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Effect of aggregation of horn fly populations within cattle herds and consequences for sampling to obtain unbiased estimates of abundance.

Reanalysis of counts of horn fly, Hematobia irritans (L.), obtained from a variety of cattle herds indicated that aggregation of the flies within herds decreased as mean fly density increased. Aggregation was also related to the proportion of fly-resistant and fly-susceptible cattle in a herd. Herds were grouped according to their degree of horn fly aggregation. Low aggregation herds included larger framed Angus, Horned Hereford, Polled Hereford, and Red Poll breeds. Moderate aggregation occurred with Brahman, Charolais, small-framed Angus, mixed cows, and Hereford x Charolais cross. High aggregation occurred with Chianina and mixed herds. Relationships between the sample means and variances varied among aggregation groups. A resampling approach was used to determine the influence of random sampling of a herd on the proportion of horn fly population estimates within fixed percentages of the true mean. The proportion of sample means within +/- 5, 10, 15, and 20% of the true means varied with the proportion of the herd sampled, the mean and variance of fly density, and herd size. Recommendations for obtaining sample size to estimate fly density within a fixed percentage of the true mean are given.

Alberta↗

Atherosclerotic renovascular disease: medical therapy versus medical therapy plus renal artery stenting in preventing renal failure progression: the rationale and study design of a prospective, multicenter and randomized trial (NITER).

BACKGROUND: Many studies suggest a major prevalence of atherosclerotic renovascular disease (ARVD), caused by mono or bilateral renal artery stenosis (RAS). Unfortunately, there is no definite therapy to cure this disease to date; therefore, ARVD is burdened by important clinical complications with high social and economic costs. The last few years have seen important advancements in both medical therapy and in interventional radiology (for example, percutaneous transluminal renal artery stenting (PTRS)). All of them could affect, in some way, the natural history of ARVD, but to date the optimal strategy has not been established. METHODS: The protocol of a prospective, multicenter, randomized trial "Nephropathy Ischemic Therapy (NITER)" is presented. It enrolls patients with stable renal failure (glomerular filtration rate (GFR) >or=30 ml/min) and hypertension, and hemodynamically significant atherosclerotic ostial RAS (>or=70%) diagnosed by duplex Doppler (DD) ultrasonography and confirmed by magnetic resonance angiography (MRA). This study aims to evaluate whether medical therapy plus interventional PTRS is superior to medical therapy alone according to the following combined primary endpoint: death or dialysis initiation or reduction by >20% in estimated GFR after 0.5, 1, and 2 yrs of follow-up and an extended follow-up until the 4th year. Medical therapy means drugs to control hypertension, improve dyslipidemia and optimize platelet anti-aggregant therapy. The sample size is estimated in 50 patients per group to achieve a statistical significance of 0.05 in case of a reduction by 50% in the combined endpoints.

Aged↗

An adjustment to improve the bivariate survivor function repaired NPMLE.

We recently proposed a representation of the bivariate survivor function as a mapping of the hazard function for truncated failure time variates. The representation led to a class of estimators that includes van der Laan's repaired nonparametric maximum likelihood estimator (NPMLE) as an important special case. We proposed a Greenwood-like variance estimator for the repaired NPMLE but found somewhat poor agreement between the empirical variance estimates and these analytic estimates for the sample sizes and bandwidths considered in our simulation study. The simulation results also confirmed those of others in showing slightly inferior performance for the repaired NPMLE compared to other competing estimators as well as a sensitivity to bandwidth choice in moderate sized samples. Despite its attractive asymptotic properties, the repaired NPMLE has drawbacks that hinder its practical application. This paper presents a modification of the repaired NPMLE that improves its performance in moderate sized samples and renders it less sensitive to the choice of bandwidth. Along with this modified estimator, more extensive simulation studies of the repaired NPMLE and Greenwood-like variance estimates are presented. The methods are then applied to a real data example.

Likelihood Functions↗

Inactivated hepatitis A vaccine: long-term antibody persistence.

