Comparison of profile-likelihood-based confidence intervals with other rank-based methods for the two-sample problem in ordered categorical data.

For ordered categorical data from randomized clinical trials, the relative effect, the probability that observations in one group tend to be larger, has been considered appropriate for a measure of an effect size. Although the Wilcoxon-Mann-Whitney test is widely used to compare two groups, the null hypothesis is not just the relative effect of 50%, but the identical distribution between groups. The null hypothesis of the Brunner-Munzel test, another rank-based method used for arbitrary types of data, is just the relative effect of 50%.

Longitudinal analysis of pre- and post-treatment measurements with equal baseline assumptions in randomized trials.

For continuous variables of randomized controlled trials, recently, longitudinal analysis of pre- and posttreatment measurements as bivariate responses is one of analytical methods to compare two treatment groups. Under random allocation, means and variances of pretreatment measurements are expected to be equal between groups, but covariances and posttreatment variances are not. Under random allocation with unequal covariances and posttreatment variances, we compared asymptotic variances of the treatment effect estimators in three longitudinal models.

Trends in smoking and lung cancer mortality in Japan, by birth cohort, 1949-2010.

Objective: To determine smoking trends in Japan in comparison with lung cancer mortality.

Methods: Age-specific smoking prevalence among cohorts born between 1897 and 1985 were determined for the period 1949-2010. The percentages of the cohorts born between 1893 and 1979 who initiated smoking early (e.

Impacts of early smoking initiation: long-term trends of lung cancer mortality and smoking initiation from repeated cross-sectional surveys in Great Britain.

Objective: To show long-term trends of smoking initiation in Great Britain including unanalysed data and assess the impact of early smoking initiation on the lung cancer mortality in later ages focusing on birth cohorts.

Design: Reanalysis of repeated cross-sectional surveys conducted 13 times during 1965-1987.

Setting: Great Britain.

Dose-response relationship from longitudinal data with response-dependent dose modification using likelihood methods.

In some clinical trials or clinical practice, the therapeutic agent is administered repeatedly, and doses are adjusted in each patient based on repeatedly measured continuous responses, to maintain the response levels in a target range. Because a lower dose tends to be selected for patients with a better outcome, simple summarizations may wrongly show a better outcome for the lower dose, producing an incorrect dose-response relationship. In this study, we consider the dose-response relationship under these situations.

Analysis of covariance with pre-treatment measurements in randomized trials under the cases that covariances and post-treatment variances differ between groups.

When primary endpoints of randomized trials are continuous variables, the analysis of covariance (ANCOVA) with pre-treatment measurements as a covariate is often used to compare two treatment groups. In the ANCOVA, equal slopes (coefficients of pre-treatment measurements) and equal residual variances are commonly assumed. However, random allocation guarantees only equal variances of pre-treatment measurements.

An estimation method of the clearance for a one-compartment model of a single bolus intravenous injection by a single sampling.

In clinical trials, sometimes only a single drug concentration can be measured from a patient, because of the burden on the patient. From a single concentration, we cannot generally obtain point estimates of each pharmacokinetic parameter in a patient. In this article, we propose a method to estimate the clearance using a one-compartment model of a single-bolus intravenous injection from a single concentration at a sampling point between 1.

An autoregressive linear mixed effects model for the analysis of unequally spaced longitudinal data with dose-modification.

The assessment of the dose-response relationship is important but not straightforward when the therapeutic agent is administered repeatedly with dose-modification in each patient and a continuous response is measured repeatedly. We recently proposed an autoregressive linear mixed effects model for such data in which the current response is regressed on the previous response, fixed effects, and random effects. The model represents profiles approaching each patient's asymptote, takes into account the past dose history, and provides a dose-response relationship of the asymptote as a summary measure.

Analysis of covariance with pre-treatment measurements in randomized trials: comparison of equal and unequal slopes.

In randomized trials, an analysis of covariance (ANCOVA) is often used to analyze post-treatment measurements with pre-treatment measurements as a covariate to compare two treatment groups. Random allocation guarantees only equal variances of pre-treatment measurements. We hence consider data with unequal covariances and variances of post-treatment measurements without assuming normality.

Association between autism and variants in the wingless-type MMTV integration site family member 2 ( WNT2) gene.

Autism is a severe neurodevelopmental disorder with a complex genetic aetiology. The wingless-type MMTV integration site family member 2 (WNT2) gene has been considered as a candidate gene for autism. We conducted a case-control study and followed up with a transmission disequilibrium test (TDT) analysis to confirm replication of the significant results for the first time.

Screening method for severe sleep-disordered breathing in hypertensive patients without daytime sleepiness.

The high prevalence of sleep-disordered breathing (SDB) in hypertensive patients has been well studied. However, regular screening of SDB in these patients is not performed routinely as the diagnostic procedures are both time-consuming and labour-intensive. Overnight portable device screening is useful, but is sometimes not acceptable for asymptomatic SDB patients.

