Genetic progress in homogeneous regions of wheat cultivation in Rio Grande do Sul State, Brazil.

The State of Rio Grande do Sul (RS) stands out as the largest wheat producer in Brazil. Wheat is the most emphasized winter cereal in RS, attracting public and private investments directed to wheat genetic breeding. The study of genetic progress should be performed routinely at breeding programs to study the behavior of cultivars developed for homogeneous regions of cultivation. The objectives of this study were: 1) to evaluate the genetic progress of wheat grain yield in RS; 2) to evaluate the influence of cultivar competition trial stratification in homogeneous regions of cultivation on the study of genetic progress. Grain yield data of 122 wheat cultivars evaluated in 137 trials arranged in randomized block design with three or four replications were used. Field trials were carried out in 23 locations in RS divided into two homogeneous regions during the period from 2002 to 2013. Genetic progress for RS and homogeneous regions was studied utilizing the method proposed by Vencovsky. Annual genetic progress for wheat grain yield during the period of 12 years in the State of RS was 2.86%, oscillating between homogeneous regions of cultivation. The difference of annual genetic progress in region 1 (1.82%) in relation to region 2 (4.38%) justifies the study of genetic progress by homogeneous regions of cultivation.

Genetic progress in sunflower crop in Rio Grande do Sul State, Brazil.

The sunflower has adaptability to growing regions with different climatic and soil characteristics, showing drought tolerance and high-quality oil production. The State of Rio Grande do Sul is the third largest sunflower producer in Brazil, with research related to the sunflower breeding initiated after the decade of 1950. The aim of this study was to evaluate the genetic progress for grain yield, oil content, and oil yield of sunflower (Helianthus annuus L.) in the State of Rio Grande do Sul. Data of grain yield, oil content, and oil yield obtained from 58 sunflower cultivar yield trials in 19 municipalities in Rio Grande do Sul during the period from 2005 to 2014 were used. Genetic progress was studied according to the methodology proposed by Vencovsky and data from sunflower cultivar yield trials were used. Annual genetic progress of sunflower during the period of 10 years (2005-2014) was 132.46 kg⋅ha-1⋅year-1 for grain yield, -0.17%/year for oil content, and 48.11 kg⋅ha-1⋅year-1 for oil yield. The sunflower-breeding programs in the State of Rio Grande do Sul were efficient for the traits grain yield and oil yield and presented no efficiency for oil content.

REML/BLUP and sequential path analysis in estimating genotypic values and interrelationships among simple maize grain yield-related traits.

Methodologies using restricted maximum likelihood/best linear unbiased prediction (REML/BLUP) in combination with sequential path analysis in maize are still limited in the literature. Therefore, the aims of this study were: i) to use REML/BLUP-based procedures in order to estimate variance components, genetic parameters, and genotypic values of simple maize hybrids, and ii) to fit stepwise regressions considering genotypic values to form a path diagram with multi-order predictors and minimum multicollinearity that explains the relationships of cause and effect among grain yield-related traits. Fifteen commercial simple maize hybrids were evaluated in multi-environment trials in a randomized complete block design with four replications. The environmental variance (78.80%) and genotype-vs-environment variance (20.83%) accounted for more than 99% of the phenotypic variance of grain yield, which difficult the direct selection of breeders for this trait. The sequential path analysis model allowed the selection of traits with high explanatory power and minimum multicollinearity, resulting in models with elevated fit (R2 > 0.9 and ε < 0.3). The number of kernels per ear (NKE) and thousand-kernel weight (TKW) are the traits with the largest direct effects on grain yield (r = 0.66 and 0.73, respectively). The high accuracy of selection (0.86 and 0.89) associated with the high heritability of the average (0.732 and 0.794) for NKE and TKW, respectively, indicated good reliability and prospects of success in the indirect selection of hybrids with high-yield potential through these traits. The negative direct effect of NKE on TKW (r = -0.856), however, must be considered. The joint use of mixed models and sequential path analysis is effective in the evaluation of maize-breeding trials.

