No description available.

This thesis deals with the design and implementation of a processor simulation memory subsystem. The memory subsystem is designed using the Transaction Level Modeling approach. The implementation is done in C++ language utilizing the SystemC library. The processor simulation is adopted from the Codasip company simulator. The objective is to create a functional connection between the processor and the memory inside the simulator. This connection supports communication protocols of AHB3-lite, AXI4-lite, CPB, and CPB-lite buses. The new implementation of the aforementioned connection and the memory is integrated into the original simulator. The resulting simulator is tested using unit tests.

One hundred billion tons of mine solid waste are estimated to be produced worldwide each year. In Canada, the mining and oil industries produce the most solid and semi-solid waste in the country, with more than a billion tons each year. In the earlier days of mining, the initial practices that were used to contain these waste materials consisted of surface storage, river dumping or just simple abandonment, while the more recent practices include dam impoundment and underground waste fill. These methods however can potentially cause environmental hazards and geotechnical problems. Against this context and as a result of stricter environmental regulations, cemented paste backfilling has been developed as a solution. This relatively new technology uses the produced waste tailings to backfill the mine stopes, greatly reducing their environmental impact while offering proper structural support in an efficient manner. However, the cost of cemented paste backfill (CPB) is greatly impacted by the binder content which can constitute up to 75% of its total cost. Additionally, the binder is usually mostly composed of ordinary Portland cement, and its production is highly energy-intensive and generates a large volume of carbon dioxide (CO₂). Indeed, it is estimated that the cement industry accounts for approximately 7% of the global anthropogenic CO₂ emissions, which is expected to increase on an annual basis. All of these factors have compelled the mining industry to seek alternatives for cement to enhance CPB strength, in hopes of reducing its carbon footprint. Against this context, this study investigates the effect of the addition of nanoparticles, namely nano silica (SiO₂) and nano-calcium carbonate (CaCO₃), on the strength development of CPB cured at a constant room temperature and in non-isothermal conditions. Nanoparticles have been studied and used as chemical admixtures in different cementitious materials with promising results; non-isothermal curing conditions better reflect the in-situ thermal curing conditions of CPB. Thus, numerous different laboratory tests and analyses, including uniaxial compressive strength (UCS), scanning electron microscopy (SEM) and mercury intrusion porosimetry (MIP) tests, thermogravimetric/derivative thermogravimetric (TG/DTG) analyses and electrical conductivity monitoring, have been conducted on CPB samples with or without nanoparticles, and cured at room temperatures or under non-isothermal conditions. The non-isothermal conditions replicate the development of temperature in two different sizes of CPB structures in the field. The results show that CPB that contains nanoparticles show a higher UCS over the entire period of curing in all of the tested conditions. The mechanical performance is further enhanced when tested under higher temperatures in non-isothermal temperature profiles. Most of the strength increase takes place at the early ages (3 days) of the testing. The reason for the improvement in the mechanical strength is linked to accelerated binder hydration and the nucleating and filler effects of the nano-material, which is corroborated by results obtained through microstructural analyses and EC monitoring. The use of natural gold tailings affects the mechanical performance of CPB and the accelerating effect of the nanoparticles due to sulphate attacks. Overall, these promising findings can help to contribute to reducing the carbon footprint of mining activities, and improve the efficiency and cost-effectiveness of mine backfilling processes.

