RESUMO
Human exposure to contaminants of emerging concern, like pesticides, has increased in the past decades. Diclofop-methyl (DFM) is a chiral herbicide that is employed as a racemic mixture (rac-DFM) in soybean and other crops against wild oats. Studies have shown that DFM has enantioselective action (higher for R-DFM), degradation (faster for S-DFM), and metabolism, producing diclofop (DF) which is also a pesticide. Although toxic effects have been reported for DFM, information regarding how DFM affects humans is lacking, especially when its chirality is concerned. In this study, the in vitro metabolism of rac-DFM and its isolated enantiomers was assessed by using a human model based on human liver microsomes. The kinetic model and parameters were obtained, and the hepatic clearance (CLH) and hepatic extraction ratio (EH) were estimated. Enzyme phenotyping was carried out by employing carboxylesterase isoforms (CES 1 and CES 2). DFM was metabolized through positive homotropic cooperativity with slight preference for (-)-DFM metabolism to (-)-DF. CLH and EH were above 19.60 mL min-1 kg-1 and 98 % for all the monitored reactions, respectively, and CES 1 was the main enzyme underlying the metabolism. These findings point out that liver contributes to DFM metabolism, which is fast, resulting in nearly complete conversion to DF after exposition to DFM.
Assuntos
Herbicidas , Praguicidas , Humanos , Herbicidas/toxicidade , Estereoisomerismo , Toxicocinética , Praguicidas/toxicidadeRESUMO
The amount of anerobic energy released during exercise might modify the initial phase of oxygen recovery (fast-O2debt) post-exercise. Therefore, the present study aimed to analyze the reliability of peak oxygen uptake ( V Ë O 2 p e a k ) estimate by back-extrapolation ( B E - V Ë O 2 p e a k ) under different swimming conditions in the severe-intensity domain, verifying how the alterations of the V Ë O 2 recovery profile and anerobic energy demand might affect B E - V Ë O 2 p e a k values. Twenty swimmers (16.7 ± 2.4 years, 173.5 ± 10.2 cm, and 66.4 ± 10.6 kg) performed an incremental intermittent step protocol (IIST: 6 × 250 plus 1 × 200 m, IIST_v200m) for the assessment of V Ë O 2 p e a k . The V Ë O 2 off-kinetics used a bi-exponential model to discriminate primary amplitude, time delay, and time constant (A1off, TD1off, and τoff) for assessment of fast-O2debt post IIST_v200m, 200-m single-trial (v200 m), and rest-to-work transition at 90% delta (v90%Δ) tests. The linear regression estimated B E - V Ë O 2 p e a k and the rate of V Ë O 2 recovery (BE-slope) post each swimming performance. The ANOVA (Sidak as post hoc) compared V Ë O 2 p e a k to the estimates of B E - V Ë O 2 p e a k in v200 m, IIST_v200 m, and v90%Δ, and the coefficient of dispersion (R2) analyzed the association between tests. The values of V Ë O 2 p e a k during IIST did not differ from B E - V Ë O 2 p e a k in v200 m, IIST_v200 m, and v90%Δ (55.7 ± 7.1 vs. 53.7 ± 8.2 vs. 56.3 ± 8.2 vs. 54.1 ± 9.1 ml kg-1 min-1, p > 0.05, respectively). However, the V Ë O 2 p e a k variance is moderately explained by B E - V Ë O 2 p e a k only in IIST_v200 m and v90%Δ (RAdj 2 = 0.44 and RAdj 2 = 0.43, p < 0.01). The TD1off and τoff responses post IIST_v200 m were considerably lower than those in both v200 m (6.1 ± 3.8 and 33.0 ± 9.5 s vs. 10.9 ± 3.5 and 47.7 ± 7.9 s; p < 0.05) and v90%Δ ( 10.1 ± 3.8 and 44.3 ± 6.3 s, p < 0.05). The BE-slope post IIST_v200m was faster than in v200 m and v90%Δ (-47.9 ± 14.6 vs. -33.0 ± 10.4 vs. -33.6 ± 13.8 ml kg-1, p < 0.01), and the total anerobic (AnaerTotal) demand was lower in IIST_v200 m (37.4 ± 9.4 ml kg-1) than in 200 m and 90%Δ (51.4 ± 9.4 and 46.2 ± 7.7 ml kg-1, p < 0.01). Finally, the τ1off was related to AnaerTotal in IIST_v200m, v200 m, and v90%Δ (r = 0.64, r = 0.61, and r = 0.64, p < 0.01). The initial phase of the V Ë O 2 recovery profile provided different (although reliable) conditions for the estimate of V Ë O 2 p e a k with BE procedures, which accounted for the moderate effect of anerobic release on V Ë O 2 off-kinetics, but compromised exceptionally the V Ë O 2 p e a k estimate in the 200-m single trial.