Sample sizes to estimate mean values for tassel traits in maize genotypes.

Tassel traits are important in maize breeding programs aiming to reduce the size and number of branches and maintain satisfactory pollen production in order to increase grain yield. The objectives of this study were to determine the sample size (number of tassels) required to estimate the mean values for tassel traits in maize genotypes and to verify the variability of sample size among genotypes. Twenty maize genotypes were evaluated in an experiment carried out in a randomized block design with three replicates. Twenty tassels were randomly collected in each plot, for a total of 1200 tassels. In each tassel, the following traits were measured: peduncle dry matter, branching space dry matter, central spike dry matter, tassel dry matter, peduncle length, branching space length, central spike length, tassel length, tassel dry matter to tassel length ratio, number of primary branches, number of secondary branches, and tassel branch number. Measures of central tendency and variability were calculated, analysis of variance and mean comparison tests were performed, normality was verified, and the sample size was determined. In order to estimate the means with the same precision, the sample size for weight traits was greater than that for length traits. For tassel traits, 11, 20, and 43 tassels are sufficient to estimate the mean with a precision of 40, 30, and 20%, respectively, of the estimated mean at a 95% confidence level. These data show that there is sample size variability among maize genotypes.

Genetic progress in oat associated with fungicide use in Rio Grande do Sul, Brazil.

The State of Rio Grande do Sul (RS) is the largest producer of oat in Brazil with the aid of consolidated breeding programs, which are constantly releasing new cultivars. The main objectives of this study were to: 1) evaluate the annual genetic progress in grain yield and hectoliter weight of the oat cultivars in RS, with and without fungicide use on aerial parts of plants; and 2) evaluate the efficiency of oat breeding programs in introducing disease-resistant genes in the released cultivars through network yield trials conducted with and without fungicide use on aerial plant parts. The data on grain yield and hectoliter weight were obtained from 89 competition field trials of oat cultivars carried out from 2007 to 2014 in nine municipalities of RS. Of the total 89 trials, 44 were carried out with fungicide application on aerial plant parts and 45 were carried out without fungicide application. The annual genetic progress in oat cultivars was studied using the methodology proposed by Vencovsky (1988). The annual genetic progress in oat grain yield was 1.02% with fungicide use and 4.02% without fungicide use during the eight-year study period in RS. The annual genetic progress with respect to the hectoliter weight was 0.08% for trials with fungicide use and 0.71% for trials without fungicide use. Performing network yield trials with and without fungicide use on the aerial plants parts is a feasible method to evaluate the efficiency of oat breeding programs in introducing disease-resistant genes in the released cultivars.

Predictors of mortality and mortality from cardiac causes in the bypass angioplasty revascularization investigation (BARI) randomized trial and registry. For the BARI Investigators.

BACKGROUND: The impact of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) on long-term mortality rates in the presence of various demographic, clinical, and angiographic factors is uncertain in the population of patients suitable for both procedures. METHODS AND RESULTS: In the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial and registry, 3610 patients who were eligible to receive PTCA and CABG were revascularized between 1989 and 1992. Multivariate Cox models were used to identify factors associated with 5-year mortality and cardiac mortality, with particular attention to factors that interact with treatment. Diabetic patients receiving insulin had higher mortality and cardiac mortality rates with PTCA compared with CABG (relative risk [RR] 1.78 and 2.63, respectively, P<0.001), and patients with ST elevation had higher cardiac mortality rates with CABG than with PTCA (RR 4.08, P<0.001). Factors most strongly associated with high overall mortality rates were insulin-treated diabetes, congestive heart failure, kidney failure, and older age. Black race was also associated with higher mortality rates (RR 1.49, P=0.019). CONCLUSIONS: A set of variables was identified that could be used to help select a revascularization procedure and to evaluate risk of long-term mortality in the population of patients considering revascularization.

Patients at lower risk of arrhythmia recurrence: a subgroup in whom implantable defibrillators may not offer benefit. Antiarrhythmics Versus Implantable Defibrillator (AVID) Trial Investigators.

