How is leflunomide prescribed and used in Australia? analysis of prescribing and adverse effect reporting

Purpose To evaluate the use of leflunomide in the Australian community since introduction in 2000. Trends in adverse drug reaction (ADR) reporting were also studied. Methods Annual Australian prescription and dispensing statistics were analysed. Drug utilisation was estimated as defined daily doses (DDD)/1000 inhabitants/day. ADR data from the Therapeutic Goods Administration's Adverse Drug Reactions Advisory Committee (ADRAC) national monitoring system were compared with the World Health Organisation (WHO) Vigibase records. Results Leflunomide use in Australia (dispensing data) increased from 0.2 in 2000 to 0.4 DDD/1000 inhabitants/day in 2002. The same overall pattern was observed in the 'authority to prescribe' data. From 2000-2002, prescribing of the starter pack (3 x 100 mg loading dose plus 30 x 20 mg tablets) declined (down 74%); likewise for the 20mg (30 tablets) pack. Gradual increases were noted for the 10 mg (30 tablets) pack (up 40%). Approximately 135 reports, detailing about 370 individual ADR, were generated annually. Gastro-intestinal disorders predominated, accounting for 24% of reactions reported to ADRAC. Skin and appendages disorders constituted 14% of reported reactions. Deaths in leflunomide users were attributed to a combination of haematological and gastro-intestinal complications, but it was not possible to ascertain other medication usage or contributing factors. Trends observed with the ADRAC reports were consistent with the WHO database. Conclusions Leflunomide was the first registered DMARD in Australia in over a decade and its use has increased within the community. The ADR reports might have contributed to Australian rheumatologists gradually abandoning loading patients with high doses of leflunomide in favour of starting therapy at lower doses. Copyright (c) 2006 John Wiley & Sons, Ltd.

On waveform analysis, the adaptive task technique, and the effect of vibration on manual control skill

A re-examination of fundamental concepts and a formal structuring of the waveform analysis problem is presented in Part I. eg. the nature of frequency is examined and a novel alternative to the classical methods of detection proposed and implemented which has the advantage of speed and independence from amplitude. Waveform analysis provides the link between Parts I and II. Part II is devoted to Human Factors and the Adaptive Task Technique. The Historical, Technical and Intellectual development of the technique is traced in a review which examines the evidence of its advantages relative to non-adaptive fixed task methods of training, skill assessment and man-machine optimisation. A second review examines research evidence on the effect of vibration on manual control ability. Findings are presented in terms of percentage increment or decrement in performance relative to performance without vibration in the range 0-0.6Rms'g'. Primary task performance was found to vary by as much as 90% between tasks at the same Rms'g'. Differences in task difficulty accounted for this difference. Within tasks vibration-added-difficulty accounted for the effects of vibration intensity. Secondary tasks were found to be largely insensitive to vibration except secondaries which involved fine manual adjustment of minor controls. Three experiments are reported next in which an adaptive technique was used to measure the % task difficulty added by vertical random and sinusoidal vibration to a 'Critical Compensatory Tracking task. At vibration intensities between 0 - 0.09 Rms 'g' it was found that random vibration added (24.5 x Rms'g')/7.4 x 100% to the difficulty of the control task. An equivalence relationship between Random and Sinusoidal vibration effects was established based upon added task difficulty. Waveform Analyses which were applied to the experimental data served to validate Phase Plane analysis and uncovered the development of a control and possibly a vibration isolation strategy. The submission ends with an appraisal of subjects mentioned in the thesis title.

