate cure rate estimator, based on a multivariate Kaplan-Meier estimator, is proposed. The asymptotic normality and an estimator of asymptotic variance of this estimator are obtained. In the second topic, a non-parametric cure rate estimator in the presence of covariates is constructed via kernel smoothing. The asymptotic normality of this estimator is obtained, and the optimal choice of the bandwidth via cross-validation is discussed. In the third topic of this thesis, we develop a test for the presence of immunes, i.e., we test if the cure rate is zero against the alternative that it is positive, under univariate random censoring. The limiting distribution of the test statistic under the null hypothesis is obtained using extreme-value theory. Theoretical results are supported by simulation studies

Trace elements can influence the physical properties of tooth enamel

In previous studies, we showed that the size of apatite nanocrystals in tooth enamel can influence its physical properties. This important discovery raised a new question; which factors are regulating the size of these nanocrystals? Trace elements can affect crystallographic properties of synthetic apatite, therefore this study was designed to investigate how trace elements influence enamel’s crystallographic properties and ultimately its physical properties. The concentration of trace elements in tooth enamel was determined for 38 extracted human teeth using inductively coupled plasma-optical emission spectroscopy (ICP-OES). The following trace elements were detected: Al, K, Mg, S, Na, Zn, Si, B, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Sb, Se and Ti. Simple and stepwise multiple regression was used to identify the correlations between trace elements concentration in enamel and its crystallographic structure, hardness, resistance to crack propagation, shade lightness and carbonate content. The presence of some trace elements in enamel was correlated with the size (Pb, Ti, Mn) and lattice parameters (Se, Cr, Ni) of apatite nanocrystals. Some trace elements such as Ti was significantly correlated with tooth crystallographic structure and consequently with hardness and shade lightness. We conclude that the presence of trace elements in enamel could influence its physical properties. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-499) contains supplementary material, which is available to authorized users

Crystal shape and composition of enamel affect its mechanical properties

Tooth enamel is a composite material, made of an organic phase (2-4% of enamel) and an inorganic phase (96-98% of enamel) that protects the tooth layers underneath (dentin and dental pulp). Tooth enamel is the hardest and one of the toughest materials in mammals. However, enamel suffers from continuous mechanical stress that might cause cracks, creating a favourable environment for bacteria growth and leading to tooth sensitivity or fracture. Also the incorporation of ions in tooth enamel structure can affect the crystallographic, mechanical and physical properties. This study was designed to find out the relative contribution of tooth enamel's crystallography, physical and chemical characteristics to its resistance to crack propagation. The possible contribution of tooth enamel trace elemental composition on its crystallography, chemical and physical properties was investigated, as well. Extracted sound teeth were gathered from patients attending McGill Undergraduate Dental Clinic. Tooth enamel's crack length, hardness, crystallography (i.e. crystallite size, unit cell parameters of the crystal; a and c), chemical composition, tooth shade and trace elements were obtained by Scanning Electron Microscope, Vickers microhardness, X-Ray Diffraction, Fourier transform infrared spectroscopy, shade spectrophotometry and inductively-coupled plasma mass spectrometry. The statistical significance was set at P <0.05. In this study, I found that the average crack length and average length of cracks perpendicular to dentin-enamel junction that emanated from indentations induced on enamel were correlated to enamel's crystallite dimensions along c-axis. According to this finding, I proposed a new model based on Hall-Petch theory that accurately predicts crack propagation in enamel. The concentration of Ti in tooth enamel was positively associated with enamel's hardness, lightness and crystallite size along c-axis. Also, I found that the presence of Fe was associated with the formation of carbonate type A, while the concentration of Co and Ni were correlated with the formation of carbonate type B. Se substitution in tooth enamel was positively associated with unit cell parameters along a and c, on the other hand Cr and Ni had a negative correlation with unit cell parameters along c. It was shown that the presence of Pb, Ti and Mn had an association with tooth enamel's crystallite size along c-axis.Our findings show why older people suffer from tooth fracture more often than younger ones, and how the nanostructure of enamel prevents catastrophic mechanical failure. Also this study shows how the presence of trace elements can affect the physical-chemical properties of tooth enamel.L'émail dentaire est un matériau composite, constitué d'une partie organique (2-4% de l'émail) et d'une partie inorganique (96-98% de l'émail) qui protègent les couches profondes de la dent (dentine et la pulpe dentaire). L'émail dentaire est le tissu le plus dur chez les mammifères, et l'un des plus résistants. Cependant, l'émail est continuellement exposé à une agression d'origine mécanique, qui pourrait le fissurer, créant un environnement favorable à la croissance des bactéries qui pourraient provoquer la sensibilité dentaire ou la fracture de la dent. Aussi, l'incorporation des ions dans la structure de l'émail dentaire peut affecter les propriétés cristallographiques, mécaniques et physiques de ce tissu dentaire important. L'objectif de cette étude est de découvrir la relation entre la cristallographie, les propriétés physiques et chimiques de l'émail dentaire et sa résistance contre la propagation de fractures. La contribution possible des traces d'oligo-éléments dans la structure de l'émail, avec ses aspects cristallographiques et ses propriétés chimiques et physiques, a aussi été examinée. Des dents adultes ont été extraites dans la clinique dentaire d'étudiants de premier cycle de l'Université McGill. La longueur de fissure de l'émail, la dureté, la cristallographie (i.e., la taille des cristaux, la structure cristalline; le long des axes a et c), la composition chimique, la teinte et les traces des oligo-éléments ont été obtenues par microscope électronique à balayage, microdureté de Vickers, spectroscopie infrarouge à transformation de Fourier, ombre spectrophotométrie et de spectrométrie de masse à plasma inductif. Le niveau de signification statistique a été déterminé pour une valeur de P <0.05. Dans cette étude, nous avons remarqué que la longueur moyenne de la fissure et la longueur moyenne des fissures perpendiculaires à la jonction émail-dentine, émanent des indentations induites sur l'émail, ont été corrélés aux dimensions de cristal de l'émail le long de l'axe c. Selon ce rapport, nous avons proposé un nouveau modèle basé sur la théorie de Hall-Petch, qui prédit avec précision la propagation des fissures dans l'émail. La concentration de Ti dans l'émail des dents semble positivement associée à la dureté de l'émail, à la légèreté et à la taille des cristaux le long de l'axe c. En outre, nous avons constaté que la présence de Fe est associée à la formation de carbonate de type A, tandis que la concentration de Co et Ni montre une corrélation avec la formation de Type B. Cette substitution dans l'émail des dents est associée avec des paramètres de réseau cellulaire le long des axes a et c. D'autre part, Cr et Ni montent une corrélation négative avec les paramètres de la maille de cellules le long de l'axe c. La présence de Pb, Ti et Mn a un lien avec la taille des cristaux de l'émail des dents le long de l'axe c.Nos résultats montrent pourquoi les personnes âgées souffrent d'une fracture de la dent plus souvent que les plus jeunes, et comment la nanostructure de l'émail empêche une défaillance mécanique catastrophique. De plus, cette étude montre comment la présence d'oligo-éléments peut affecter les propriétés physico-chimiques de l'émail des dents