During the clinical development of safe, well tolerated and immunogenic vaccines against hepatitis A the persistence of protective antibodies was estimated, based on relatively short observation periods of 18 months to 3 years. We report here on longterm persistence of antibodies in volunteers who participated in one of the early clinical trials on inactivated hepatitis A candidate vaccines. In a randomized trial three groups of altogether 110 healthy adults, initially hepatitis A virus (HAV) seronegative persons were vaccinated with an inactivated hepatitis A vaccine according to the schedule 0-1-2-12 months. One group received 180 ELISA units, one group 360, and one 720 ELISA units per dose. Blood samples were taken prior to the first vaccination and at months 1, 2, 3, 4, 6, 12, 13, 18, 24, 36 and 84. The decrease of antibodies was characterized by two disappearance rates: a rapidly decreasing component and a slower decreasing one becoming predominant ca 12 months after booster vaccination. The disappearance of antibodies could be described by a two-component model which holds for t > or = 13 months. The estimated disappearance rates for the slow component (annual decrease) was found to be 11 and 13% for the 180 and 360 El. U groups, respectively (the 720 El. U group showed no decline, which was probably due to the small sample size). The estimated persistence of antibodies within protective range varied between 24 and 47 years depending on individual titres reached at month 13 and vaccination dose.

Adult↗

A case-control study of the relationships among silica exposure, gastric cancer, and esophageal cancer.

BACKGROUND: We examined the effect of silica exposure on gastric and esophageal cancer mortality using a cancer control series in a population setting. METHODS: Cases and controls were restricted to male subjects and were drawn from death certificates in the Tobi area of Japan. A control group was selected from a series of deaths due to colon cancer, and cancers of other organs. The Japanese death certificate system is comprehensive because all deaths must be reported to the local office and death certificates are written by medical doctors. Age and smoking habits adjusted the Mantel-Haenszel odds ratios were estimated. RESULTS: For gastric cancer, the age-, smoking-adjusted odds ratios were 1.22 (95% CI 0.74-2.01) for colon cancer and the other cancer control for silica exposure work, and 1. 36 (95% CI 0.76-2.43) for silicosis. For esophageal cancer, the age- and smoking-adjusted odds ratios were 1.53 (95% CI 0.59-3.96) for the cancer control for silica exposure, and 2.33 (95% CI 0.87-6.23) for silicosis, respectively. CONCLUSIONS: The results suggest that gastric and esophageal cancer were related to silica exposure and silicosis in the study area, although they did not reach a statistically significant level because of the small sample size. The estimated odds ratios were higher for esophageal cancer and silicotic patients.

Adult↗

Controversy of oral contraceptives and risk of rheumatoid arthritis: meta-analysis of conflicting studies and review of conflicting meta-analyses with special emphasis on analysis of heterogeneity.

The authors analyze the heterogeneity present in the combined results of past observational studies that investigated the association between oral contraceptive use and rheumatoid arthritis. The authors also evaluate discrepancies among meta-analyses that focus on the same relation. Of the 15 initially reviewed studies, 10 were selected for this meta-analysis, which also includes a qualitative summary of study characteristics and a critical appraisal of study quality. The authors used the direct method to combine the study results when there was no evidence of heterogeneity and the DerSimonian-Laird method when heterogeneity was present. Using a meta-regression to assess the sources of heterogeneity, the authors weighted summary estimates by sample size and undertook a sensitivity analysis. There was a strong indication of heterogeneity when combining all studies (x2 = 29.34, p = 0.00060) with the source of controls explaining most of the heterogeneity. The most important factor in explaining the differences among the overall summary estimates given by the meta-analyses is that different effect estimates had been selected for the same studies. There is no conclusive evidence of a protective effect of oral contraceptives on the risk of developing rheumatoid arthritis. Consensus is needed on how meta-analyses of observational studies should be conducted.

Arthritis, Rheumatoid↗

A novel mating system analysis for modes of self-oriented mating applied to diploid and polyploid arctic Easter daisies (Townsendia hookeri).

We have developed a new model for mating system analysis, which attempts to distinguish among alternative modes of self-oriented mating within populations. This model jointly estimates the rates of outcrossing, selfing, automixis and apomixis, through the use of information in the family structure given by dominant genetic marker data. The method is presented, its statistical properties evaluated, and is applied to three arctic Easter daisy populations, one consisting of diploids, the other two of tetraploids. The tetraploids are predominantly male sterile and reported to be apomictic while the diploids are male fertile. In each Easter daisy population, 10 maternal arrays of six progeny were assayed for amplified fragment length polymorphism markers. Estimates, confirmed with likelihood ratio tests of mating hypotheses, showed apomixis to be predominant in all populations (ca. 70%), but selfing or automixis was moderate (ca. 25%) in tetraploids. It was difficult to distinguish selfing from automixis, and simulations confirm that with even very large sample sizes, the estimates have a very strong negative statistical correlation, for example, they are not independent. No selfing or automixis was apparent in the diploid population, instead, moderate levels of outcrossing were detected (23%). Low but significant levels of outcrossing (2-4%) seemed to occur in the male-sterile tetraploid populations; this may be due to genotyping error of this level. Overall, this study shows apomixis can be partial, and provides evidence for higher levels of inbreeding in polyploids compared to diploids and for significant levels of apomixis in a diploid plant population.