Determinação de CD, PB, e TL em água produzida por HR-CS GF AAS após extração em ponto nuvem

Produced water is a major problem associated with the crude oil extraction activity. The monitoring of the levels of metals in the waste is constant and requires the use of sensitive analytical techniques. However, the determination of trace elements can often require a pre-concentration step. The objective of this study was to develop a simple and rapid analytical method for the extraction and pre-concentration based on extraction phenomenon cloud point for the determination of Cd, Pb and Tl in produced water samples by spectrometry of high resolution Absorption source continues and atomization graphite furnace. The Box Behnken design was used to obtain the optimal condition of extraction of analytes. The factors were evaluated: concentration of complexing agent (o,o-dietilditilfosfato ammonium, DDTP), the concentration of hydrochloric acid and concentration of surfactant (Triton X -114). The optimal condition obtained through extraction was: 0,6% m v-1 DDTP, HCl 0,3 mol L-1 and 0,2% m v-1 of Triton X - 114 for Pb; 0,7% m v-1 DDTP, HCl 0,8 mol L-1 and 0,2% m v-1 Triton X-114 for Cd. For Tl was evidenced that best extraction condition occurs with no DDTP, the extraction conditions were HCl 1,0 mol L-1 e 1,0% m v-1 de Triton X - 114. The limits of detection for the proposed method were 0,005 µg L-1 , 0,03 µg L-1 and 0,09 µg L-1 to Cd, Pb and Tl, Respectively. Enrichment factors Were greater than 10 times. The method was applied to the water produced in the Potiguar basin, and addition and recovery tests were performed, and values were between 81% and 120%. The precision was expressed with relative standard deviation (RSD) is less than 5%

Recuperação e purificação do antígeno 503 de Leishmania i. chagasi expresso em E. coli e remoção de endotoxina utilizando adsorção em leito expandido

The growing interest and applications of biotechnology products have increased the development of new processes for recovery and purification of proteins. The expanded bed adsorption (EBA) has emerged as a promising technique for this purpose. It combines into one operation the steps of clarification, concentration and purification of the target molecule. Hence, the method reduces the time and the cost of operation. In this context, this thesis aim was to evaluate the recovery and purification of 503 antigen of Leishmania i. chagasi expressed in E. coli M15 and endotoxin removal by EBA. In the first step of this study, batch experiments were carried out using two experimental designs to define the optimal adsorption and elution conditions of 503 antigen onto Streamline chelating resin. For adsorption assays, using expanded bed, it was used a column of 2.6 cm in diameter by 30.0 cm in height coupled to a peristaltic pump. In the second step of study, the removal of endotoxin during antigen recovery process was evaluated employing the non-ionic surfactant Triton X-114 in the washing step ALE. In the third step, we sought developing a mathematical model able to predict the 503 antigen breakthrough curves in expanded mode. The experimental design results to adsorption showed the pH 8.0 and the NaCl concentration of 2.4 M as the optimum adsorption condition. In the second design, the only significant factor for elution was the concentration of imidazole, which was taken at 600 mM. The adsorption isotherm of the 503 antigen showed a good fit to the Langmuir model (R = 0.98) and values for qmax (maximum adsorption capacity) and Kd (equilibrium constant) estimated were 1.95 mg/g and 0.34 mg/mL, respectively. Purification tests directly from unclarified feedstock showed a recovery of 59.2% of the target protein and a purification factor of 6.0. The addition of the non-ionic surfactant Triton X-114 to the washing step of EBA led to high levels (> 99%) of LPS removal initially present in the samples for all conditions tested. The mathematical model obtained to describe the 503 antigen breakthrough curves in Streamline Chelanting resin in expanded mode showed a good fit for both parameter estimation and validation steps. The validated model was used to optimize the efficiencies, achieving maximum values of the process and of the column efficiencies of 89.2% and 75.9%, respectively. Therefore, EBA is an efficient alternative for the recovery of the target protein and removal of endotoxin from an E. coli unclarified feedstock in just one step.

Accumulation of organic carbon in the Laptev Sea

Composition and accumulation rates of organic carbon in Holocene sediments provided data to calculate an organic carbon budget for the Laptev Sea continental margin. Mean Holocene accumulation rates in the inner Laptev Sea vary between 0.14 and 2.7 g C cm**2/ky; maximum values occur close to the Lena River delta. Seawards, the mean accumulation rates decrease from 0.43 to 0.02 g C cm**2/ky. The organic matter is predominantly of terrigenous origin. About 0.9*10**6 t/year of organic carbon are buried in the Laptev Sea, and 0.25*10**6 t/year on the continental slope. Between about 8.5 and 9 ka, major changes in supply of terrigenous and marine organic carbon occur, related to changes in coastal erosion, Siberian river discharge, and/or Atlantic water inflow along the Eurasian continental margin.