RESUMO
Resumen Introducción: La vegetación arbórea de selvas que se desarrolla en ambientes kársticos dominados por carbonato de calcio enfrenta la restricción de agua y nutrientes, lo que condiciona su desarrollo. Objetivo: Analizar la composición, diversidad y estructura de la vegetación arbórea que se desarrolla en afloramientos de calcio (yesales) y sus condiciones edáficas comparándolas con las presentes en vegetación secundaria (VS). Métodos: Se emplearon 17 parcelas de 1 000 m², 14 en yesales y 3 en VS. Se obtuvo una muestra compuesta de suelo por parcela y estimamos pH, conductividad eléctrica (CE-salinidad), % de carbonatos de calcio (CaCO3), materia orgánica (MO), fósforo (P) y nitrógeno (N). La diferencia en la composición de especies se evaluó mediante un análisis de similitud (ANOSIM). Empleamos métodos de rarefacción y extrapolación, estimando la diversidad mediante los números de Hill (q = 0, q = 1 y q = 2). Se utilizó un análisis de regresión linear para evaluar la influencia de las características edáficas en la diversidad, el diámetro y la altura promedios. Resultados: Los suelos en yesales presentaron concentraciones bajas de MO, P y N, valores altos de CE-salinidad y altos porcentajes de CaCO3. Se registraron 6 443 individuos de 54 especies en yesales y 594 individuos de 62 especies en la VS, siendo la composición significativamente diferente. La diversidad, los valores promedio de altura y diámetro fueron menores en yesales respecto de VS, estas diferencias estuvieron relacionadas con las condiciones edáficas. Conclusiones: La vegetación arbórea en yesales tiene una composición semejante a la de selvas subperennifolias de Calakmul. Las tallas pequeñas de los árboles están relacionadas con el alto porcentaje de CaCO3 y los altos valores de CE que condicionan la disponibilidad de MO, N y P. Este estudio apoya la idea de que precarias condiciones edáficas tienen una influencia negativa en la diversidad y la estructura horizontal y vertical de la vegetación arbórea.
Abstract Introduction: Tree vegetation of forests that develops in karst environments dominated by calcium carbonate faces the restriction of water and nutrients, which negatively affects its development. Objective: Analyze the composition, diversity, and structure of tree vegetation that develops in calcium outcrops (yesales) and their edaphic conditions compared to those present in the adjacent secondary vegetation (VS). Methods: Plots of 1 000 m² were used, 14 in yesales and 3 in VS. For soil sampling, we obtained a sample composed of each plot, and estimate pH, electrical conductivity (EC-salinity), % of calcium carbonates (CaCO3), organic matter (OM), phosphorus (P) and nitrogen content (N). The difference in species composition was estimated by similarity analysis (ANOSIM). We used rarefaction and extrapolation methods to standardize sample, and estimate diversity by Hill numbers (q = 0, q = 1 and q = 2). Linear regression was used to determine the relative influence of edaphic characteristics in diversity, average diameter, and height. Results: Soils in yesales presented low concentrations of OM, P, and N, with high values of EC-salinity and high percentages of CaCO3. In yesales, 6 443 individuals were recorded in 54 species and in the secondary vegetation 594 individuals and 62 species, the species composition being significantly different between both conditions. Diversity, average values of height, and diameter were significantly lower in yesales regarding the secondary vegetation, these differences were significantly related to edaphic conditions. Conclusions: Tree vegetation in yesales has a composition like the sub-evergreen forests of Calakmul. Small sizes in the arboreal individuals are related to the high percentage of CaCO3 and the high EC values, which partly condition the low availability of OM, N and P affecting the growth of the trees. This study supports the idea that precarious edaphic conditions have a negative influence on the diversity and horizontal and vertical structure of tree vegetation.
Assuntos
Cálcio , Estruturas Vegetais , Árvores , Sulfato de Cálcio , Aridez do Solo , MéxicoRESUMO
Kramers-Kronig (KK) equations allow us to obtain the real or imaginary part of linear, causal and time constant functions, starting from the imaginary or real part respectively. They are normally applied on different practical applications as a control method. A common problem in measurements is the lack of data in a wide-range frequency, due to some of the inherent limitations of experiments or practical limitations of the used technology. Different solutions to this problem were proved, such as several methods for extrapolation, some of which based on piecewise polynomial fit or the approach based on the expected asymptotical behavior. In this work, we propose an approach based on the symmetric extrapolation method to generate data in missing frequency ranges, to minimize the estimated error of the KK equations. The results show that with data from impedance measurements of an electrode-electrolyte interface, the adjustment error of the transformed functions can be drastically reduced to below 1%.