Asteraceae↗

Quality, evolution, and clinical implications of randomized, controlled trials on the treatment of lung cancer. A lost opportunity for meta-analysis.

A review of 150 published randomized trials on the treatment of lung cancer showed serious methodological drawbacks. Handling of withdrawals (only 7 trials had no dropouts), a priori estimates of sample size (only 9 trials specified the required number of patients), blinding of randomization (only 22 trials had a satisfactory procedure), and information on eligible nonrandomized patients (only 13 studies reported it precisely) were areas of major concern. Although trial quality improved over time both in design/execution (study size estimation and analysis by prognostic factors became more frequent) and reporting (information on patients' characteristics and side effects were more thoroughly reported), their evolution was inconsistent. For non-small-cell lung cancer-despite the persistent lack of proof of efficacy of any active treatment-an untreated control arm was prematurely abandoned and a wide variety of tested regimens prevailed even in better-quality studies. Slightly more promising is the picture for small-cell lung cancer, where research indicates somewhat more reliable-though limited-progress. While clinical research in lung cancer has contributed little to defining the best standard care, we conclude that its heterogeneity makes it unlikely that quantitative meta-analysis of existing trials will be constructive.

Combined Modality Therapy↗

Confidence intervals for genotype relative risks and allele frequencies from the case parent trio design for candidate-gene studies.

OBJECTIVES: Confidence intervals for genotype relative risks, for allele frequencies and for the attributable risk in the case parent trio design for candidate-gene studies are proposed which can be easily calculated from the observed familial genotype frequencies. METHODS: Likelihood theory and the delta method were used to derive point estimates and confidence internals. We used Monte Carlo simulations to show the validity of the formulae for a variety of given modes of inheritance and allele frequencies and illustrated their usefulness by applying them to real data. RESULTS: Generally these formulae were found to be valid for 'sufficiently large' sample sizes. For smaller sample sizes the estimators for genotype relative risks tended to be conservative whereas the estimator for attributable risk was found to be anti-conservative for moderate to high allele frequencies. CONCLUSIONS: Since the proposed formulae provide quantitative information on the individual and epidemiological relevance of a genetic variant they might be a useful addition to the traditional statistical significance level of TDT results.

Alleles↗

Depression and immunity: a meta-analytic review.

A meta-analysis indicated that clinical depression was associated with several large alterations in cellular immunity. Analyzing only methodologically sound studies, reliable immune alterations included lowered proliferative response of lymphocytes to mitogens (effect size rs = .24-.45), lowered natural killer cell activity (r = .28), and alterations in numbers of several white blood cell populations (rs = .11-.77). Immune alterations were greater in both older and hospitalized samples. There was also evidence of a linear relation between intensity of depressive affect and indicators of cellular immunity. Estimates of sample sizes needed to detect reliable effects for each immune outcome are provided. How neuroendocrine mechanisms or health practices might link depression to immunity is discussed, and design features needed to better understand these pathways are specified.

Adult↗

Intraclass correlation coefficients from three cluster randomised controlled trials in primary and residential health care.

OBJECTIVE: This paper provides intraclass correlation coefficients (ICCs) for estimation of sample size inflation required in future cluster randomised trials in primary or residential care. METHODS: Three cluster randomised trials were conducted among middle-aged and older adults in primary care and residential care in Australia and New Zealand between 1995 and 2002. Baseline means or proportions, mean change, and ICCs with their standard errors and 95% confidence intervals are reported for outcome variables used in the three studies. The ICCs were estimated from a one-way random effects model using the analysis of variance method. RESULTS: ICCs for quality of life and psychological variables in the primary care studies were low (below 0.018). ICCs for clinical and physical activity variables ranged from 0 to 0.08. ICCs for health and functional status in residential care for the elderly were high, ranging from 0.025 to 0.514. CONCLUSIONS: The magnitude of the intraclass correlation varies with the venue of the trial, the outcome variables used, and the expected effect of the intervention. However, the intraclass correlations provided will be useful for more appropriate planning of residential and primary care-based trials in the future.