A bivariate autoregressive linear mixed effects model for the analysis of longitudinal data.

In clinical studies, dependent bivariate continuous responses may approach equilibrium over time. We propose an autoregressive linear mixed effects model for bivariate longitudinal data in which the current responses are regressed on the previous responses of both variables, fixed effects, and random effects. The equilibria are modeled using fixed and random effects.

Changes in body mass index by birth cohort in Japanese adults: results from the National Nutrition Survey of Japan 1956-2005.

Background: The National Nutrition Survey, Japan (NNS-J) provides annual anthropometric information for a whole nation over 50 years. Based on this survey, the mean body mass index (BMI) of Japanese men and elderly women has increased in recent decades, but that of young women has decreased. We examined the effect of birth cohort on this phenomenon.

An autoregressive linear mixed effects model for the analysis of longitudinal data which include dropouts and show profiles approaching asymptotes.

We are interested in longitudinal data of a continuous response that show profiles with an initial sharp change and approaching asymptotes for each patient, and many patients drop out with a reason related to the response. In this paper, we focus on a model that assumes a dropout process is missing at random (MAR). In this dropout process, we can obtain consistent maximum likelihood estimators as long as both the mean and covariance structures are correctly specified.

Do overweight children necessarily make overweight adults? Repeated cross sectional annual nationwide survey of Japanese girls and women over nearly six decades.

Objective: To compare growth curves of body mass index from children to adolescents, and then to young adults, in Japanese girls and women in birth cohorts born from 1930 to 1999.

Design: Retrospective repeated cross sectional annual nationwide surveys (national nutrition survey, Japan) carried out from 1948 to 2005.

Setting: Japan.

Association of the neuronal cell adhesion molecule (NRCAM) gene variants with autism.

Autism is a severe neurodevelopmental disorder of early childhood. Genetic factors play an important role in the aetiology of the disorder. In this study, we considered the NRCAM gene as a candidate gene of autism.

An estimation method of the half-life for a one-compartment model of a single bolus intravenous injection by a single sampling.

In clinical trials, sometimes only a single drug concentration can be measured from a patient because of the patient's burden. In this case, the sampling point is usually identical for all patients. From a single concentration, we cannot generally obtain point-estimates of each pharmacokinetic parameter.

The bayesian bias correction method of the first-order approximation of nonlinear mixed-effects models for population pharmacokinetics.

Population pharmacokinetic analysis usually employs nonlinear mixed-effects models. To estimate the parameters, Beal and Sheiner (1982) proposed the first-order method that employs a first-order Taylor series expansion around the means of random individual parameters. Because of the small computational burden and the high convergence proportion of maximization of the log likelihood function, this method is often used in practice.

No association between the neuronal pentraxin II gene polymorphism and autism.

Autism (MIM 209850) is a neurodevelopmental disorder characterized by difficulties with verbal and non-verbal communication, impairments in reciprocal social interactions, and displays of stereotypic behaviors, interests and activities. Twin and family studies have indicated a robust role of genetic factors in the development of autism. Neuronal Pentraxin II (NPTX2) is located in chromosome 7q21.

Tachykinin 1 (TAC1) gene SNPs and haplotypes with autism: a case-control study.

Autism (MIM 209850) is a severe neurodevelopmental disorder characterized by disturbances in social interaction and communication, by repetitive body movements and restricted interests, and by atypical language development. Several twin and family studies have shown strong evidence for genetic factors in the etiology of autism. Glutamate is a major excitatory neurotransmitter in the human brain.

An autoregressive linear mixed effects model for the analysis of longitudinal data which show profiles approaching asymptotes.

In longitudinal data, a continuous response sometimes shows a profile approaching an asymptote. For such data, we propose a new class of models, autoregressive linear mixed effects models in which the current response is regressed on the previous response, fixed effects, and random effects. Asymptotes can shift depending on treatment groups, individuals, and so on, and can be modelled by fixed and random effects.

Profile likelihood-based confidence intervals using Monte Carlo integration for population pharmacokinetic parameters.

Population pharmacokinetic (PPK) analysis usually employs nonlinear mixed effects models using first-order linearization methods. It is well known that linearization methods do not always perform well in actual situations. To avoid linearization, the Monte Carlo integration method has been proposed.

No association of FOXP2 and PTPRZ1 on 7q31 with autism from the Japanese population.

Autism is a child-onset pervasive developmental disorder, with a significant role of genetic factors in its development. Genome-wide linkage studies have suggested a 7q region as a susceptibility locus for autism. We investigated several single nucleotide polymorphisms (SNPs) of Forkhead Box P2 (FOXP2) and Protein-Tyrosine Phosphatase, Receptor-type, Zeta-1 (PTPRZ1) at the 7q region in Japanese patients with autism and healthy controls.