The main result of underground mining extraction is creating of large underground voids (mine stopes). These empty openings are typically backfilled with an engineering cementitious material called cemented paste backfill (CPB). The main purpose of CPB application in underground mining is to provide stability and ensure the safety of underground openings, maximize ore recovery, and also provide an environmental-friendly means of underground disposal of potential acid generating tailings. CPB is a mixture of mine tailings, cement binder and water. CPB has a complex geotechnical behaviour when poured into mine voids. This is because of the different thermal (T), hydraulic (H), mechanical (M) and chemical coupled processes and interactions that take place in CPB soon after placement. In addition to these THMC behaviours, various external factors, such as stope geometry, drainage condition and arching effects add more complexity to its behaviour. In order to acquire a full understanding of CPB behaviour, there is a need to consider all of these THMC factors and processes together. So far, there has not been any study that addresses this research need. Indeed, fundamental knowledge of the THMC behaviour of CPB provides a key means for designing safe and cost-effective backfill structures, as well as optimizing mining cycles and productivity of mines. Innovative experimental tools and CPB testing methods have been developed and adopted in this research to fulfill the objectives of this research. In the first phase of the study, experiments with high columns are developed to study the THMC behaviour of CPB from early to advanced ages with respect to height of the column and curing time. The column experiments simulate the mine stope and filling sequence and provide an opportunity to study external factors, such as evaporation, on the THMC behaviour of CPB. However, an important factor is the overburden pressure from the stress due to self-weight that cannot be simulated through column experiments. Therefore, in the second phase of this study, a novel THMC curing under stress apparatus is developed to study the THMC behaviour of CPB under various pressures due to the self-weight of the CPB, drainage conditions, and filling rate and sequence. Comprehensive instrumentation and geotechnical testing are carried out to obtain fundamental knowledge on the THMC behaviour of CPB in different curing conditions from early to advanced ages. The results of these studies show that the THMC properties of CPB are coupled. Important parameters, such as curing stress, self-desiccation due to cement hydration, temperature, pore water chemistry, and mineralogical and chemical properties of the tailings, have significant influence on the shear strength and compressive strength development of CPB. Factors such as evaporation and drying iii shrinkage can also affect the hydro-mechanical properties of CPB. The curing conditions (such as curing stress, drainage and filling rate) also has significant impact on CPB behaviour and performance. The THMC interactions and the degree of influence of each factor should be included in designing backfill structures and planning mining cycles. This innovative curing under stress technique can be replaced the conventional curing of CPB (curing under zero stress and no THMC loadings), in order to optimize CPB mechanical strength assessment, increase mine safety and enhance the productivity.

Cemented paste backfill (CPB) is a novel technology developed in the past few decades to better manage mining wastes (such as tailings) in environmentally friendly way. It has received prominent interest in the mining industry around the world. In this technology, up to 60% of the total amount of tailings is reused and converted into cemented construction material that can be used for secondary support in underground mine openings (stopes) and to maximize the recovery of ore from pillars. CPB is an engineered mixture of tailings, water, and hydraulic binder (such as cement), that is mixed in the paste plant and delivered into the mine stopes either by gravity or pumping. During and after placing it into the mine stopes, the performance of CPB mainly depends on the role of the hydraulic binder, which increases the mechanical strength of the mixture through the process of cement hydration. Similar to other fine-grained soils undergoing cementations, CPB’s behavior is affected by several conditions or factors, such as cement hydration progress (curing time), chemistry of pore water, mixing and curing temperature, and filling strategy. Also, it has been found that fresh CPB placed in the mine stopes can be susceptible to many geotechnical issues, such as liquefaction under ground shaking conditions. Liquefaction-induced failure of CPB structure may cause injuries and fatalities, as well as significant environmental and economic damages. Many researches studied the effect of the aforementioned conditions on the static mechanical behavior of CPB. Other researches have evaluated the liquefaction behavior of natural soils and tailings (without cement) during cyclic loadings using shaking table test technique. Only few studies investigated the CPB liquefaction during dynamic loading events using the triaxial tests. Yet, there are currently no studies that addressed the liquefaction behavior of CPB under the previous conditions by using the shaking table technique. In this Ph.D. study, a series of shaking table tests were conducted on fresh CPB samples (75 cm × 75 cm ×70 cm), which were mixed and poured into a flexible laminar shear box (that was designed and build for the purpose of this research). Some of these shaking table tests were performed at different maturity ages of 2.5 hrs, 4.0 hrs, and 10.0 hrs, to investigate the effect of cement hydration progress on the liquefaction potential of CPB. Another set of tests were conducted to assess the effect of the chemistry (sulphate content) of the pore-water on the cyclic response of fresh CPB by exposing cyclic loads on couple of CPB models that contain different concertation of sulphate ions of 0.0 ppm and 5000 ppm. Moreover, as part of this study, series of shaking table test was conducted on CPB samples that were prepared and cured at different temperatures of 20oC and 35oC, to evaluate the effect of temperature of the cyclic behavior of CPB. Furthermore, the effect of filling strategy on the cyclic behavior of fresh CPB was assessed by conducting set of shaking tables tests on CPB models that were prepared at different filling strategies of continuous filling, and sequential or discontinuous (layered) filling. The results obtained show that CPB has different cyclic behavior and performance under these different conditions. It is observed that the progress of cement hydration (longer curing time) enhances the liquefaction resistance of CPB, while the presence of sulphate ions diminishes it. It is also found that CPB mixed and cured in low temperature is more prone to liquefaction than those prepared at higher temperatures. Moreover, the obtained results show that adopting the discontinuous (layered) filling strategy will improve the liquefaction resistance of CPB. The finding presented in this thesis will contribute to efficient, cost effective and safer design of CPB structures in the mine areas, and will help in minimizing the risks of liquefaction-induced failure of CPB structures.