Adult↗

Empirical comparisons of proportional hazards and logistic regression models.

We compare parameter estimates from the proportional hazards model, the cumulative logistic model and a new modified logistic model (referred to as the person-time logistic model), with the use of simulated data sets and with the following quantities varied: disease incidence, risk factor strength, length of follow-up, the proportion censored, non-proportional hazards, and sample size. Parameter estimates from the person-time logistic regression model closely approximated those from the Cox model when the survival time distribution was close to exponential, but could differ substantially in other situations. We found parameter estimates from the cumulative logistic model similar to those from the Cox and person-time logistic models when the disease was rare, the risk factor moderate, and censoring rates similar across the covariates. We also compare the models with analysis of a real data set that involves the relationship of age, race, sex, blood pressure, and smoking to subsequent mortality. In this example, the length of follow-up among survivors varied from 5 to 14 years and the Cox and person-time logistic approaches gave nearly identical results. The cumulative logistic results had somewhat larger p-values but were substantively similar for all but one coefficient (the age-race interaction). The latter difference reflects differential censoring rates by age, race and sex.

Adolescent↗

A maximum likelihood algorithm for genome mapping of cytogenetic loci from meiotic configuration data.

Frequencies of meiotic configurations in cytogenetic stocks are dependent on chiasma frequencies in segments defined by centromeres, breakpoints, and telomeres. The expectation maximization algorithm is proposed as a general method to perform maximum likelihood estimations of the chiasma frequencies in the intervals between such locations. The estimates can be translated via mapping functions into genetic maps of cytogenetic landmarks. One set of observational data was analyzed to exemplify application of these methods, results of which were largely concordant with other comparable data. The method was also tested by Monte Carlo simulation of frequencies of meiotic configurations from a monotelodisomic translocation heterozygote, assuming six different sample sizes. The estimate averages were always close to the values given initially to the parameters. The maximum likelihood estimation procedures can be extended readily to other kinds of cytogenetic stocks and allow the pooling of diverse cytogenetic data to collectively estimate lengths of segments, arms, and chromosomes.

Algorithms↗

An international multicenter protocol to assess the single and combined benefits of antiemetic interventions in a controlled clinical trial of a 2x2x2x2x2x2 factorial design (IMPACT).

For various diseases clinicians have to combine different drugs or interventions when a single drug or intervention does not lead to satisfactory results. However, quantifying the relative benefit of certain drugs or interventions when given alone and in combination under controlled conditions requires a complex factorial design. This paper describes such a method applied to a large multicenter trial for the prevention of postoperative nausea and vomiting (PONV), which may be of great interest for other specialties. Approximately 28 million operations are performed annually in the United States, mainly under general anesthesia with volatile anesthetics. Unfortunately, one-third of these patients suffer from PONV. This prompted extensive research of antiemetic and anesthetic drugs, but none of the interventions appeared to satisfactorily prevent PONV. Scuderi et al. were the first to almost eliminate PONV by combining various antiemetic interventions; however, the relative benefit of each intervention remained unclear. Accordingly, we have designed a large randomized controlled trial studying six different antiemetic interventions-three involving use of various antiemetic drugs and three involving choice of anesthetic drugs-to answer the following main questions: (1) What is the relative benefit of each of the antiemetic intervention? (2) Are certain combinations of antiemetic interventions more effective than others? Using a complete factorial design this leads to 2(3)=8 antiemetic combinations, which multiply with the 2(3)=8 combinations of anesthetic drugs, leading to a total of 2(6)=64 possible combinations. The six factors are the antiemetics ondansetron (versus control), dexamethasone (versus control), droperidol (versus control), and the intravenous anesthetic propofol (versus volatile anesthetics), air (versus nitrous oxide), and remifentanil (versus fentanyl). The primary outcome is freedom from PONV within the first 24 hours after anesthesia. Eligible patients are adults scheduled for elective surgery under general anesthesia with an increased risk for PONV so that the expected incidence in the control group (with none of the six antiemetic interventions) is approximately 60%. In order to allow analyses for up to three factor interactions, a sample size was estimated to be in the range of approximately 5000 patients. To the best of our knowledge this is the first randomized controlled trial of a six-way factorial design that may serve as an example for numerous other medical specialties.

Anesthesia, Inhalation↗

Sample size planning for the standardized mean difference: accuracy in parameter estimation via narrow confidence intervals.