Comparison of Canine Overlap in Pediatric Patients Requiring Stainless Steel Crown Placement under General Anesthesia before and after the Procedure

Objectives: Despite the increasing popularity of pediatric dental treatments under general anesthesia, information is scarce regarding occlusal changes in patients that receive stainless steel crowns (SSCs) under general anesthesia. This study sought to compare canine overlap before and after general anesthesia in children who received SSCs under general anesthesia. In case of change, the possibility of return to the preoperative state and time required for this process were also evaluated. Materials and Methods:  This interventional before and after study was performed on 60 children between 2 to 7 years requiring dental treatment under general anesthesia. The contact point of the most prominent area of the maxillary primary canine and mandibular primary canine was marked before and immediately after general anesthesia and one and two weeks later. The change in canine overlap was analyzed using repeated measures ANOVA and linear regression test. Results: Canine overlap significantly decreased immediately after general anesthesia (P<0.05). The mean magnitude of bite opening was 0.51±0.22 mm at the site of right canine and 0.50±0.185 mm at the site of left canine. These values returned to their normal preoperative state after one week (P<0.05). Repeated measures ANOVA showed significant differences in this respect between time points (P=0.002). Conclusions: Occlusion and vertical dimension of pediatric patients may change following dental treatment under general anesthesia; the magnitude of change in canine overlap may vary depending on the class of occlusion and number of SSCs placed. These changes are temporary and often resolve within a week

High levels of A2AR and endogenous cAMP in CD4+ T cells from HIV infected patients and lack of IL-2 production

<p>. (A) CD45RA+ and CD45RA− CD4+ T cells were purified from the blood of ART-naive HIV-infected patients (n = 5) and healthy controls (n = 5). A2AR mRNA expression was assessed using qPCR. Horizontal lines correspond to the mean for each data set. (B) CD4+ T cells were purified from the blood of ART-naive HIV-infected patients (n = 6) and healthy controls (n = 8). Intra-cellular cAMP is measured using the cAMP direct enzyme immunoassay from GE healthcare Biosciences. (C) Purified naive CD4+ T cells form HIV+ART- patients and healthy controls were stimulated with high doses of anti-CD3/CD28 mAbs (5 µg/ml) during 6H and IL-2 mRNA levels were quantified by RT-PCR. (D) The epigenetic changes on methylation of the unique essential CpG site of <i>il-2</i> gene promoter in naïve CD4+ T cells from HIV+ART- patients <i>vs.</i> healthy controls following anti-CD3/CD28 mAbs activation. To reach the technical limitation due to the low frequency of naïve CD4+ T cells in HIV+ART- patients, the Clonal analysis was performed on a pool of the extracted DNA from naïve CD4 T cells of HIV+ patients and healthy controls before and after CD3/CD28 mAbs activation. *P<0.05, **P<0.01.</p