Background: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction characterized by a lowered platelet count (50% from baseline) 4-10 days after heparin exposure. Autoantibodies specific for platelet factor 4 (PF4) bind PF4 and heparin complexes (PF4/H) and activate platelets through the FcgammaRIIA receptor. Severe cases of HIT can result in thrombotic complications including deep vein thrombosis, pulmonary embolism, and death. Pathogenic class-switched antibodies against PF4/H (IgG) are detectable in circulation as early as five days post-heparin exposure and peak at 14 days. The timeline and class of antibody found in HIT patients suggest that there must be pre-existing immunity against PF4/H. Thus, B cells producing anti-PF4/H antibodies must exist prior to heparin exposure. Cardiac surgery patients are disproportionately prone to anti-PF4/H seroconversion (up to 70%) and thus are utilized in this study as a model patient group. Research objective: The objective of this study is to determine whether the preoperative immune profile is associated with postoperative anti-PF4/H antibody production in a cohort of patients undergoing cardiac pulmonary bypass (CPB) surgery. Materials and methods: To characterize the preoperative immune profile, we used 1) a peripheral blood mononuclear cell (PBMC) enzyme linked immunospot (ELISPOT) assay to measure the prevalence of preoperative anti-PF4/H specific antibody secreting cells (ASC) and 2) a PF4/H-dependant enzyme immunoassay (EIA) to measure the anti-PF4/H antibodies produced by PBMCs in vitro. To characterize postoperative anti-PF4/H seroconversion in CPB patients, we used a PF4/H dependent EIA to measure in vivo levels of anti-PF4/H antibodies produced postoperatively. We also utilize a functional assay, 14C-serotonin release assay (SRA) to determine if seroconverting patients produced platelet activating antibody. Results: All patients were able to produce anti-PF4/H spots in the ELISPOT; however, this did not correlate with the titer of antibody production in vitro nor did it correlate with antibody production in the postoperative period. Instead, we found that pre-operative in vitro anti-PF4/H IgM production was associated with post-operative IgG anti-PF4/H seroconversion (Spearman’s r=0.39, P=0.018). We observed that 92.1% of CPB patients produced PF4/H antibody at postoperative week 3 with some combination of IgA, IgG, and IgM. Of the anti-PF4/H seropositive patients, 26% developed platelet activating antibody and were found seropositive when the SRA was supplemented with PF4 instead of heparin, while 15.7% were seropositive in the original SRA. It was noted that 4 of 10 patients that caused the most robust platelet activation were also seropositive for anti-PF4/H IgA antibody. Lastly, throughout this serosurveillance study, several patients that demonstrated unique immunological features are presented in this study as case studies. Specifically, we report the preoperative, surgical, clinical and postoperative characteristics for 3 patients of interest: 1) in a preoperative setting, a CPB patient’s PBMC were able to be activated and produce anti-PF4/H IgG antibody in vitro, 2) the second patient had platelet-activating antibodies in circulation prior to intraoperative heparin challenge and early post-surgery 3) the third patient who developed probable HIT. Conclusions: Based on our findings, we conclude that preoperative PF4/H ELISPOTs were unable to predict post-operative production of anti PF4/H antibodies. However, preoperative in vitro production of anti-PF4/H IgM may be associated with postoperative production of anti-PF4/IgG antibody and should be investigated further as this may help to elucidate the mechanisms for anti-PF4/H production related to HIT. / Thesis / Master of Science (MSc)

Over the past decades, cemented paste backfill (CPB) has become a common, environmentally friendly method of managing mine wastes (such as tailings). This technology allows up to 60% of the total amount of tailings to be reused and filled in the mine stopes after converting them into cemented material. Beside reducing the environmental risks associated with the traditional disposal of these materials, turning them into cemented material and placing them in the underground mine stopes can also provide secondary support for these stopes in addition to minimizing the risk of ground subsidence in the mine area. CPB is an engineered mixture of tailings, water, and hydraulic binder (such as cement, blast furnace slag, and fly ash) that is mixed in the paste plant and delivered into the mine stopes through