Methods for planning sample size (SS) for the standardized mean difference so that a narrow confidence interval (CI) can be obtained via the accuracy in parameter estimation (AIPE) approach are developed. One method plans SS so that the expected width of the CI is sufficiently narrow. A modification adjusts the SS so that the obtained CI is no wider than desired with some specified degree of certainty (e.g., 99% certain the 95% CI will be no wider than omega). The rationale of the AIPE approach to SS planning is given, as is a discussion of the analytic approach to CI formation for the population standardized mean difference. Tables with values of necessary SS are provided. The freely available Methods for the Behavioral, Educational, and Social Sciences (K. Kelley, 2006a) R (R Development Core Team, 2006) software package easily implements the methods discussed.

Confidence Intervals↗

An introduction to statistical inference--3.

Statistics inference is used to make comments about a population based upon data from a sample. In a similar manner it can be applied to a population to make an estimate about a sample. It is commonly seen in medical publications when the null hypothesis is being tested. This calculates the probability (p value) of a type I error--that is, that a particular finding is attributable to chance. It is also important to be aware of the chances of a type II error--that is, accepting the null hypothesis when it does not apply. Sample size, point estimate and variability are common factors that will affect the chances of making these two types of errors. Interpreting results therefore needs to take these factors into account as well as the clinical relevance of the findings. Statistical significance does not necessarily mean clinical significance.

Emergency Service, Hospital↗

Variability in the measurement of nebulized aerosol deposition in man.

1. This study was performed to determine the variability of two different scintigraphic methods of measuring pulmonary aerosol deposition, and to examine nebulizer particle size and drug output as potential sources of this variability. 2. A radioaerosol was produced from a 3 ml solution of 99mTc-labelled colloidal human serum albumin (0.05 mg, 37 MBq) using a standard jet nebulizer and air compressor. This was inhaled on three separate occasions by nine healthy male subjects. One one of these occasions, a further inhalation was performed to assess immediate repeatability using increased 99mTc activity (92 MBq). 3. Intrapulmonary aerosol deposition was measured with a gamma-camera and was corrected for tissue attenuation and geometric distribution by using two different methods. 4. Estimated mean pulmonary deposition was 4.3% of the nebulizer dose using a lung phantom correction method, and 6.1% using a tissue attenuation method. For these two methods respectively variability between subjects (coefficient of variation) was 54 and 47%. For both methods, within-subject variability (coefficient of variation) was 37% between occasions and 23% within occasions. 5. The particle-size output of several nebulizers was highly reproducible (coefficient of variation less than 4%), but the nebulizer mass and radionuclide output of two nebulizers was more variable (coefficient of variation 5-19%), and appeared to be an important contributor to the variability in pulmonary aerosol deposition. 6. The data presented here for pulmonary deposition, used with appropriate power statistics formulae, can be used to estimate the sample sizes required for comparative studies of lung aerosol deposition.

Aerosols↗

Within-plant distribution and sampling of single and mixed infestations of Bemisia tabaci and Trialeurodes vaporariorum (Homoptera: Aleyrodidae) in winter tomato crops.

In several areas of Spain, the greenhouse whitefly, Trialeurodes vaporariorum (Westwood), and the sweet potato whitefly, Bemisia tabaci (Gennadius), coexist in tomato, Lycopersicon esculentum Miller. For integrated pest management decision-making, it is important to know the abundance of each species, because they exhibit different abilities to transmit viruses, are susceptible to different biological control agents, and have different responses to insecticides. This study was conducted to provide information on the vertical distribution of T. vaporariorumn and B. tabaci in tomato plants grown in greenhouses in winter and to determine the optimal sampling unit and the sample size for estimating egg and nymphal densities of both whitefly species. Eggs of T. vaporariorum were mainly located on the top stratum of the plant, whereas B. tabaci eggs were mainly found on the middle stratum. Nymphs of both species mainly concentrated in the bottom stratum of the plant. When pest abundance and low relative variation were considered, the bottom stratum was selected as the most convenient for sampling nymphs of both whitefly species. Conversely, the same two criteria indicated that either the top or the middle strata could be used when sampling T. vaporariorum and B. tabaci eggs. Several different sampling units were compared to optimize the estimation of nymphal and egg densities in terms of cost efficiency. One disk (1.15 cm in diameter) per leaflet collected from the top stratum of the tomato plant was the most efficient sampling unit for simultaneously estimating the egg densities of the two whitefly species.

Animals↗