RESUMO
Resumen La prueba de caminata de seis minutos (PC6M) consiste en recorrer la mayor distancia posible y se caracteriza por ser una prueba de fácil realización. El objetivo de esta revisión fue examinar la relación entre las variables de distancia recorrida, patologías cardíacas, pulmonares y el consumo de oxígeno de una prueba de criterio en cinta rodante y/o cicloergómetro, y las ecuaciones de predicción del VO2 en la PC6M de Maldonado e Ingle (2006), Vanhelst (2013) y Costa (2017) para personas con patologías. El manuscrito es una revisión bibliográfica que utilizó las bases de datos Scopus y WOS, con artículos en inglés, español y portugués entre 2000 y 2017. La distancia es la variable que más se midió y que más se asoció con el VO2, encontrándose correlaciones significativas con valores de 0.01 hasta 0.8, las patologías más relacionadas con el VO2 máx. fueron la hipertensión pulmonar, enfermedad pulmonar obstructiva, insuficiencia cardíaca, disfunción sistólica ventricular y accidente cerebro-vascular y el cicloergómetro fue el más utilizado en las pruebas de criterio de VO2 máx. Solo una ecuación fue elaborada para niños que eran obesos la que incluyó distancia e IMC (Vanhelst), otra ecuación fue para adultos con enfermedad cardíaca que además incluía el sexo (Costa), una en pacientes con disfunción sistólica ventricular que aparte incorporó la edad, volumen espiratorio y hemoglobina (Ingle) y otra fórmula fue para adultos con insuficiencia cardíaca que consideró la distancia (Maldonado). Se sugiere utilizar la ecuación más apropiada y elaborar modelos predictivos para personas con diversas características.
Abstract The six-minute walk test (SMWT) consists of walking as far as possible and is characterized by being an easy test to perform. This paper examines the relationship between the variables of distance traveled, cardiac and pulmonary pathologies, and the oxygen consumption of a criterion test on treadmill and/or cycle ergometer, and the prediction equations of VO2 in the SMWT of Maldonado and Ingle (2006), Vanhelst (2013) and Costa (2017) for people with pathologies. The paper is a bibliographic review that used the Scopus and WOS databases containing articles in English, Spanish and Portuguese, published between 2000 and 2017. Distance is the variable that was most measured, and it was most associated with VO2; correlations with values from 0.01 to 0.8 were found. The pathologies most related to VO2 max were pulmonary hypertension, obstructive pulmonary disease, and ventricular heart failure and stroke; and the cycle ergometer was the most commonly used in the VO2 max criterion tests. Only one equation was created for children who were obese; it included distance and BMI (Vanhelst). Another equation was generated for adults with heart disease that also included sex (Costa). Besides, one equation was for patients with ventricular systolic dysfunction that also incorporated age, volume expiratory and hemoglobin (Ingle); another one was created for adults with heart failure, and this formula considered the distance (Maldonado). It is suggested to use the most appropriate equation and create predictive models for people with different characteristics.
Resumo O teste de caminhada de seis minutos (TC6M) consiste em andar o mais longe possível e é caracterizado como um teste fácil. O objetivo desta revisão foi examinar a relação entre as variáveis distância percorrida, patologias cardíacas, pulmonares e o consumo de oxigênio de um teste de critério em esteira e/ou ciclo ergômetro, e as equações de predição do VO 2 no TC6M de Maldonado e Ingle (2006), Vanhelst (2013) e Costa (2017) para pessoas com patologias. O manuscrito é uma revisão bibliográfica que utilizou as bases de dados Scopus e WOS, com artigos em inglês, espanhol e português entre 2000 e 2017. A distância é a variável mais medida e mais associada ao VO 2, encontrando correlações significativas com valores de 0,01 a 0,8, as patologias mais relacionadas ao VO 2 max. foram a hipertensão pulmonar, doença pulmonar obstrutiva, insuficiência cardíaca, disfunção sistólica ventricular e acidente vascular encefálico e o ciclo ergômetro foi o mais utilizado nos testes do critério VO 2 max. Apenas uma equação foi desenvolvida para crianças obesas, que incluíram distância e IMC (Vanhelst), outra equação foi para adultos com doença cardíaca que também incluiu sexo (Coast), uma em pacientes com disfunção sistólica ventricular que incorporaram a idade, volume expiratório e hemoglobina (Ingle) e outra fórmula foi para adultos com insuficiência cardíaca que considerou a distância (Maldonado). Sugere-se utilizar a equação mais adequada e desenvolver modelos preditivos para pessoas com características diversas.
Assuntos
Humanos , Masculino , Feminino , Consumo de Oxigênio , Nível de Saúde , Costa Rica , Teste de CaminhadaRESUMO
The chiral pesticide fipronil is employed as a racemic mixture to control pests. Although there are no enantioselective differences in the fipronil enantiomer activities toward target organisms, fipronil enantiomers may exhibit enantioselective differences in their bioaccumulation, toxicity, and metabolism toward non-target organisms, including humans. The present work aims to provide significant reliable enantioselective information concerning fipronil risk assessment in humans. For that, the in vitro metabolism of rac-fipronil, S-fipronil, and R-fipronil by human liver microsomes was evaluated, the in vivo enantioselective toxicokinetic parameters were predicted and the main CYP450 isoforms involved in the enantioselective metabolism were determined. The obtained results demonstrated that fipronil may undergo a clearance by the liver and it is exclusively metabolized by the CYP3A4 isoform. Although no significative stereoselective differences were observed, the results provide reliable information on fipronil risk assessment for humans.