a gravity or pumping based transportation system. During the transportation of CPB through the delivery system pipelines, the flowability of CPB depends on the rheology of the transported CPB, which is affected by different factors, such as the transportation time, temperature variation, binder type, and chemical composition of these mixtures. In addition, the performance of CPB, after placing the CPB mixture into the mine stopes, is mainly dependent on the role of the hydraulic binder, as it increases the mechanical strength of the mixture through the process of cement hydration. The mechanical strength is also influenced by different factors, such as time progress, temperature variation, and presence of chemical additives. It has previously been found that fresh CPB transported and/or placed in the mine stopes can be susceptible to temperature variation of different sources, such as the climatic effects, heat generated from the surrounding rocks, and heat generated during the process of cement hydration. Unsuitable flowability of CPB through the delivery system might lead to significant financial losses due to clogging of pipelines with unexpected hardening of CPB during transportation, which will cause delay in work and possible damages to the pipelines. Also, failure of CPB structure in the mine stopes due to inappropriate mechanical strength may cause casualties to the mine workers as well as significant environmental and economic damages. Many researchers studied the rheological properties and/or strength development of CPB under the individual effect of any of the aforementioned factors. Additionally, many researchers have evaluated the coupled effect of some of these factors on the rheology and mechanical strength of CPB material. Hitherto, there are currently no studies that addressed the combined effect of all these conditions on the rheological properties and strength development of CPB. At the first stage of this M.A.Sc. study, a series of experimental tests was conducted on fresh CPB in order to determine the combined effect of time, temperature, binder content, and chemical additives on the rheological properties of CPB. These experiments include rheological properties test (yield stress and viscosity), microstructural analysis (thermal analysis and XRD), chemical analysis (pH and Zeta potential), and monitoring tests (electrical conductivity), which were conducted on 125 CPB samples that were mixed and prepared at different temperatures (2oC, 20oC, 35oC) and cured for different curing time (0 hrs., 0.25 hrs., 1 hr., 2hrs, and 4 hrs.). These samples were prepared with different blends of hydraulic binders (PCI, PCI/Slag, and PCI/FA) and contained different dosages of sodium silicate (0%, 0.1%, 0.3%, and 0.5%). The results obtained show that rheology of CPB increases with the progress of curing time. It also increases with the increase in the initial (mixing and curing) temperature and content of sodium silicate. It was also found that the partial usage of slag and FA reduces the rheological properties. However, CPBs containing PCI/FA as binder have lower rheological properties, and thus better flowability, than those that contain PCI/Slag as binder. At the second stage of this M.A.Sc. study, in order to understand the combined effect of time, temperature and sodium silicate content on the strength development of slag-CPB, unconfined compression (UCS) test, microstructural analysis (thermal analysis and MIP), and monitoring tests (electrical conductivity, suction, and volumetric water content) were conducted on 72 CPB samples that were prepared with PCI-Slag as a binder, cured for different times (1 day, 3 days, 7 days, and 28 days) under different curing temperatures of (2oC, 20oC, 35oC), and contained different dosages of sodium silicate (0%, 0.3% and 0.5%). The results obtained at this stage showed that the strength development of slag-CPB increases with the progress of curing time and temperature. It also increases with the increase in the sodium silicate content. Also, the combined effect of high temperature, high dosage of sodium silicate and longer curing time showed significant enhancement in the mechanical strength of slag-CPB. The findings of this M.A.Sc. research will contribute to cost effective, efficient, and safer design of CPB structures in the mine areas. It will also help in minimizing financial loss associated with unsuitable flowability of CPB transported in the CPB delivery system besides reducing the risks of human loss, and the environmental and economic damages associated with the failure of CPB structures.

