Methods for Equivalence and Noninferiority Testing

Classical hypothesis testing focuses on testing whether treatments have differential effects on outcome. However, sometimes clinicians may be more interested in determining whether treatments are equivalent or whether one has noninferior outcomes. We review the hypotheses for these noninferiority and equivalence research questions, consider power and sample size issues, and discuss how to perform such a test for both binary and survival outcomes. The methods are illustrated on 2 recent studies in hematopoietic cell transplantation.

Enhanced classification of Chagas serologic results and epidemiologic characteristics of seropositive donors at three large blood centers in Brazil

BACKGROUND: A major problem in Chagas disease donor screening is the high frequency of samples with inconclusive results. The objective of this study was to describe patterns of serologic results among donors to the three Brazilian REDS-II blood centers and correlate with epidemiologic characteristics. STUDY DESIGN AND METHODS: The centers screened donor samples with one Trypanosoma cruzi lysate enzyme immunoassay (EIA). EIA-reactive samples were tested with a second lysate EIA, a recombinant-antigen based EIA, and an immunfluorescence assay. Based on the serologic results, samples were classified as confirmed positive (CP), probable positive (PP), possible other parasitic infection (POPI), and false positive (FP). RESULTS: In 2007 to 2008, a total of 877 of 615,433 donations were discarded due to Chagas assay reactivity. The prevalences (95% confidence intervals [CIs]) among first-time donors for CP, PP, POPI, and FP patterns were 114 (99-129), 26 (19-34), 10 (5-14), and 96 (82-110) per 100,000 donations, respectively. CP and PP had similar patterns of prevalence when analyzed by age, sex, education, and location, suggesting that PP cases represent true T. cruzi infections; in contrast the demographics of donors with POPI were distinct and likely unrelated to Chagas disease. No CP cases were detected among 218,514 repeat donors followed for a total of 718,187 person-years. CONCLUSION: We have proposed a classification algorithm that may have practical importance for donor counseling and epidemiologic analyses of T. cruzi-seroreactive donors. The absence of incident T. cruzi infections is reassuring with respect to risk of window phase infections within Brazil and travel-related infections in nonendemic countries such as the United States.

Determination of the susceptibility of Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) to ivermectin and fipronil by Larval Immersion Test (LIT) in Uruguay

Rhipicephalus (Boophilus) microplus is an important cattle pest in Uruguay, and the law regulates its control. It is resistant to organophosphates, synthetic pyrethroids and, as recently discovered, to fipronil. Resistance to macrocyclic lactones (MLs) and amitraz have not been documented; however, veterinarians and farmers have reported treatment failures. The objective of the present work was to study the susceptibility of cattle tick strains from different Uruguayan counties to ivermectin (IVM) and fipronil by using the Larval Immersion Test (LIT). The Mozo strain was used as the susceptible reference strain. From 2007 to 2009, twenty-eight tick populations were collected from different cattle farms with and without history of IVM or fipronil use. A probit analysis estimated dose-mortality regressions, lethal concentrations (LC), and confidence intervals. The resistance ratio (RR) was determined at the LC(50) and LC(90) estimates. To classify a tick population in relation to resistance, three categories based on a statistical analysis of LC and RR between field populations and Mozo strains were defined: susceptible (no differences), incipient resistance (differences and RR(50) < 2) and resistant (differences and RR(50) >= 2). Eighteen field populations were tested with IVM and five of them presented a RR(50) range between 1.35 and 1.98 and the LC(50/90), which is statistically different from the Mozo strain (incipient resistance). However, the RR(90) increases >= 2 in four of the populations, confirming that tick resistance to IVM is emergent. The low RR values obtained could be a result of a low frequency of treatments with IVM. Twenty-seven tick populations were tested with fipronil and six were diagnosed as resistant according to the LIT. Cross-resistance was not observed between fipronil and IVM on these tick populations. The current study presents different R. (B.) microplus populations with an incipient resistance to IVM, and indicates that the fipronil tick resistance is restricted to certain areas in Uruguay. (c) 2011 Elsevier B.V. All rights reserved.