Speciation analysis of Arsenic in fish and rice samples using liquid chromatography-inductively coupled plasma mass spectrometry

Chemical speciation in foodstuffs is of uttermost importance since it is nowadays recognized that both toxicity and bioavailability of an element depend on the chemical form in which the element is present. Regarding arsenic, inorganic species are classified as carcinogenic while organic arsenic, such as arsenobetaine (AsB) or arsenocholine (AsC), is considered less toxic or even non-toxic. Coupling a High Performance Liquid Chromatographer (HPLC) with an Inductively Coupled Plasma Mass Spectrometer (ICP-MS) combines the power of separation of the first with the selectivity and sensitivity of the second. The present work aims at developing a method, using HPLC-ICP-MS technique, to identify and quantify the chemical species of arsenic present in two food matrices, rice and fish. Two extraction methods, ultrasound and microwave, and different settings were studied. The best method was chosen based on recovery percentages. To ensure that no interconversion of species was occurring, individual spikes of each species of arsenic were made in both matrices and recovery rates were calculated. To guaranty accurate results reference material BCR-627 TUNA FISH, containing certified values for AsB and DMA, was analyzed. Chromatographic separation was achieved using an anion exchange column, HAMILTON-PRP X-100, which allowed to separate the four arsenic species for which standards were available (AsB, dimethylarsenic (DMA), arsenite (AsIII), arsenate (AsV). The mobile phase was chosen based on scientific literature and adjusted to laboratory conditions. Different gradients were studied. As a result we verified that the arsenic species present in both matrices were not the same. While in fish 90% of the arsenic present was in the form of arsenobetaine, in rice 80% of arsenic was present as DMA and 20% as inorganic arsenic.

Predicción de la distorsión en anillos rolados sin costura durante tratamiento térmico de temple y revenido usando simulación numérica