Assuntos
Praguicidas/química , Praguicidas/metabolismo , Pirazóis/química , Pirazóis/metabolismo , Citocromo P-450 CYP3A/química , Citocromo P-450 CYP3A/metabolismo , Humanos , Microssomos Hepáticos/química , Microssomos Hepáticos/metabolismo , Praguicidas/toxicidade , Pirazóis/toxicidade , Medição de Risco , Estereoisomerismo , ToxicocinéticaRESUMO
Biosimilar products are already approved and marketed in several countries. The Food and Drug Administration has approved ten different biosimilars, and the European Medicines Agency has approved 40. Even though this scenario has provided important experience with biosimilar products, there are still challenges and unanswered questions. Up to now, a good amount of knowledge has been gathered in order to support the importance of the totality of evidence and the construction of a biosimilarity exercise for regulatory approval. In addition, the extrapolation of indications has been proved viable when a careful analysis is performed. The models for clinical trials and the use of the most sensible populations have been extensively discussed, and there is apparent homogeneity in manufacturer choices for study designs. However, some challenges remain. The lack of regulatory harmony, especially concerning naming, the marketed intended copies, the interchangeability, and the biosimilars in orphan diseases are some of those and are the focus of discussion in this review.
RESUMO
The biotechnology-derived medicines known as biosimilars are defined as non-originator treatments that have demonstrated quality, efficacy, and safety comparable to the reference biologic drug. Clinical trials have shown that the infliximab biosimilar, CT-P13, and the candidates for the adalimumab biosimilars, ABP 501 and ZRC 3197, are not significantly different, with respect to efficacy and safety, from the originator drugs in patients with other autoimmune diseases. However, controversy has arisen over the use of biosimilars in inflammatory bowel disease, due to the incipient evidence not only in patients with no previous biotechnology treatment, but also in patients in remission, that could be switched to a biosimilar for non-medical reasons. The present review is the first critical analysis by different specialists in the area of gastroenterology on the use of biosimilars in inflammatory bowel disease, the evidence on interchangeability, the extrapolation of indications, efficacy, safety, immunogenicity, and the clinical impact of the Mexican health regulations. The aim of our review was to make the positioning and recommendations of these new therapeutic options known, given that they have a potential cost-benefit for both patients and healthcare institutions.
Assuntos
Medicamentos Biossimilares/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Adalimumab , Humanos , Infliximab , Legislação de Medicamentos , MéxicoRESUMO
OBJECTIVE: The risks and benefits of the participation of kidney transplant recipients in randomized clinical trials (RCTs) investigating new immunosuppressive therapies are unknown. DESIGN AND SETTING: We included patients from 12 prospective phase II/III RCTs randomized to the experimental (G1, n=319) or standard-of-care internal control group (G2, n=118). We constructed two additional external control groups with (G3, n=319) or without (G4, n=319) matching inclusion/exclusion criteria based on transplant date. The primary outcome analysis was the composite clinical efficacy failure, defined as biopsy-proven acute rejection (BPAR), graft loss, death, or loss to follow-up 12 months after kidney transplantation. RESULTS: Survival free of composite clinical efficacy failure was higher among participants in RCT, without difference between experimental or standard-of-care therapy (80â3 vs 78â0 vs 69â9 vs 66â1%, P<.001), respectively. Patient (98.1 vs 99.2 vs 96.9 vs 91.8 P<.001) and graft (94.0 vs 98.3 vs 90.9 vs 82.4) survivals were also higher in G1 compared to G4, but no differences in survival free of BPAR were observed (85.3 vs 78.8 vs 82.8 vs 81.2 P>.05), respectively. CONCLUSION: These findings suggested that new treatments investigated in kidney transplant recipients are not associated with detectable harm compared to standard of care.
Assuntos
Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Adolescente , Adulto , Idoso , Interpretação Estatística de Dados , Feminino , Seguimentos , Rejeição de Enxerto/mortalidade , Humanos , Modelos Logísticos , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Resumen La enfermedad inflamatoria intestinal (EII) es un término con el que se conocen varias entidades, las 2 más importantes son: la colitis ulcerativa idiopática (CUI) y la enfermedad de Crohn (EC), cuyo origen es multifactorial y se caracterizan por un fenómeno inflamatorio, crónico, recurrente con diferentes grados de severidad del tubo digestivo; pero además con afectación potencial de otros órganos. En la última década ha habido un renovado interés en dichas entidades, debido a una incidencia creciente de estas, pero también debido al desarrollo de medicamentos que por primera vez están cambiando la historia natural de estas enfermedades: son los medicamentos llamados biológicos, que son aquellos producidos o derivados de organismos vivos y representan el sector de mayor crecimiento en la industria farmacéutica mundial. Debido al interés comercial, se han desarrollado y sometido a las autoridades reguladoras productos no originadores; similares, pero no idénticos a los productos de referencia. La Agencia Europea de Medicamentos (EMA) aprobó el primer biosimilar del infliximab para todas las indicaciones en las cuales este estaba aprobado, incluidas: colitis ulcerativa moderada a severa en todas las edades, EC moderada a severa en todas las edades, al igual que EC fistulizante, artritis psoriásica (AP), psoriasis, espondilitis anquilosante (EA) y artritis reumatoide (AR) (1). En esta revisión nos proponemos definir lo que son estos productos al igual que algunos conceptos relacionados (extrapolación, sustitución e intercambiabilidad), además hacer una revisión histórica de su desarrollo, sus indicaciones actuales, las posiciones de las diferentes asociaciones científicas al respecto y, lo más importante, brindar datos de la vida real en cuanto a su efectividad, seguridad y costos en los diferentes países donde se han estado usando.