Influence of hardwood, softwoodand fractionated pulp in a stratifiedthree-layered fine paper : Lövved, barrved och fraktionerad massa ochdess inverkan på ett treskiktat finpapper

Four different trials of stratified three-layered fine paper, of sulphate pulp, were performed to investigate if stratified fine fraction or fibres from birch can improve the properties of a paper compared to a reference sheet. All trials had five different scenarios and each scenario was calendered with different linear load. All sheets had a grammage of 80 g/m2.In the first trial, the paper contained birch, pine and filler of calciumcarbonate (marble), and was manufactured with the pilot paper machine XPM and the stratified headbox Formator at RCF (Stora Enso Research Center in Falun). The furnish consisted of 75% birch and 25% pine.The second trial contained coated sheets with paper from trial one as the base paper. The coating slip contained calciumcarbonate and clay and the amount was approximately 10-12 g/m2.The third trial, also with birch and pine but without filler, was performed at STFI (Skogsindustrins Tekniska Forskningsinstitut in Stockholm) with the laboratory scaled paper machine StratEx and the stratified headbox AQ-vanes. The furnish consisted of 75% birch and 25% pine, except for one scenario which contained of 75% pine and 25% birch.The last trial contained fractionated pulp of birch and pine and was performed at STFI. 50% was fine fraction and 50% was coarse fraction.This test does not show any clear benefits of making stratified sheets of birch and pine when it comes to properties such as bending stiffness, tensile index and surface smoothness. The retention can be improved with birch in the surface plies. It is possible that the formation can be improved with birch in the surface plies and pine in the middle ply. It is also possible that fine fraction in the surface plies and coarse fraction in the middle ply can improve both surface smoothness and bending stiffness. The results in this test are shown with confidence intervals which points out the difficulties of analysing sheets manufactured with a pilot paper machine or a laboratory scaled paper machine.

The importance of body-mass exponent optimization for evaluation of performance capability in cross-country skiing

Introduction Performance in cross-country skiing is influenced by the skier’s ability to continuously produce propelling forces and force magnitude in relation to the net external forces. A surrogate indicator of the “power supply” in cross-country skiing would be a physiological variable that reflects an important performance-related capability, whereas the body mass itself is an indicator of the “power demand” experienced by the skier. To adequately evaluate an elite skier’s performance capability, it is essential to establish the optimal ratio between the physiological variable and body mass. The overall aim of this doctoral thesis was to investigate the importance of body-mass exponent optimization for the evaluation of performance capability in cross-country skiing. Methods In total, 83 elite cross-country skiers (56 men and 27 women) volunteered to participate in the four studies. The physiological variables of maximal oxygen uptake (V̇O2max) and oxygen uptake corresponding to a blood-lactate concentration of 4 mmol∙l-1 (V̇O2obla) were determined while treadmill roller skiing using the diagonal-stride technique; mean oxygen uptake (V̇O2dp) and upper-body power output (Ẇ) were determined during double-poling tests using a ski-ergometer. Competitive performance data for elite male skiers were collected from two 15-km classical-technique skiing competitions and a 1.25-km sprint prologue; additionally, a 2-km double-poling roller-skiing time trial using the double-poling technique was used as an indicator of upper-body performance capability among elite male and female junior skiers. Power-function modelling was used to explain the race and time-trial speeds based on the physiological variables and body mass. Results The optimal V̇O2max-to-mass ratios to explain 15-km race speed were V̇O2max divided by body mass raised to the 0.48 and 0.53 power, and these models explained 68% and 69% of the variance in mean skiing speed, respectively; moreover, the 95% confidence intervals (CI) for the body-mass exponents did not include either 0 or 1. For the modelling of race speed in the sprint prologue, body mass failed to contribute to the models based on V̇O2max, V̇O2obla, and V̇O2dp. The upper-body power output-to-body mass ratio that optimally explained time-trial speed was Ẇ ∙ m-0.57 and the model explained 63% of the variance in speed. Conclusions The results in this thesis suggest that V̇O2max divided by the square root of body mass should be used as an indicator of performance in 15-km classical-technique races among elite male skiers rather than the absolute or simple ratio-standard scaled expression. To optimally explain an elite male skier’s performance capability in sprint prologues, power-function models based on oxygen-uptake variables expressed absolutely are recommended. Moreover, to evaluate elite junior skiers’ performance capabilities in 2-km double-poling roller-skiing time trials, it is recommended that Ẇ divided by the square root of body mass should be used rather than absolute or simple ratio-standard scaled expression of power output.