OBJECTIVES: The goal of this study was to identify subgroups of arrhythmia patients who do not benefit from use of the implantable cardiac defibrillator (ICD). BACKGROUND: Treatment of serious ventricular arrhythmias has evolved toward more common use of the ICD. Since estimates of the cost per year of life saved by ICD therapy vary from $25,000 to perhaps $125,000, it is important to identify patient subgroups that do not benefit from the ICD. METHODS: Data for 491 ICD patients enrolled in the Antiarrhythmics Versus Implantable Defibrillators Study were used to create a hazards model relating baseline factors to time to first recurrent arrhythmia. The model was used to predict the hazard for recurrent arrhythmia among all trial patients. A priori cut points provided lower and higher recurrent arrhythmia risk strata. For each stratum the incremental years of life due to ICD versus antiarrhythmic drug therapy were calculated. RESULTS: Factors that predicted recurrent arrhythmia were: ventricular tachycardia as the index arrhythmia, history of cerebrovascular disease, lower left ventricular ejection fraction, a history of any tachyarrhythmia before the index event and the absence of revascularization after the index event. Survival times (over a follow-up of three years) were identical in each arm of the lowest risk sextile (survival advantage 0.03 +/- 0.12 [se] years), while the survival advantage for patients above the first sextile was 0.27 +/- 0.07 (se) years (two-sided p = 0.05). CONCLUSIONS: Patients presenting with an isolated episode of ventricular fibrillation in the absence of cerebrovascular disease or history of prior arrhythmia who have undergone revascularization or who have moderately preserved left ventricular function (left ventricular ejection fraction > 0.27) are not likely to benefit from ICD therapy compared with amiodarone therapy.

Beta-blocker use and survival in patients with ventricular fibrillation or symptomatic ventricular tachycardia: the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial.

OBJECTIVES: To evaluate whether use of beta-adrenergic blocking agents, alone or in combination with specific antiarrhythmic therapy, is associated with improved survival in persons with ventricular fibrillation (VF) or symptomatic ventricular tachycardia (VT). BACKGROUND: The ability of beta-blockers to alter the mortality of patients with VF or VT receiving contemporary medical management is not well defined. METHODS: Survival of 1,016 randomized and 2,101 eligible, nonrandomized patients with VF or symptomatic VT followed in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial through December 31, 1996 was assessed using Cox proportional hazards analysis. RESULTS: The 817 (28%) patients discharged from hospital receiving beta-blockers had less ventricular dysfunction, fewer symptoms of heart failure and a different pattern of medication use compared with patients not receiving beta-blockers. Before adjustment for important prognostic variables, beta-blockade was not significantly associated with survival in randomized or in eligible, nonrandomized patients treated with specific antiarrhythmic therapy. After adjustment, beta-blockade remained unrelated to survival in randomized or in eligible, nonrandomized patients treated with amiodarone alone (n = 1142; adjusted relative risk [RR] = 0.96; 95% confidence interval [CI] 0.64-1.45; p = 0.85) or a defibrillator alone (n = 1347; adjusted RR = 0.88; 95% CI 0.55 to 1.40; p = 0.58). In contrast, beta-blockade was independently associated with improved survival in eligible, nonrandomized patients who were not treated with specific antiarrhythmic therapy (n = 412; adjusted RR = 0.47; 95% CI 0.25 to 0.88; p = 0.018). CONCLUSIONS: Beta-blocker use was independently associated with improved survival in patients with VF or symptomatic VT who were not treated with specific antiarrhythmic therapy, but a protective effect was not prominent in patients already receiving amiodarone or a defibrillator.

Prevention and Treatment of Hypertension Study (PATHS): effects of an alcohol treatment program on blood pressure.