INTRODUCTION : L’utilisation de la circulation extracorporelle durant la chirurgie cardiaque est associée à des problèmes pulmonaires chez certains patients. L’utilisation d’une pression pulsatile induite par un ballon intra-aortique (BIA) pourrait diminuer la dysfonction endothéliale et la survenue de tels événements. MATÉRIEL ET MÉTHODE : 12 porcs Landrace-Yorkshire ont subi une circulation extracorporelle et ont été divisés en deux groupes et 4 porcs ont servi de contrôles sans CEC. Le premier groupe (n=6) a bénéficié d’un flot pulsatile créé par un BIA en mode interne à 80 battements par minute durant les 90 minutes de l’opération alors que le second groupe (n=6) a subi une CEC standard. Après 60 minutes de reperfusion suivant la CEC, les valeurs hémodynamiques ont été évaluées dont les pressions artérielles, les pressions pulmonaires, l’index cardiaque et la concentration de glucose et de lactate. Les artères pulmonaires sont ensuite montées en chambre d’organe pour évaluer la fonction endothéliale. RÉSULTATS : Les porcs avec pression pulsatile ont tendance à produire moins de lactate sanguin après 60 minutes de reperfusion. Les autres valeurs hémodynamiques sont semblables. Finalement, la relaxation à la bradykinine est significativement meilleure dans le groupe pression pulsatile alors que la relaxation à l’acétylcholine n’est pas significativement différente. CONCLUSION : Ces résultats démontrent que la perfusion pulsatile produite par un BIA protège l’endothélium pulmonaire lors d'une CEC. Cet effet pourrait être dû à une augmentation du flot bronchique qui diminuerait l’ischémie pulmonaire ou à une diminution de la libération de cytokines et de bradykinine qui réduirait les dommages de reperfusion. / INTRODUCTION : Cardiopulmonary bypass (CPB) during cardiac surgery leads to postoperative pulmonary complications. The use of pulsatile pressure with an intra-aortic balloon pump (IABP) could preserve the endothelial function and decrease the occurence of pulmonary problems. MATERIAL AND METHODS : Twelve Landrace-Yorkshire swine were divided into two groups, one group (n=6) received pulsatile perfusion under CPB from an IABP in an internal mode at 80 beats per minute (bpm) and the other (n=6) had a standard CPB of 90 minutes. A third group (n=4) has been used as controls without CPB. The two first groups underwent aortic clamping for 80 minutes with administration of intermittent blood cardioplegia. After 60 minutes of reperfusion following of bypass, swine were sacrificed and pulmonary arteries were harvested. Haemodynamic values were calculated including pulmonary arterial pressures (PAP), mean arterial pressures (mAP), lactate production, blood glucose and cardiac index. Pulmonary arteries were placed in organ chambers and vascular reactivity studies were performed. RESULTS : There was a trend towards lower lactate production with use of pulsatile perfusion after 60 minutes of reperfusion. All other hemodynamics were not significally different in both groups. Relaxation to bradykinin was greater in pulsatile group while relaxation to acetylcholine did not differ. CONCLUSION : IABP induced pulsatile pressure protect the pulmonary endothelium during CPB. This could be explained by an increase in blood flow through the bronchial arteries or by a decreased release of cytokines or bradykinin which could reduce reperfusion damage.

INTRODUÇÃO: A Síndrome de Rubinstein-Taybi (RTS) é uma doença genética rara, caracterizada por dismorfismos craniofaciais típicos, polegares e háluces alargados, deficiência mental e baixa estatura. A incidência estimada é de 1: 125 000 a 1: 330000 nativivos. A SRT geralmente ocorre esporadicamente, mas pode ser herdada com um padrão de herança autossômico dominante. O diagnóstico da SRT é essencialmente clínico. OBJETIVOS: Realizar o estudo genético-clínico e citogenético em 30 pacientes brasileiros com SRT, e descrever de forma sistematizada a freqüência de dismorfismos faciais e malformações múltiplas encontradas. MÉTODOS: Neste estudo observacional retrospectivo e prospectivo, os pacientes foram seguidos no período de agosto de 2005 a junho de 2009. O cariótipo com bandeamento G foi realizado em todos os pacientes. RESULTADOS: A maioria dos pacientes avaliados foi do sexo feminino (60%). As seguintes características foram observadas em todos os pacientes da nossa casuística: atraso de desenvolvimento neuropsicomotor, ponta nasal voltada