La corrección de una falla por distorsión puede ser compleja ya que involucra efectos microestructurales y esfuerzos residuales que son la causa principal del fenómeno de distorsión. Las fallas por distorsión son serias debido a que pueden conducir a que el producto final no cumpla con los requerimientos dimensionales y no sea aceptado para desarrollar su función. Hoy en día, la problemática es la distorsión que sufren los componentes cuando se les somete a un tratamiento térmico temple, debido a las transformaciones de fase y esfuerzos residuales que se generan por el enfriamiento rápido, así como del tratamiento térmico de revenido donde el exceso de carbono es liberado de la estructura cristalina de la martensita y/o bainita y genera la deformación en la estructura cristalina, con esta problemática es posible hacer uso del modelo de Tratamiento Térmico que contiene el paquete comercial computacional FORGE HPC 2011®, para tratar de reproducir estos fenómenos que se llevan a cabo durante los tratamientos térmicos mencionados, y posteriormente generar información relacionada al tratamiento térmico de revenido, para desarrollar un modelo matemático que sea capaz de predecir las propiedades mecánicas finales. Este trabajo consistió en 3 etapas, la primer etapa se basó en estudiar detalladamente el grado de acero 42CrMo4 al aplicarle un tratamiento térmico de temple, bajo condiciones industriales con la finalidad de generar mayor conocimiento de los fenómenos de distorsión del acero antes mencionado, los cuales muchos autores atribuyen que este fenómeno se presenta con mayor frecuencia durante el temple, debido a la transformación de fase martensita, fase metaestable más dura en los aceros que tienen la capacidad de generar esta estructura cristalina, el experimento se desarrolló tratando térmicamente 16 anillos con las siguientes dimensiones; diámetro exterior = 2631 mm, pared = 164 mm y altura de 188 mm, instrumentados cada componente con 20 termopares tipo “k” de γ mm de diámetro, orientados cada 90°, esta metodología se desarrolló con la finalidad de obtener el máximo dato posible durante temple para posteriormente asociarlo con los coeficientes de transferencia de calor h, y así modelar la distorsión en las piezas utilizando un paquete comercial computacional, así como las condiciones de enfriamiento de la primer prueba experimental, encontrando errores máximos de 10 % comparando los resultados experimentales con los resultados obtenidos de la simulación. La segunda parte del proyecto consistió en una matriz de experimentos de tratamientos térmicos de temple y revenido, donde las variables principales fueron la temperatura y el tiempo, aplicadas en 13 probetas con las siguientes dimensiones; 100 mm X 100 mm X 200 mm, para generar conocimiento de la evolución de la dureza así como las propiedades mecánicas del mismo grado de acero, esta parte del experimento tuvo como finalidad el desarrollo y evaluación de un modelo matemático implementado en computadora que gobierne dicho comportamiento, encontrando errores en el rango de 1 hasta 40 %, comparando los resultados experimentales vs los resultados simulados. La tercera etapa del proyecto consistió en evaluar el grado de acero AISI 8630 y AISI 4340 utilizando el modelo de tratamiento térmico de revenido y datos experimentales de tres tiempos y tres temperaturas para cada uno de los aceros ya mencionados, encontrando que el modelo de tratamiento térmico de revenido no es capaz de reproducir perfiles de dureza en aceros de madia y alta aleación como están clasificados los aceros mencionados, ya que los resultados entre la parte experimental y la simulada no coincide con una línea recta para el acero AISI 8630, se encontró un coeficiente de correlación de 0.87 y errores entre 22 y 44 %, y para el acero AISI 4340, se encontró un coeficiente de correlación de 0.53 y errores entre 17 y 33 %

Estádios fenológicos e marcha de absorção de nutrientes da soja.

Estádios fenológicos: fase reprodutiva (crescimento indeterminado e determinado); fase vegetativa. Marcha de absorção de nutrientes da soja: macronutrientes (nitrogênio, cálcio, fósforo, magnésio, potássio e enxofre) e micronutrientes (Boro, manganês, cobre, zinco). Extração e exportação de macro e micronutrientes em diferentes cultivares de soja: BRS 184, SYN 1059, DM 6563 - Intacta RR2 PRO (tm).

Dinâmica de uma floresta tropical manejada na Amazônia oriental

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Tecnologia, Departamento de Engenharia Florestal, 2016.

Análise de viabilidade de injeção de fluidos alternativos ao vapor em reservatórios de óleo pesado

Many of hydrocarbon reserves existing in the world are formed by heavy oils (°API between 10 and 20). Moreover, several heavy oil fields are mature and, thus, offer great challenges for oil industry. Among the thermal methods used to recover these resources, steamflooding has been the main economically viable alternative. Latent heat carried by steam heats the reservoir, reducing oil viscosity and facilitating the production. This method has many variations and has been studied both theoretically and experimentally (in pilot projects and in full field applications). In order to increase oil recovery and reduce steam injection costs, the injection of alternative fluid has been used on three main ways: alternately, co-injected with steam and after steam injection interruption. The main objective of these injection systems is to reduce the amount of heat supplied to the reservoir, using cheaper fluids and maintaining the same oil production levels. This works discusses the use of carbon dioxide, nitrogen, methane and water as an alternative fluid to the steam. The analyzed parameters were oil recoveries and net cumulative oil productions. The reservoir simulation model corresponds to an oil reservoir of 100 m x 100 m x 28 m size, on a Cartesian coordinates system (x, y and z directions). It is a semi synthetic model with some reservoir data similar to those found in Brazilian Potiguar Basin. All studied cases were done using the simulator STARS from CMG (Computer Modelling Group, version 2009.10). It was found that waterflood after steam injection interruption achieved the highest net cumulative oil compared to other fluids injection. Moreover, it was observed that steam and alternative fluids, co-injected and alternately, did not present increase on profitability project compared with steamflooding