Abstract The term Inflammatory Bowel Disease (IBD) is used to identify several entities, the two most important of which are Idiopathic Ulcerative Colitis (IUC) and Crohn's Disease (EC). Both are multifactorial in origin, are chronic and recurrent, are characterized by inflammation, have varying degrees of severity, and potentially involve other organs. In the last decade there has been renewed interest in these entities due to growing incidence and to the development of drugs called biologicals. For the first time, these drugs have changed the natural history of these diseases. They are produced or derived from living organisms and represent the fastest growing sector in the global pharmaceutical industry. Due to commercial interest, products similar but not identical to the original products have been developed and submitted to regulatory authorities. The European Medicines Agency has approved the first biosimilar for infliximab for all indications for which it has been approved. These include moderate to severe ulcerative colitis (UC) at all ages, moderate to severe Crohn's disease (CD) at all ages, fistulizing Crohn's disease, Psoriasic arthritis, Psoriasis, Ankylosing Spondylitis, and Rheumatoid Arthritis. 1 In this review, we define what these products are, as well as some concepts coined for their usage including extrapolation, substitution and interchangeability. We also make a historical review of their development, current indications, the positions of various scientific associations with respect to them, and - most importantly - provide real-life data regarding their effectiveness, safety and costs in countries where they have been used.
Assuntos
Fatores Biológicos , Medicamentos Biossimilares , Intercambialidade de MedicamentosRESUMO
Beta Secondary Standard 2 (BSS 2) provides beta radiation fields with certified values of absorbed dose to tissue and the derived operational radiation protection quantities. As part of the quality assurance, the reliability of the CDTN BSS2 system was verified through measurements in the 90Sr/90Y and 85Kr beta radiation fields. Absorbed dose rates and their angular variation were measured with a 23392 model PTW extrapolation chamber and with Gafchromic radiochromic films on a PMMA slab phantom. The feasibility of using both methods was analyzed.
RESUMO
Digital soil mapping is an alternative for the recognition of soil classes in areas where pedological surveys are not available. The main aim of this study was to obtain a digital soil map using artificial neural networks (ANN) and environmental variables that express soil-landscape relationships. This study was carried out in an area of 11,072 ha located in the Barra Bonita municipality, state of São Paulo, Brazil. A soil survey was obtained from a reference area of approximately 500 ha located in the center of the area studied. With the mapping units identified together with the environmental variables elevation, slope, slope plan, slope profile, convergence index, geology and geomorphic surfaces, a supervised classification by ANN was implemented. The neural network simulator used was the Java NNS with the learning algorithm "back propagation." Reference points were collected for evaluating the performance of the digital map produced. The occurrence of soils in the landscape obtained in the reference area was observed in the following digital classification: medium-textured soils at the highest positions of the landscape, originating from sandstone, and clayey loam soils in the end thirds of the hillsides due to the greater presence of basalt. The variables elevation and slope were the most important factors for discriminating soil class through the ANN. An accuracy level of 82% between the reference points and the digital classification was observed. The methodology proposed allowed for a preliminary soil classification of an area not previously mapped using mapping units obtained in a reference area.(AU)
Assuntos
Mudança Climática , Fazendeiros , Percepção , Enquete Socioeconômica , Adaptação a Desastres , Agricultura , Processos Climáticos , Fatores Socioeconômicos , Análise de RegressãoRESUMO
Digital soil mapping is an alternative for the recognition of soil classes in areas where pedological surveys are not available. The main aim of this study was to obtain a digital soil map using artificial neural networks (ANN) and environmental variables that express soil-landscape relationships. This study was carried out in an area of 11,072 ha located in the Barra Bonita municipality, state of São Paulo, Brazil. A soil survey was obtained from a reference area of approximately 500 ha located in the center of the area studied. With the mapping units identified together with the environmental variables elevation, slope, slope plan, slope profile, convergence index, geology and geomorphic surfaces, a supervised classification by ANN was implemented. The neural network simulator used was the Java NNS with the learning algorithm "back propagation." Reference points were collected for evaluating the performance of the digital map produced. The occurrence of soils in the landscape obtained in the reference area was observed in the following digital classification: medium-textured soils at the highest positions of the landscape, originating from sandstone, and clayey loam soils in the end thirds of the hillsides due to the greater presence of basalt. The variables elevation and slope were the most important factors for discriminating soil class through the ANN. An accuracy level of 82% between the reference points and the digital classification was observed. The methodology proposed allowed for a preliminary soil classification of an area not previously mapped using mapping units obtained in a reference area.