para baixo, columela proeminente, sorriso característico, dificuldades alimentares na infância, persistência dos coxins fetais, falanges distais dos polegares alargadas e pés planos. A baixa estatura e a microcefalia foi observada em 80% e 76% dos casos, respectivamente. As principais características craniofaciais observadas foram: fronte proeminente (86%), ponte nasal larga (60%), hipertelorismo (70%), sobrancelhas espessas e arqueadas (96%) cílios longos em 93%, prega epicântica (76%), fissura palpebral infra vertidas (76%), abertura bucal estreita (93%), retrognatismo (76 %), sorriso característico em 100%, palato alto e estreito (93%), anomalias dentárias (83%). Outras anomalias identificadas foram: estrabismo, erros de refração, obstrução do canal lacrimal, háluces e polegares alargados, angulação de polegares, anomalias do pavilhão auricular (rotação/posição/tamanho/forma), angulação do hálux, clinodactilia, sobreposição dos pododáctilos, falanges distais alargadas de outros dedos, marcha rígida, hipotonia, sopro cardíaco, cardiopatia congênita, criptoquidia, hemangioma plano e hipertricose. Uma paciente apresentou translocação recíproca de novo 46, XX, t (2; 16)(q36.3; p13.3). CONCLUSÕES: A raridade da SRT e o amplo espectro das manifestações clínicas pode atrasar o diagnóstico clínico. A média da idade ao diagnóstico dos nossos pacientes com SRT foi de três anos e oito meses. Todas as crianças devem receber avaliação por geneticista pediátrico, cardiologista, oftalmologista, neuropediatra, e odontopediatra / INTRODUCTION: Rubinstein-Taybi syndrome (RTS) is a rare genetic disorder characterized by distinctive craniofacial dysmorphisms, broad thumbs and toes and mental and statural deficiency. The prevalence of RTS has been estimated to be 1 in 125000 to 1: 330000 live births. RTS usually occurs sporadically although it can be inherited as an autosomal dominant disorder. The diagnosis of RTS is primarily based on clinical features. OBJECTIVES: We performed a clinical and cytogenetic assay in a group of 30 Brazilian RTS patients. We also decribed the frequencies of facial dysmorphisms and multiple malformations. METHODS: In this observational retrospective and prospective study, the patients were followed from August 2005 to June 2009. Chromosomal analysis was performed by G-banding karyotype. RESULTS: Most of the patients were female (60%).The following abnormalities were present in all of the patients: delayed psychomotor development, beaked nose, proeminent collumel, typical facies, broad thumbs and toes, flat feet, joint laxity, feeding problems during the childhood, and finger pads. Short stature was present in 80%, and microcephalia in 76% of the cases, respectively. Main craniofacial characteristics are frontal bossing (86%), wide nasal bridge (60%), ocular hyperthelorism (70%), high arched eyebrows (96%), long eyelashes (93%), epicathal folds (76%), downslanting palpebral fissures (76%), small opening of the mouth (93%), retrognathism (76%), grimacing smile (100%), high arched palate (93%), and dental anomalies (83%). Other findings were: strabism, refractive error, lacrimal obstruction, wide thumb and halux, angulated thumbs, external ears anomalies (rotation, implantation and morfology), angulated halux, clinodactyly, crowded toes, broad distal falanges of other fingers, stiff gait, hipotonia, cardiac murmur, congenital heart defect, undescendent testis, hypertrichosis, and hemangioma. One female patient has found to have a reciprocal de novo translocation t(2;16)(q36.3;p13.3) on G-banding karyotype CONCLUSIONS: The rarity of RTS and the wide spectrum of clinical manifestations, may delay the clinical diagnosis of RTS. The average age at the diagnosis of our patients was 3 years and 8 months. All children of RTS should receive an evaluation by a pediatric geneticist, cardiologist, ophthalmologist, pediatric neurologist, and pediatric dentist