OBJECTIVE: To determine whether blood pressure is reduced for at least 6 months with an intervention to lower alcohol intake in moderate to heavy drinkers with above optimal to slightly elevated diastolic blood pressure, and whether reduction of alcohol intake can be maintained for 2 years. DESIGN: A randomized controlled trial. METHODS: Six hundred forty-one outpatient veterans with an average intake of 3 or more alcoholic drinks per day in the 6 months before entry into the study and with diastolic blood pressure 80 to 99 mm Hg were randomly assigned to a cognitive-behavioral alcohol reduction intervention program or a control observation group for 15 to 24 months. The goal of the intervention was the lower of 2 or fewer drinks daily or a 50% reduction in intake. A subgroup with hypertension was defined as having a diastolic blood pressure of 90 to 99 mm Hg, or 80 to 99 mm Hg if recently taking medication for hypertension. RESULTS: Reduction in average weekly self-reported alcohol intake was significantly greater (P<.001) at every assessment from 3 to 24 months in the intervention group vs the control group: levels declined from 432 g/wk at baseline by 202 g/wk in the intervention group and from 445 g/wk by 78 g/wk in the control group in the first 6 months, with similar reductions after 24 months. The intervention group had a 1.2/0.7-mm Hg greater reduction in blood pressure than the control group (for each, P = .17 and P = .18) for the 6-month primary end point; for the hypertensive stratum the difference was 0.9/0.7 mm Hg (for each, P = .58 and P = .44). CONCLUSIONS: The 1.3 drinks per day average difference between changes in self-reported alcohol intake observed in this trial produced only small nonsignificant effects on blood pressure. The results from the Prevention and Treatment of Hypertension Study (PATHS) do not provide strong support for reducing alcohol consumption in nondependent moderate drinkers as a sole method for the prevention or treatment of hypertension.

An overview of randomized trials of sodium reduction and blood pressure.

To test for effects on systolic and diastolic blood pressure and to provide precise estimates of their magnitude, we conducted an overview of randomized clinical trials that aimed to reduce the intake of sodium in human subjects. We excluded from pooled analyses trials with confounded designs, those that compared intake levels beyond the usual range in the population, and those without published reports. Two reviewers abstracted information in duplicate and differences were reconciled. Twenty-three trials with outcome data from an aggregate of 1,536 subjects were included. Data were pooled both separately for hypertensive and normotensive subjects and for all trials combined. With the use of sample size weighting, blood pressure reductions (net of controls) were 4.9 +/- 1.3/2.6 +/- 0.8 mm Hg (systolic and diastolic, respectively, with 95% confidence limits) in hypertensive subjects and 1.7 +/- 1.0/1.0 +/- 0.7 mm Hg in normotensive subjects. The combined blood pressure reductions were 2.9 +/- 0.8/1.6 +/- 0.5 mm Hg. These changes were associated with mean reduction of urinary sodium excretion ranging from 16 to 171 mmol/24 hr for individual trials. A dose-response relation across trials was found, both in normotensive and in hypertensive subjects. These results indicate that sodium reduction lowers mean blood pressure in both hypertensive and normotensive individuals for periods of at least several months. The findings are highly consistent with results of observational epidemiological studies and have implications for preventive strategies of blood pressure control.

Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.

Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors. The "gold standard" glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo, but neither is easily implemented in large studies. Thus, it is of interest to develop a simple, accurate method for assessing insulin sensitivity that is useful for clinical investigations. We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sampled iv glucose tolerance tests on 28 nonobese, 13 obese, and 15 type 2 diabetic subjects. We obtained correlations between indexes of insulin sensitivity from glucose clamp studies (SI(Clamp)) and minimal model analysis (SI(MM)) that were comparable to previous reports (r = 0.57). We performed a sensitivity analysis on our data and discovered that physiological steady state values [i.e. fasting insulin (I(0)) and glucose (G(0))] contain critical information about insulin sensitivity. We defined a quantitative insulin sensitivity check index (QUICKI = 1/[log(I(0)) + log(G(0))]) that has substantially better correlation with SI(Clamp) (r = 0.78) than the correlation we observed between SI(MM) and SI(Clamp). Moreover, we observed a comparable overall correlation between QUICKI and SI(Clamp) in a totally independent group of 21 obese and 14 nonobese subjects from another institution. We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research.