Assuntos
Adaptação a Desastres , Enquete Socioeconômica , Fazendeiros , Mudança Climática , Percepção , Agricultura , Análise de Regressão , Fatores Socioeconômicos , Processos ClimáticosRESUMO
RATIONALE, AIMS AND OBJECTIVES: Increased awareness of the gap between controlled research and medical practice has raised concerns over whether the special attention of doctors to probability estimates from clinical trials really improves the care of individuals. Evidence-based medicine has acknowledged that research results are not applicable to all kinds of patients, and consequently, has attempted to overcome this limitation by introducing improvements in the design and analysis of clinical trials. METHODS: A clinical case is used to highlight the premises required to support reasonable extrapolations from controlled research to individuals. Then, the prospects of two key methodological improvements - pragmatic randomized controlled trials and subgroup analysis - are critically appraised. RESULTS: A principle to guide therapeutic inferences is suggested. According to this principle, the probabilities of interest for purposes of therapeutic decision making are those of the set defined by everything that is relevant to the patient and the outcome of interest at the time of the decision. It is argued that the conditions necessary to authorize automatic extrapolations of research results to specific patients are highly demanding. Furthermore, these requirements are rarely accomplished in real practice, even in the event that probability estimates come from samples generally taken as representative and are derived from specific subsets of patients. CONCLUSIONS: Clinicians should generally avoid unreflective extrapolations from research and address, as explicitly as possible, the challenge of estimating probabilities for individual patients. A key element of this task is the integration of data from research and non-research sources.
Assuntos
Medicina Baseada em Evidências , Humanos , Probabilidade , Resultado do TratamentoRESUMO
Health economic evaluations require estimates of expected survival from patients receiving different interventions, often over a lifetime. However, data on the patients of interest are typically only available for a much shorter follow-up time, from randomised trials or cohorts. Previous work showed how to use general population mortality to improve extrapolations of the short-term data, assuming a constant additive or multiplicative effect on the hazards for all-cause mortality for study patients relative to the general population. A more plausible assumption may be a constant effect on the hazard for the specific cause of death targeted by the treatments. To address this problem, we use independent parametric survival models for cause-specific mortality among the general population. Because causes of death are unobserved for the patients of interest, a polyhazard model is used to express their all-cause mortality as a sum of latent cause-specific hazards. Assuming proportional cause-specific hazards between the general and study populations then allows us to extrapolate mortality of the patients of interest to the long term. A Bayesian framework is used to jointly model all sources of data. By simulation, we show that ignoring cause-specific hazards leads to biased estimates of mean survival when the proportion of deaths due to the cause of interest changes through time. The methods are applied to an evaluation of implantable cardioverter defibrillators for the prevention of sudden cardiac death among patients with cardiac arrhythmia. After accounting for cause-specific mortality, substantial differences are seen in estimates of life years gained from implantable cardioverter defibrillators.
Assuntos
Bioestatística/métodos , Análise de Sobrevida , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/prevenção & controle , Arritmias Cardíacas/terapia , Teorema de Bayes , Estudos de Coortes , Simulação por Computador , Análise Custo-Benefício , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis/economia , Humanos , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Prevenção Secundária/economia , Prevenção Secundária/estatística & dados numéricosRESUMO
(90)Sr+(90)Y clinical applicators are used for brachytherapy in Brazilian clinics even though they are not manufactured anymore. Such sources must be calibrated periodically, and one of the calibration methods in use is ionometry with extrapolation ionization chambers. (90)Sr+(90)Y clinical applicators were calibrated using an extrapolation minichamber developed at the Calibration Laboratory at IPEN. The obtained results agree satisfactorily with the data provided in calibration certificates of the sources.
Assuntos
Braquiterapia/instrumentação , Braquiterapia/normas , Radiometria/instrumentação , Radiometria/normas , Radioisótopos de Estrôncio/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Partículas beta/uso terapêutico , Brasil , Calibragem/normas , Oftalmopatias/radioterapia , Humanos , Dosagem Radioterapêutica , Dermatopatias/radioterapia , Radioisótopos de Estrôncio/normas , Radioisótopos de Estrôncio/uso terapêutico , Radioisótopos de Ítrio/normas , Radioisótopos de Ítrio/uso terapêuticoRESUMO
Abstract. A 96 h acute silver toxicity test was performed in order to determine silver toxicity (LC50) to a local fish species (Cnesterodon decemmaculatus) in a river with extreme water-quality characteristics (Pilcomayo River, South America) and evaluate a cross-fish-species extrapolation of the Biotic Ligand Model. The dissolved silver concentrations tested were 0.095, 0.148, 0.175 and 0.285 mg Ag L−1. The 96 h Ag LC50 calculated for C. decemmaculatus was 0.14 mg L−1 (0.18 - 0.10) and the value predicted by BLM for Pimephales promelas was 0.051 mg Ag L−1. Test water elevated hardness may have exerted some protective effect. High mean water pH may have exerted a major protective effect by reducing silver free ion form and causing silver precipitation. The mortality pattern observed in this toxicity test may lend some support to a relationship between gill silver accumulation and mortality. A cross-fish-species extrapolation of Ag BLM for P. promelas was not valid in Pilcomayo River water and experimental conditions of this toxicity test.(AU)