INTRODUÇÃO: A Síndrome de Rubinstein-Taybi (RTS) é uma doença genética rara, caracterizada por dismorfismos craniofaciais típicos, polegares e háluces alargados, deficiência mental e baixa estatura. A incidência estimada é de 1: 125 000 a 1: 330000 nativivos. A SRT geralmente ocorre esporadicamente, mas pode ser herdada com um padrão de herança autossômico dominante. O diagnóstico da SRT é essencialmente clínico. OBJETIVOS: Realizar o estudo genético-clínico e citogenético em 30 pacientes brasileiros com SRT, e descrever de forma sistematizada a freqüência de dismorfismos faciais e malformações múltiplas encontradas. MÉTODOS: Neste estudo observacional retrospectivo e prospectivo, os pacientes foram seguidos no período de agosto de 2005 a junho de 2009. O cariótipo com bandeamento G foi realizado em todos os pacientes. RESULTADOS: A maioria dos pacientes avaliados foi do sexo feminino (60%). As seguintes características foram observadas em todos os pacientes da nossa casuística: atraso de desenvolvimento neuropsicomotor, ponta nasal voltada para baixo, columela proeminente, sorriso característico, dificuldades alimentares na infância, persistência dos coxins fetais, falanges distais dos polegares alargadas e pés planos. A baixa estatura e a microcefalia foi observada em 80% e 76% dos casos, respectivamente. As principais características craniofaciais observadas foram: fronte proeminente (86%), ponte nasal larga (60%), hipertelorismo (70%), sobrancelhas espessas e arqueadas (96%) cílios longos em 93%, prega epicântica (76%), fissura palpebral infra vertidas (76%), abertura bucal estreita (93%), retrognatismo (76 %), sorriso característico em 100%, palato alto e estreito (93%), anomalias dentárias (83%). Outras anomalias identificadas foram: estrabismo, erros de refração, obstrução do canal lacrimal, háluces e polegares alargados, angulação de polegares, anomalias do pavilhão auricular (rotação/posição/tamanho/forma), angulação do hálux, clinodactilia, sobreposição dos pododáctilos, falanges distais alargadas de outros dedos, marcha rígida, hipotonia, sopro cardíaco, cardiopatia congênita, criptoquidia, hemangioma plano e hipertricose. Uma paciente apresentou translocação recíproca de novo 46, XX, t (2; 16)(q36.3; p13.3). CONCLUSÕES: A raridade da SRT e o amplo espectro das manifestações clínicas pode atrasar o diagnóstico clínico. A média da idade ao diagnóstico dos nossos pacientes com SRT foi de três anos e oito meses. Todas as crianças devem receber avaliação por geneticista pediátrico, cardiologista, oftalmologista, neuropediatra, e odontopediatra / INTRODUCTION: Rubinstein-Taybi syndrome (RTS) is a rare genetic disorder characterized by distinctive craniofacial dysmorphisms, broad thumbs and toes and mental and statural deficiency. The prevalence of RTS has been estimated to be 1 in 125000 to 1: 330000 live births. RTS usually occurs sporadically although it can be inherited as an autosomal dominant disorder. The diagnosis of RTS is primarily based on clinical features. OBJECTIVES: We performed a clinical and cytogenetic assay in a group of 30 Brazilian RTS patients. We also decribed the frequencies of facial dysmorphisms and multiple malformations. METHODS: In this observational retrospective and prospective study, the patients were followed from August 2005 to June 2009. Chromosomal analysis was performed by G-banding karyotype. RESULTS: Most of the patients were female (60%).The following abnormalities were present in all of the patients: delayed psychomotor development, beaked nose, proeminent collumel, typical facies, broad thumbs and toes, flat feet, joint laxity, feeding problems during the childhood, and finger pads. Short stature was present in 80%, and microcephalia in 76% of the cases, respectively. Main craniofacial characteristics are frontal bossing (86%), wide nasal bridge (60%), ocular hyperthelorism (70%), high arched eyebrows (96%), long eyelashes (93%), epicathal folds (76%), downslanting palpebral fissures (76%), small opening of the mouth (93%), retrognathism (76%), grimacing smile (100%), high arched palate (93%), and dental anomalies (83%). Other findings were: strabism, refractive error, lacrimal obstruction, wide thumb and halux, angulated thumbs, external ears anomalies (rotation, implantation and morfology), angulated halux, clinodactyly, crowded toes, broad distal falanges of other fingers, stiff gait, hipotonia, cardiac murmur, congenital heart defect, undescendent testis, hypertrichosis, and hemangioma. One female patient has found to have a reciprocal de novo translocation t(2;16)(q36.3;p13.3) on G-banding karyotype CONCLUSIONS: The rarity of RTS and the wide spectrum of clinical manifestations, may delay the clinical diagnosis of RTS. The average age at the diagnosis of our patients was 3 years and 8 months. All children of RTS should receive an evaluation by a pediatric geneticist, cardiologist, ophthalmologist, pediatric neurologist, and pediatric dentist