Prevalencia del síndrome de cementación ósea en pacientes de artroplastia de cadera, Hospital Universitario Mayor Méderi 2014

Resumen Introducción: Con el fin de estimar la prevalencia del síndrome de cementación ósea (SICO) en pacientes llevados a artroplastia de cadera cementada en el Hospital Universitario Mayor Méderi 2014. Materiales y métodos: Se realizó un estudio observacional, descriptivo, de corte transversal, se evaluaron los registros de historia clínica de los pacientes llevados a artroplastia cementada de cadera desde enero a diciembre de 2014. Se estimó la prevalencia del número total de casos de SICO sobre el total de intervenidos y la mortalidad del número de muertes intraoperatorias sobre el total de pacientes que desarrollaron el SICO. Resultados: Se encontraron 102 pacientes llevados a artroplastia cementada de cadera; 73,5% de género femenino, la mediana de edad fue 82 años, la prevalencia de SICO fue de 0,96 x 100 procedimientos y la mortalidad de 7,14 x 100 eventos (1 caso), el evento más frecuentemente relacionado fue las Perdida sanguínea < 300ml (p.valor: 0,006), el resto de diferencias entre los factores de riesgo reconocidos no fueron estadísticamente significativas. Discusión Se encontró una baja frecuencia del evento, con una muerte relacionada, se requieren estudios prospectivos para explorar desenlaces en el tiempo para la presentación de SICO y factores de riesgo adicionales. Palabras clave: "Hipotensión/Diagnóstico", "Prevalencia", "Artroplastia de Reemplazo de Cadera/Efectos Adversos", "Cementos Óseos/Efectos Adversos", "Complicaciones Postoperatorias/Etiología" y "Complicaciones Postoperatorias/Inducido Químicamente"

Agriculture and forest: A sustainable strategy in the Brazilian Amazon.

Large-scale agriculture is increasing in anthropogenically modified areas in the Amazon Basin. Crops such as soybean, maize, oil palm, and others are being introduced to supply the world demand for food and energy. However, the current challenge is to enhance the sustainability of these areas by increasing efficiency of production chains and to improve environmental services. The Amazon Basin has experienced a paradigm shift away from the traditional slash-and-burn agricultural practices, which offers decision makers the opportunity to make innovative interventions to enhance the productivity in previously degraded areas by using trees to ecological advantage. This study describes a successful experiment integrating the production of soybean and paricá (Glycine max L. and Schizolobium amazonicum) based on previous research that indicated potential topoclimatic zones for planting paricá in the Brazilian state of Pará. This paper shows that a no-tillage system reduces the effects of drought compared to conventional tillage still used by many farmers in the region. The integrated system was implemented during the 2014/2015 season in 234.6 ha in the high-potential zone in the municipality of Ulianópolis, Pará. Both soybean and paricá were planted simultaneously. Paricá was planted in 5 m x 2 m inter-tree spacing totaling 228x103 trees per hectare and soybean, in 4 m x 100 m spacing, distributed in nine rows with a 0.45 m inter-row distance, occupying 80% of the area. The harvested soybean production was 3.4 t ha-1, higher than other soybean monocultures in eastern Pará. Paricá benefited from soybean fertilization in the first year: It exhibited rapid development in height (3.26 m) and average diameter (3.85 cm). Trees and crop rotation over the following years is six years for forest species and one year for each crop. Our results confirm there are alternatives to the current production systems able to diminish negative impacts resulting from monoculture. In addition, the system provided environmental services such as reduced soil erosion and increased carbon stock by soil cover with no-tillage soybean cultivation. The soybean cover contributes to increased paricá thermal regulation and lower forestry costs. We concluded that innovative interventions are important to show local farmers that it is possible to adapt an agroforest system to large-scale production, thus changing the Amazon.

