An approximate marginal logistic distribution for the analysis of longitudinal ordinal data

Subject-specific and marginal models have been developed for the analysis of longitudinal ordinal data. Subject-specific models often lack a population-average interpretation of the model parameters due to the conditional formulation of random intercepts and slopes. Marginal models frequently lack an underlying distribution for ordinal data, in particular when generalized estimating equations are applied. To overcome these issues, latent variable models underneath the ordinal outcomes with a multivariate logistic distribution can be applied. In this article, we extend the work of O'Brien and Dunson (2004), who studied the multivariate t-distribution with marginal logistic distributions. We use maximum likelihood, instead of a Bayesian approach, and incorporated covariates in the correlation structure, in addition to the mean model. We compared our method with GEE and demonstrated that it performs better than GEE with respect to the fixed effect parameter estimation when the latent variables have an approximately elliptical distribution, and at least as good as GEE for other types of latent variable distributions

Statistical process control methods for monitoring in-house reference standards

For certain types of medicine the biological strength or bioactivity of a drug is the main characteristic for release of products to the market. A pharmaceutical company may decide to use their own in-house reference standard to test the drug instead of using the expensive international reference standard. The company is then legally obliged to verify that the in-house reference standard remains stable over time with respect to the international one. This is a special problem within statistical process control (SPC) since the monitoring period is relatively short and bioassays are typically heterogenous. The objective of this article is to apply methods from SPC and dose-finding studies to different study designs and assess how well these methods perform in detecting a decline in bioactivity. The included methods are the exponentially weighted moving average (EWMA), Shewhart chart, and analysis of variance (ANOVA)-type contrasts (linear, Helmert, and reverse-Helmert). An optimal a-spending function was selected first to avoid inflating the familywise error rate. The normal a-spending function seemed to perform generally the best. Then from the results, the linear, reverse-Helmert, and the EWMA (¿ = 0.6) resulted in high power when a change occurred at earlier time points, while Helmert and the EWMA (¿ > 0.6) performed better in later declines. Linear contrasts and the Shewhart chart performed better irrespective of the decline profile. Having more bioassay runs at the beginning of the stability study increased the probability of detecting a decline. If there is no prior information on the expected deterioration profile, linear contrasts or Shewhart chart should be preferred. Otherwise, reverse-Helmert or Helmert contrasts should be chosen for either early or late deterioration, respectively. Keywords: Bioassay, Dose-finding, Familywise error, Quality control, Sequential tests, Stabilit

Equivalence testing for similarity in bioassays using bioequivalence criteria on the relative bioactivity

Similarity in bioassays means that the test preparation behaves as a dilution of the standard preparation with respect to their biological effect. Thus, similarity must be investigated to confirm this biological property. Historically, this was typically conducted with traditional hypothesis testing, but this has received substantial criticism. Failing to reject similarity does not imply that the 2 preparations are similar. Also, rejecting similarity when bioassay variability is small might simply demonstrate a nonrelevant deviation in similarity. To remedy these concerns, equivalence testing has been proposed as an alternative to traditional hypothesis testing, and it has found its way in the official guidelines. However, similarity has been discussed mainly in terms of the parameters in the dose-response curves of the standard and test preparations, but the consequences of nonsimilarity on the relative bioactivity have never been investigated. This article provides a general equivalence approach to evaluate similarity that is directly related to bioequivalence on the relative bioactivity of the standard and test preparations. Bioequivalence on the relative bioactivity can only be guaranteed for positive (only nonblanks) and finite dose intervals. The approach is demonstrated on 4 case studies in which we also show how to calculate a sample size and how to investigate the power of equivalence on similarity

Chronic stress and adolescents’ mental health : modifying effects of basal cortisol and parental psychiatric history. The TRAILS study

Large individual differences in adolescent mental health following chronic psychosocial stress suggest moderating factors. We examined two established moderators, basal cortisol and parental psychiatric history, simultaneously. We hypothesized that individuals with high basal cortisol, assumed to indicate high context sensitivity, would show relatively high problem levels following chronic stress, especially in the presence of parental psychiatric history. With Linear Mixed Models, we investigated the hypotheses in 1917 Dutch adolescents (53.2 % boys), assessed at ages 11, 13.5, and 16. Low basal cortisol combined with the absence of a parental psychiatric history increased the risk of externalizing but not internalizing problems following chronic stress. Conversely, low basal cortisol combined with a substantial parental psychiatric history increased the risk of internalizing but not externalizing problems following chronic stress. Thus, parental psychiatric history moderated stress- cortisol interactions in predicting psychopathology, but in a different direction than hypothesized. We conclude that the premise that basal cortisol indicates context sensitivity may be too crude. Context sensitivity may not be a general trait but may depend on the nature of the context (e.g., type or duration of stress exposure) and on the outcome of interest (e.g., internalizing vs. externalizing problems). Although consistent across informants, our findings need replication. Keywords: Chronic psychosocial stress; Long-term difficulties; Parental psychiatric history; Externalizing and internalizing problems; Basal cortisol upon waking; Adolescenc

How long does the protective effect on eccentric exercise-induced muscle damage last ?