Con el objeto de determinar la toxicidad de la plata en un pez nativo (Cnesterodon decemmaculatus), se llevó a cabo un ensayo estático de toxicidad aguda a 96 horas en un agua natural con características de calidad de agua, extremas (río Pilcomayo, Sudamérica). Asimismo, se evaluó una posible extrapolación inter-especie del Modelo del Ligando Biótico en el agua experimental. La concentración inicial de plata en solución en los distintos tratamientos fue de 0,095; 0,148; 0,175 y 0,285 mg Ag L −1 . La CL50 a las 96 horas calculada para C. decemmaculatus fue de 0,14 (0.18 - 0.10) mg Ag L−1 y el valor predicho por el BLM para Pimephales promelas fue de 0,051 mg Ag L−1. La elevada dureza del agua experimental pudo haber tenido algún efecto protector frente a la toxicidad de la plata. El valor medio de pH del ensayo fue elevado y posiblemente tuvo un gran efecto protector por reducción de la forma iónica libre y precipitación del metal. El patrón de mortalidad observado en este ensayo de toxicidad apoyaría la relación causa-efecto entre acumulación de plata en las branquias y mortalidad. La extrapolación inter-especie del BLM para P. promelas no resultó válida en el agua del río Pilcomayo y en las condiciones experimentales de este ensayo.(AU)
RESUMO
Abstract. A 96 h acute silver toxicity test was performed in order to determine silver toxicity (LC50) to a local fish species (Cnesterodon decemmaculatus) in a river with extreme water-quality characteristics (Pilcomayo River, South America) and evaluate a cross-fish-species extrapolation of the Biotic Ligand Model. The dissolved silver concentrations tested were 0.095, 0.148, 0.175 and 0.285 mg Ag L−1. The 96 h Ag LC50 calculated for C. decemmaculatus was 0.14 mg L−1 (0.18 - 0.10) and the value predicted by BLM for Pimephales promelas was 0.051 mg Ag L−1. Test water elevated hardness may have exerted some protective effect. High mean water pH may have exerted a major protective effect by reducing silver free ion form and causing silver precipitation. The mortality pattern observed in this toxicity test may lend some support to a relationship between gill silver accumulation and mortality. A cross-fish-species extrapolation of Ag BLM for P. promelas was not valid in Pilcomayo River water and experimental conditions of this toxicity test.
Con el objeto de determinar la toxicidad de la plata en un pez nativo (Cnesterodon decemmaculatus), se llevó a cabo un ensayo estático de toxicidad aguda a 96 horas en un agua natural con características de calidad de agua, extremas (río Pilcomayo, Sudamérica). Asimismo, se evaluó una posible extrapolación inter-especie del Modelo del Ligando Biótico en el agua experimental. La concentración inicial de plata en solución en los distintos tratamientos fue de 0,095; 0,148; 0,175 y 0,285 mg Ag L −1 . La CL50 a las 96 horas calculada para C. decemmaculatus fue de 0,14 (0.18 - 0.10) mg Ag L−1 y el valor predicho por el BLM para Pimephales promelas fue de 0,051 mg Ag L−1. La elevada dureza del agua experimental pudo haber tenido algún efecto protector frente a la toxicidad de la plata. El valor medio de pH del ensayo fue elevado y posiblemente tuvo un gran efecto protector por reducción de la forma iónica libre y precipitación del metal. El patrón de mortalidad observado en este ensayo de toxicidad apoyaría la relación causa-efecto entre acumulación de plata en las branquias y mortalidad. La extrapolación inter-especie del BLM para P. promelas no resultó válida en el agua del río Pilcomayo y en las condiciones experimentales de este ensayo.
Assuntos
Animais , Poecilia , Nitrato de Prata/toxicidade , Prata/toxicidade , Testes de Toxicidade Aguda/métodos , Argentina , Poluição de Rios/análiseRESUMO
O objetivo deste estudo foi avaliar o protocolo de contenção química com cetamina S(+) e midazolam em bugios-ruivos, comparando o cálculo de doses pelo método convencional e o método de extrapolação alométrica. Foram utilizados 12 macacos bugios (Alouatta guariba clamitans) hígidos, com peso médio de 4,84±0,97kg, de ambos os sexos. Após jejum alimentar de 12 horas e hídrico de seis horas, realizou-se contenção física manual e aferiram-se os seguintes parâmetros: frequência cardíaca (FC), frequência respiratória (f), tempo de preenchimento capilar (TPC), temperatura retal (TR), pressão arterial sistólica não invasiva (PANI) e valores de hemogasometria arterial. Posteriormente, os animais foram alocados em dois grupos: GC (Grupo Convencional, n=06), os quais receberam cetamina S(+) (5mg kg-1) e midazolam (0,5mg kg-1), pela via intramuscular, com doses calculadas pelo método convencional; e GA (Grupo Alometria, n=06), os quais receberam o mesmo protocolo, pela mesma via, utilizando-se as doses calculadas pelo método de extrapolação alométrica. Os parâmetros descritos foram mensurados novamente nos seguintes momentos: M5, M10, M20 e M30 (cinco, 10, 20 e 30 minutos após a administração dos fármacos, respectivamente). Também foram avaliados: qualidade de miorrelaxamento, reflexo podal e caudal, pinçamento interdigital, tempo para indução de decúbito, tempo hábil de sedação, qualidade de sedação, e tempo e qualidade de recuperação. O GA apresentou menor tempo para indução ao decúbito, maior grau e tempo de sedação, bem como redução significativa da FC e PANI de M5 até M30, quando comparado ao GC. Conclui-se que o grupo no qual o cálculo de dose foi realizado por meio da alometria (GA) apresentou melhor grau de relaxamento muscular e sedação, sem produzir depressão cardiorrespiratória significativa.