Dinâmica populacional de Tetranychus ogmophallos (Acari: Tetranychidae) em genótipos de amendoim forrageiro (Arachis spp.) no estado do Acre.

O amendoim forrageiro é uma leguminosa herbácea tropical e perene, que apresenta importância na produção de forragem em pastos consorciados com gramíneas sob sistemas pecuários intensivos. Dentre as pragas associadas ao amendoim forrageiro, o ácaro-carmim, Tetranychus ogmophallos Ferreira & Flechtmann, é uma das principais, causando injúrias pela contínua sucção de seiva. O objetivo deste trabalho foi determinar a dinâmica populacional de T. ogmophallos em dois acessos de amendoim forrageiro (Arachis pintoi e um híbrido de Arachis pintoi x Arachis appressipila) no estado do Acre. O levantamento foi realizado no período de março de 2014 a dezembro de 2015. Semanalmente, era lançado aleatoriamente, um quadrado de 100 x 100 cm, em três repetições por genótipo. Em cada lançamento eram coletadas, aleatoriamente, 20 folhas/genótipo, totalizando 60 folhas por amostragem/genótipo. Em laboratório os ácaros eram contabilizados sob microscópio estereoscópio. Os picos populacionais de T. ogmophallos foram verificados nos meses de outubro a novembro nos dois genótipos de amendoim forrageiro. Também foi observado que ataque de T. ogmophallos não causou mortalidade de plantas nos dois genótipos.

Distribuição diamétrica de uma comunidade arbórea na Floresta Estadual do Amapá, Brasil.

A distribuição dos diâmetros é uma das análises mais empregadas para retratar o comportamento estrutural de um povoamento. Assim, este estudo objetivou avaliar a estrutura diamétrica da comunidade e das principais espécies lenhosas por meio das funções de densidade probabilísticas em uma floresta de terra firme no módulo IV da Floresta Estadual do Amapá (FLOTA/AP) no Município de Calçoene/AP. Os dados de diâmetro à altura do peito (DAP) foram obtidos de um inventário realizado em uma área de 1 hectare (100 x 100 m). A estrutura diamétrica foi analisada para toda a comunidade e para as quatro principais espécies ranqueadas segundo seus índices de valor de importância. Para avaliação dos ajustes das funções: Normal, Log-normal, Gamma e Weibull 3P foi utilizado o teste de Kolmogorov-Smirnov (a = 0,05). A maioria das espécies apresentaram assimetria positiva e curtose do tipo platicúrtica, o que demonstra o padrão típico de floresta nativa em forma de "J" invertido. A função Weibull 3P e Gamma foram aderentes no teste K-S aos dados das quatro espécies analisadas, sendo a primeira a mais indicada para descrever a distribuição diamétrica de três das quatro espécies de maior IVI, e também da referida floresta de terra firme. Conclui-se, ainda, que estudos como este devem ser realizados constantemente visando introduzir e avaliar a eficiência de outras funções densidade de probabilidade para a descrição da distribuição diamétrica de povoamentos em florestas inequiâneas.

Clinico-genetic aspects of a pediatric non-neurofibromatosis type 1 malignant triton tumor with loss of chromosome X

Malignant triton tumor (MTT) is an aggressive peripheral nerve sheath tumor with rhabdomyoblastic differentiation. Less than 100 cases have been described, being mostly male children with type 1 neurofibromatosis. We report a 6-year-old female with MTT and no diagnostic criteria for neurofibromatosis type 1. Cytogenetic analysis showed a 46,X,-X[4]/46,XX[16] karyotype. She underwent a transfemoral amputation and chemotherapy and is free of disease 15 months after diagnosis. The few cytogenetic studies of MTT described in the literature have been inconclusive. Further cytogenetic analyses are needed to understand the role of chromosome X monosomy in the pathogenesis of this rare tumor. Pediatr Blood Cancer 2012; 59: 13201323. (C) 2012 Wiley Periodicals, Inc.