Randomized trials of sodium reduction: an overview.

We updated a previously published overview of randomized clinical trials testing the effects of reducing sodium intake. We excluded trials that had confounded designs, enrolled preadolescent study populations, tested intakes outside the usual range for the US population, or reported neither systolic nor diastolic blood pressure. Thirty-two trials with outcome data for 2635 subjects were included. Two reviewers abstracted information independently and differences were reconciled. Pooled blood pressure differences between treated and control groups were highly significant for all trials combined and for trials in hypertensive and normotensive subjects pooled separately. The effects on blood pressure of lowering sodium in hypertensive and normotensive subjects, respectively (each trial weighted according to sample size), were -4.8/-2.5 and -1.9/-1.1 mm Hg (systolic/diastolic). Median differences in sodium excretion between sodium-reduction and control groups in these subgroups were -77 and -76 mmol/24 h, respectively. Weighted linear-regression analyses across the trials showed dose responses, which were more consistent for trials in normotensive subjects. These associations were, per 100 mmol Na/24 h, -5.8/-2.5 and -2.3/-1.4 mm Hg in hypertensive and normotensive subjects, respectively. There is no evidence that sodium reduction as achieved in these trials presents any safety hazards. The blood pressure reduction that would result from a substantial lowering of dietary sodium in the US population could reduce cardiovascular morbidity and mortality.

Longitudinal analysis of categorical epidemiological data: a study of Three Mile Island.

The accident at the Three Mile Island nuclear power plant in 1979 led to an unprecedented set of events with potentially life threatening implications. This paper focusses on the analysis of a longitudinal study of the psychological well-being of the mothers of young children living within 10 miles of the plant. The initial analyses of the data utilize loglinear/logit model techniques from the contingency table literature, and involve the fitting of a sequence of logit models. The inadequancies of these analyses are noted, and a new class of mixture models for logistic response structures is introduced to overcome the noted shortcomings. The paper includes a brief outline of the methodology relevant for the fitting of these models using the method of maximum likelihood, and then the model is applied to the TMI data. The paper concludes with a discussion of some of the substantive implications of the mixture model analysis.

Variance imputation for overviews of clinical trials with continuous response.

Overviews of clinical trials are an efficient and important means of summarizing information about a particular scientific area. When the outcome is a continuous variable, both treatment effect and variance estimates are required to construct a confidence interval for the overall treatment effect. Often, only partial information about the variance is provided in the publication of the clinical trial. This paper provides heuristic suggestions for variance imputation based on partial variance information. Both pretest-posttest (parallel groups) and crossover designs are considered. A key idea is to use separate sources of incomplete information to help choose a better variance estimate. The imputation suggestions are illustrated with a data set.

Use of preventive interventions by persons infected with type-1 human immunodeficiency virus (HIV-1). The Pulmonary Complications of HIV Study Group.

Measures aimed at preventing complications and slowing progression of type-1 human immunodeficiency virus (HIV-1) can potentially reduce morbidity. Although little is known about the use of such measures, such data are critical for program planning. This study was performed to quantify the frequency and patterns of use for such interventions. We enrolled 1,171 persons infected with HIV, but without an acquired immunodeficiency syndrome (AIDS) defining diagnosis, in a multicenter prospective study of the pulmonary complications of HIV infection. Participants were homosexual/bisexual men, injection drug users (IDUs), or female sexual contacts of HIV-infected men. Centers were university-based and geographically dispersed across the United States. Standardized questionnaires were administered on entry and at three-month or six-month intervals; we correlated use of general and HIV-related preventive measures before entry and during the first three years in study with clinical/epidemiologic characteristics. Overall use of preventive interventions was low; only one third of study entrants had used such measures. Use was greatest among those with advanced HIV infection, but only half used preventive measures on entry; IDUs were less likely than homosexuals to use these services. Although use of interventions such as anti-Pneumocystis and antiretroviral agents increased during study participation, general measures such as pneumococcal vaccine and tuberculosis prophylaxis were used by less than 30% of those eligible for use. Among IDUs, cumulative use of these measures remained below 20% during the first three years of this study. We conclude that HIV-infected persons underuse preventive interventions, particularly general measures.(ABSTRACT TRUNCATED AT 250 WORDS)

Gender differences in the psychosocial variance of Framingham and Bortner Type A measures.