The aim of this study was to evaluate a protocol of chemical restraint comparing the conventional method of calculation (weight dose) and allometric extrapolation. Twelve healthy red howler monkeys (Alouatta guariba clamitans), average weight 4.84±0.97kg, male and female, were used for this study. After a 12-hour period of food restriction and 6 hours of water restriction, the animals were physically restraint and the following parameters were measured: heart rate (HR), respiratory rate (RR), capillary refill time (CRT), rectal temperature (RT), non invasive systolic arterial pressure (NISAP) and arterial blood gases analysis. The animals were distributed into two groups: CG (Conventional Group, n=6), in which the animals received S(+) ketamine (5mg kg-1) and midazolam (0.5mg kg-1), by intramuscular (IM) injection; and AG (Allometry Group, n=6), in which the animals also received S(+) ketamine and midazolan IM, but the doses were calculated by allometric extrapolation. Parameters were evaluated at the following moments: M5, M10, M20 and M30 (5, 10, 20 and 30 minutes after IM injection, respectively). Muscle relaxation, pedal and caudal reflexes, interdigital pinch, recumbency time, sedation's quality and duration, and recovery time and its quality were also evaluated. The AG had a faster time for recumbency, higher period and quality of sedation, and a significantly reduction on HR and SAP from M5 to M30 when compared to CG. It was concluded that allometric extrapolation presented a better muscle relaxation and sedation without significant cardiorespiratory depression.
RESUMO
The aim of this study was to evaluate a protocol of chemical restraint comparing the conventional method of calculation (weight dose) and allometric extrapolation. Twelve healthy red howler monkeys (Alouatta guariba clamitans), average weight 4.84±0.97kg, male and female, were used for this study. After a 12-hour period of food restriction and 6 hours of water restriction, the animals were physically restraint and the following parameters were measured: heart rate (HR), respiratory rate (RR), capillary refill time (CRT), rectal temperature (RT), non invasive systolic arterial pressure (NISAP) and arterial blood gases analysis. The animals were distributed into two groups: CG (Conventional Group, n=6), in which the animals received S(+) ketamine (5mg kg-1) and midazolam (0.5mg kg-1), by intramuscular (IM) injection; and AG (Allometry Group, n=6), in which the animals also received S(+) ketamine and midazolan IM, but the doses were calculated by allometric extrapolation. Parameters were evaluated at the following moments: M5, M10, M20 and M30 (5, 10, 20 and 30 minutes after IM injection, respectively). Muscle relaxation, pedal and caudal reflexes, interdigital pinch, recumbency time, sedation's quality and duration, and recovery time and its quality were also evaluated. The AG had a faster time for recumbency, higher period and quality of sedation, and a significantly reduction on HR and SAP from M5 to M30 when compared to CG. It was concluded that allometric extrapolation presented a better muscle relaxation and sedation without significant cardiorespiratory depression.
O objetivo deste estudo foi avaliar o protocolo de contenção química com cetamina S(+) e midazolam em bugios-ruivos, comparando o cálculo de doses pelo método convencional e o método de extrapolação alométrica. Foram utilizados 12 macacos bugios (Alouatta guariba clamitans) hígidos, com peso médio de 4,84±0,97kg, de ambos os sexos. Após jejum alimentar de 12 horas e hídrico de seis horas, realizou-se contenção física manual e aferiram-se os seguintes parâmetros: frequência cardíaca (FC), frequência respiratória (f), tempo de preenchimento capilar (TPC), temperatura retal (TR), pressão arterial sistólica não invasiva (PANI) e valores de hemogasometria arterial. Posteriormente, os animais foram alocados em dois grupos: GC (Grupo Convencional, n=06), os quais receberam cetamina S(+) (5mg kg-1) e midazolam (0,5mg kg-1), pela via intramuscular, com doses calculadas pelo método convencional; e GA (Grupo Alometria, n=06), os quais receberam o mesmo protocolo, pela mesma via, utilizando-se as doses calculadas pelo método de extrapolação alométrica. Os parâmetros descritos foram mensurados novamente nos seguintes momentos: M5, M10, M20 e M30 (cinco, 10, 20 e 30 minutos após a administração dos fármacos, respectivamente). Também foram avaliados: qualidade de miorrelaxamento, reflexo podal e caudal, pinçamento interdigital, tempo para indução de decúbito, tempo hábil de sedação, qualidade de sedação, e tempo e qualidade de recuperação. O GA apresentou menor tempo para indução ao decúbito, maior grau e tempo de sedação, bem como redução significativa da FC e PANI de M5 até M30, quando comparado ao GC. Conclui-se que o grupo no qual o cálculo de dose foi realizado por meio da alometria (GA) apresentou melhor grau de relaxamento muscular e sedação, sem produzir depressão cardiorrespiratória significativa.