A Gradient-Type Method For Real-Time State Estimation Of Water Distribution Networks

Drinking water distribution networks risk exposure to malicious or accidental contamination. Several levels of responses are conceivable. One of them consists to install a sensor network to monitor the system on real time. Once a contamination has been detected, this is also important to take appropriate counter-measures. In the SMaRT-OnlineWDN project, this relies on modeling to predict both hydraulics and water quality. An online model use makes identification of the contaminant source and simulation of the contaminated area possible. The objective of this paper is to present SMaRT-OnlineWDN experience and research results for hydraulic state estimation with sampling frequency of few minutes. A least squares problem with bound constraints is formulated to adjust demand class coefficient to best fit the observed values at a given time. The criterion is a Huber function to limit the influence of outliers. A Tikhonov regularization is introduced for consideration of prior information on the parameter vector. Then the Levenberg-Marquardt algorithm is applied that use derivative information for limiting the number of iterations. Confidence intervals for the state prediction are also given. The results are presented and discussed on real networks in France and Germany.

Previsão em tempo atual de cheias com uso de sistema especialista difuso

Sistemas de previsão de cheias podem ser adequadamente utilizados quando o alcance é suficiente, em comparação com o tempo necessário para ações preventivas ou corretivas. Além disso, são fundamentalmente importantes a confiabilidade e a precisão das previsões. Previsões de níveis de inundação são sempre aproximações, e intervalos de confiança não são sempre aplicáveis, especialmente com graus de incerteza altos, o que produz intervalos de confiança muito grandes. Estes intervalos são problemáticos, em presença de níveis fluviais muito altos ou muito baixos. Neste estudo, previsões de níveis de cheia são efetuadas, tanto na forma numérica tradicional quanto na forma de categorias, para as quais utiliza-se um sistema especialista baseado em regras e inferências difusas. Metodologias e procedimentos computacionais para aprendizado, simulação e consulta são idealizados, e então desenvolvidos sob forma de um aplicativo (SELF – Sistema Especialista com uso de Lógica “Fuzzy”), com objetivo de pesquisa e operação. As comparações, com base nos aspectos de utilização para a previsão, de sistemas especialistas difusos e modelos empíricos lineares, revelam forte analogia, apesar das diferenças teóricas fundamentais existentes. As metodologias são aplicadas para previsão na bacia do rio Camaquã (15543 km2), para alcances entre 10 e 48 horas. Dificuldades práticas à aplicação são identificadas, resultando em soluções as quais constituem-se em avanços do conhecimento e da técnica. Previsões, tanto na forma numérica quanto categorizada são executadas com sucesso, com uso dos novos recursos. As avaliações e comparações das previsões são feitas utilizandose um novo grupo de estatísticas, derivadas das freqüências simultâneas de ocorrência de valores observados e preditos na mesma categoria, durante a simulação. Os efeitos da variação da densidade da rede são analisados, verificando-se que sistemas de previsão pluvio-hidrométrica em tempo atual são possíveis, mesmo com pequeno número de postos de aquisição de dados de chuva, para previsões sob forma de categorias difusas.

Diabetes mellitus : magnitude das hospitalizações na rede pública do Brasil, 1999-2001