The object of the present study was to determine whether the non-genetic variance of a Type A scale composed of Framingham and Bortner items had gender specific psychosocial components. The study was performed on a group of Swedish twins so that variance explained by heritability for Type A could first be removed from the equation. The overall Type A score had been found to relate to self-reported CHD in this population. The dependent variable was the standardized score residual remaining after removing the genetic variance (i.e., that explained by co-twin score and zygosity). Multiple regression analyses revealed that there were differences in the psychosocial components of the Type A residual in men and women. These results are discussed in terms of culturally accepted gender roles and their possible implications for health endpoints.

Modelling transitional and joint marginal distributions in repeated categorical data.

When a repeated measures endpoint classifies people into several categories, marginal and transitional models provide two distinct approaches for data analysis. Marginal models estimate the probabilities of being in different categories over time. Transitional models estimate the probability of changing between any two given states during follow-up visits. This paper develops transitional and marginal models and applies them to a clinical trial of treatments of opiate addiction. The primary outcome was the presence or absence of opiates in a thrice weekly urine test, administered for 17 weeks. Subjects frequently miss visits, however, and in effect respond in one of three ways to a visit: missing, opiates present or opiates absent. Thus we have three possible states. Our transitional model conditions on the current state and models the transition from state k to one of the other (0, ..., K-1) states using a mutinomial logit model. This model generalizes previous work of Muenz and Rubinstein. Significant covariates in this model are predictive of state changes. Our marginal model views the state at each time point, rather than the transitions, as the primary response. Here we model the probability of being in state k with a multinomial logit model. Correlation within individuals over visits can be handled by applying the approach of Zeger and Liang or the bootstrap. Significant covariates in this model can include more 'global' summaries of a person such as extent of previous opiate use. Both marginal and transitional models are needed to provide a complete description of an individual's behaviour over time since global summaries might not affect transitions. Of particular substantive interest is how the opiate treatments affect both the marginal and transition probabilities.

Multivariate tests for multiple endpoints in clinical trials.

Clinical trials frequently lack a single definitive endpoint that completely describes treatment efficacy. When a treatment affects a disease in a multitude of ways, several endpoints are necessary to describe efficacy. There is a variety of statistical procedures to provide a single p-value when a treatment affects several endpoints. This paper reviews several procedures including Hotelling's T2 test, an approximate likelihood ratio test (Tang et al.), the weighted version of O'Brien's test, tests involving the maximum of several test statistics, and a test based on the average of the maximum of several endpoints (Wittes). I propose a risk score test whose rejection boundary corresponds to a contour of constant risk. Calculations and simulation studies help to compare the different tests with an emphasis on the effect of non-standard alternatives, and on identifying settings where some tests may lack clinical relevance.

The effect of screening on some pretest-posttest test variances.

The clinical trial design in which the endpoint is measured both at baseline and at the end of the study is used in a variety of situations. For two-group designs, test such as the t test or analysis of covariance are commonly used to evaluate treatment efficacy. Often such pretest-posttest trials restrict participation to subjects with a baseline measurement of the endpoint in a certain range. A range may define a disease, or it may be thought that subjects with extreme measurements are more responsive to treatment. This paper examines the effect of screening on the analysis of covariance and t-test variances relative to the population (i.e., unscreened) variances. Bivariate normal and bivariate gamma distributions are assumed for the (pretest, posttest) measurements. Because the sample size required to detect a specified difference between treatment and control is proportional to the variance, the results have direct application to setting sample size.