Contexto: O diabetes mellitus (DM) é uma causa importante de morbimortalidade nas sociedades ocidentais devido à carga de sofrimento, incapacidade, perda de produtividade e morte prematura que provoca. No Brasil, seu impacto econômico é desconhecido. Objetivos: Dimensionar a participação do DM nas hospitalizações da rede pública brasileira (1999-2001), colaborando na avaliação dos custos diretos. Especificamente, analisar as hospitalizações (327.800) e os óbitos hospitalares (17.760) por DM como diagnóstico principal (CID-10 E10-E14 e procedimento realizado) e estimar as hospitalizações atribuíveis ao DM, incluindo as anteriores e aquelas por complicações crônicas (CC) e condições médicas gerais (CMG). Métodos: A partir de dados do Sistema de Informação Hospitalar do Sistema Único de Saúde (SIH/SUS) (37 milhões de hospitalizações), foram calculados indicadores por região de residência do paciente e sexo (ajustados por idade pelo método direto, com intervalos de confiança de 95%), faixas etárias, médias de permanência e de gastos por internação e populacional em US$. Realizou-se regressão logística múltipla para o desfecho óbito. As prevalências de DM foram combinadas aos riscos relativos de hospitalização por CC e CMG (metodologia do risco atribuível) e somadas às internações por DM como diagnóstico principal. Utilizou-se análise de sensibilidade para diferentes prevalências e riscos relativos. Resultados: Os coeficientes de hospitalizações e de óbitos hospitalares e a letalidade por DM como diagnóstico principal atingiram respectivamente 6,4/104hab., 34,9/106hab. e 5,4%. As mulheres apresentaram os coeficientes mais elevados, porém os homens predominaram na letalidade em todas as regiões. O gasto médio (US$ 150,59) diferiu significativamente entre as internações com e sem óbito, mas a média de permanência (6,4 dias) foi semelhante. O gasto populacional equivaleu a US$ 969,09/104hab. As razões de chances de óbito foram maiores para homens, pacientes ≥75 anos, e habitantes das regiões Nordeste e Sudeste. As hospitalizações atribuíveis ao DM foram estimadas em 836,3 mil/ano (49,3/104hab.), atingindo US$ 243,9 milhões/ano (US$ 14,4 mil/104hab.). DM como diagnóstico principal (13,1%), CC (41,5%) e CMG (45,4%) responderam por 6,7%, 51,4% e 41,9% respectivamente dos gastos. O valor médio das internações atribuíveis (US$ 292) situou-se 36% acima das não-atribuíveis. As doenças vasculares periféricas apresentaram a maior diferença no valor médio entre hospitalizações atribuíveis e não-atribuíveis (24%), porém as cardiovasculares destacaram-se em quantidade (27%) e envolveram os maiores gastos (37%). Os homens internaram menos (48%) que as mulheres, porém com gasto total maior (53%). As internações de pacientes entre 45-64 anos constituíram o maior grupo (45%) e gastos (48%) enquanto os pacientes com ≥75, os maiores coeficientes de hospitalização (350/104hab.) e de despesa (US$ 93,4 mil/104hab.). As regiões mais desenvolvidas gastaram o dobro (/104hab.) em relação às demais. Considerações Finais e Recomendações: As configurações no consumo de serviços hospitalares foram semelhantes às de países mais desenvolvidos, com importantes desigualdades regionais e de sexo. O gasto governamental exclusivamente com hospitalizações atribuíveis ao DM foi expressivo (2,2% do orçamento do Ministério da Saúde). A ampliação de atividades preventivas poderia diminuir a incidência do DM, reduzir a necessidade de internações, minimizar as complicações e minorar a severidade de outras condições médicas mais gerais.

A utilização de serviços odontológicos entre crianças e fatores associados em Sobral, Ceará, Brasil

NORO, L. R. A. et al. A utilização de serviços odontológicos entre crianças e fatores associados em Sobral, Ceará, Brasil. Cad. Saúde Pública, v. 24, n. 7, p. 1509-1516. 2008. ISSN 0102-311X.

Impacto da estratégia saúde da família com equipe de saúde bucal sobre indicadores de saúde bucal: análise em municípios do nordeste com mais de 100 mil habitantes

This study examined in municipalities of Northeast of Brazil with more than one hundred thousand people who incorporation of Oral Health Teams (OHT) into the Family Health Strategy (FHE) the possible impact on oral health indicators. Sought to answer whether implementation OHT brought the best indicators of health problems and coverage, compared to areas without coverage by the FHE through a community trial in parallel, quasi-randomized. In each of the municipalities surveyed were 20 census tracts, 10 were located in areas covered by oral health teams in the ESF and 10 industries in areas not covered. The final sample consisted of 59.221 individuals. We compared oral health indicators related to health problems, access to services and coverage of oral health actions. The analysis strategy was based on the calculation of prevalence ratios and confidence intervals, adjusted for confounding factors through Poisson regression with robust variance. It also has measured the association between an indicator of social inequality for comparison between areas. The best results are associated with indicators of access and coverage of oral health actions at the expense of the indicators of health problems, suggesting a possible maintenance of a traditional model of practice yet. The results also suggest a possible effect of a specific policy in the area of primary care on inequality in access. From the discussions presented throughout this work, we can see that the impact analysis of public policy, obtained by comparing areas with and without the intervention, not only captures the effect on the target population, but other dimensions of organization service and therefore should be understood as one of the analytical possibilities related to the management

Comparative toxicity of antifouling compounds on the development of sea urchin

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

FERRITINA: intervalos de referência para adultos no Estado do Rio Grande do Norte

Ferritin is a protein composed of heavy and light chains, non-covalently linked and which accommodates, in its core, thousands of atoms of iron. Furthermore, this protein represents the stock of iron in the body and it is characterized as an acute marker and predictor of diseases, such as iron deficiency anemia, hereditary hemochromatosis and others. Considering the variability of reference values and the analytical methods currently available, the aim of this work was to propose 95% confidence intervals for adults in the State of Rio Grande do Norte, Brazil, after determining the average concentration of serum ferritin for both sexes, beyond its correlation with the age. We analyzed 385 blood samples, collected by venipuncture from individuals residing in the State, after 12-14 hours of fast. The populational sample had 169 men and 216 women between 18-59 years old, which filled a questionnaire on socioeconomic, food habits and accounts about previous and current diseases. The sample collections were itinerant and the results of erythrogram, fasting glucose, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, urea, creatinine, leukocyte count and platelets, beyond C-reactive protein, were issued to each participant, so that, after selection of the apparently healthy individuals, the dosage of serum ferritin was carried out. Statistical analysis was performed using the softwares SPSS 11.0 Windows version, Epi Info 3.3.2 and Graf instant pad (version 3.02), and the random population sample was single (finite population), for which the test of linear correlation and diagram of dispersion were also made. After selection of individuals and determination of serum ferritin, the most discrepant outliers were disregarded (N = 358, Men = 154/Women = 207) and the average value determined for the masculine sex individuals was 167,18 ng / dL; for the feminine sex individuals, the average value obtained was 81,55 ng / dL. Moreover, we found that 25% of men had values < 90,30 ng / dL; 50% ≤ 156,25 ng / dL and 75% ≤ 229,00 ng / dL. In the group of women, 25% had values < 38,80 ng / dL; 50% ≤ 65,00 ng / dL and 75% ≤ 119,00 ng / dL. Through the correlation coefficient (r = 0,23 with p = 0,003), it is possible to suggest the existence of positive linear correlation between age and serum ferritin for men. The correlation coefficient for women (r = 0,16 with p = 0,025) also confirms the existence of positive linear correlation between serum ferritin and age. Considering the analysis carried out and specific methods corroborating with the proposed benchmarks, we concluded that the average value found for men is higher than that found for women. Furthermore, this scenario rises with age for both sexes, and the 95% confidence intervals obtained were 74 ng/dL ≤ μ ≤ 89 ng/dL and 152ng/dL ≤ μ ≤183ng/dL for the feminine and masculine sex individuals respectively

Aluminum tolerance on genotypes of signal grass

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Determination of Merremia cissoides leaf area using the linear measures of the leaflets

O conhecimento da área foliar de plantas daninhas pode auxiliar o estudo das relações de interferência entre elas e as culturas agrícolas. O objetivo desta pesquisa foi determinar uma equação matemática que estime a área foliar de Merremia cissoides, a partir da relação entre as dimensões lineares dos limbos foliares. Folhas da espécie foram coletadas de diferentes locais na Universidade Estadual Paulista, Jaboticabal, Estado de São Paulo, Brasil, medindo-se o comprimento (C), a largura máxima (L) e a área foliar de três tipos de folíolos. Foram estimadas equações lineares Y = a x (X) para cada tipo de folíolo. Houve sobreposição dos intervalos de confiança das equações dos folíolos primário e secundário, por isso considerou-se uma única equação da média desses folíolos, além da equação do folíolo principal, para caracterização da área foliar de M. cissoides. Assim, a área foliar dessa espécie pode ser estimada pelo somatório das áreas dos limbos foliares dos folíolos principal e primário + secundário, por meio da equação AFnest = 0,501 x (X) + 2,181 x (Z), em que X indica C x L do folíolo principal e Z indica C x L médios dos folíolos primário + secundário, respectivamente.

Precisão da técnica de absorciometria de raios-x de dupla energia na determinação da composição corporal em gatos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)