The selection of optimal preprocessing is among the main bottlenecks in chemometric data analysis. Preprocessing currently is a burden, since a multitude of different preprocessing methods is available for, e.g., baseline correction, smoothing, and alignment, but it is not clear beforehand which method(s) should be used for which data set. The process of preprocessing selection is often limited to trial-and-error and is therefore considered somewhat subjective. In this paper, we present a novel, simple, and effective approach for preprocessing selection. The defining feature of this approach is a design of experiments. On the basis of the design, model performance of a few well-chosen preprocessing methods, and combinations thereof (called <i>strategies</i>) is evaluated. Interpretation of the main effects and interactions subsequently enables the selection of an optimal preprocessing strategy. The presented approach is applied to eight different spectroscopic data sets, covering both calibration and classification challenges. We show that the approach is able to select a preprocessing strategy which improves model performance by at least 50% compared to the raw data; in most cases, it leads to a strategy very close to the true optimum. Our approach makes preprocessing selection fast, insightful, and objective

Cannabis use in people with severe mental illness: the association with physical and mental health - a cohort study. a pharmacotherapy monitoring and outcome survey study

Objective: In the general population cannabis use is associated with better cardiometabolic outcomes. Patients with severe mental illness frequently use cannabis, but also present increased cardiometabolic risk factors. We explore the association between cannabis use and cardiometabolic risk factors in patients with severe mental illness. Method: A total of 3169 patients with severe mental illness from a Dutch cohort were included in the study. The association of cannabis use with body mass index, waist circumference, blood pressure, cholesterol, triglycerides, glucose, glycated hemoglobin and Positive and Negative Syndrome Scale was examined with separate univariate AN(C)OVA. Changes in metabolic risk factors and Positive and Negative Syndrome Scale were examined after a follow-up interval of 9-24 months, for patients who continued, discontinued, started or were never using cannabis between the two assessments. Results: Cannabis users at baseline had lower body mass index, smaller waist circumference, lower diastolic blood pressure, and more severe psychotic symptoms than non-users. Patients who discontinued their cannabis use after the first assessment had a greater increase in body mass index, waist circumference, diastolic blood pressure and triglyceride concentrations than other patients, and the severity of their psychotic symptoms had decreased more compared to continued users and non-users. Conclusion: Extra attention should be paid to the monitoring and treatment of metabolic parameters in patients who discontinue their cannabis use

Persistent low rates of treatment of metabolic risk factors in people with psychotic disorders: a PHAMOUS study

Objective: People with psychotic disorders have an increased metabolic risk and a shortened life expectancy compared to the general population. Two large studies showed that metabolic disorders were untreated in a majority of the patients. Since then, guidelines have urged monitoring of metabolic health. This study examined the course of metabolic disorders over time in people with psychotic disorders and investigated current treatment rates. Methods: A total of 1, 259 patients with psychotic disorders, as defined by the DSM-IV, from 4 Dutch mental health institutions participated in 3 yearly assessments of the Pharmacotherapy Monitoring and Outcome Survey (PHAMOUS) between 2006 and 2014. Patients' metabolic parameters were measured, and the use of pharmacologic treatment for hypertension (systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg), dyslipidemia (5% ≤ Systematic COronary Risk Evaluation [SCORE] risk 7% and/or fasting glucose concentration ≥ 7.2 mmol/L) was recorded. Results: Prevalence of the metabolic syndrome, as defined by the National Cholesterol Education Program criteria, was > 50% at each assessment. On the basis of the European Society of Cardiology guidelines, pharmacotherapy for metabolic disorders was recommended for 52%-59% of the patients at each assessment. Treatment rates with antihypertensive (from 31% to 38%, P <.001) pharmacotherapy increased throughout the assessments. However, half of the patients were not treated for their metabolic risk factors while being monitored for 3 years or longer. Older patients were more likely to receive treatment, and patients who received treatment had lower blood pressure and lower cholesterol and triglyceride concentrations than patients not receiving the recommended treatment. Conclusions: Metabolic risk factors are still seriously undertreated in people with psychotic disorders. Better adherence to and better implementation of guidelines about monitoring and treating metabolic disorders in psychiatry are crucial

Boosting model performance and interpretation by entangling preprocessing selection and variable selection

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Vegetable oils as carbon and energy source for Aureobasidium melanogenum in batch cultivation

Dark homogenous fungal‐based layers called biofinishes and vegetable oils are key ingredients of an innovative wood protecting system. The aim of this study was to determine which of the vegetable oils that have been used to generate biofinishes on wood will provide carbon and energy for the biofinish‐inhabiting fungus Aureobasidium melanogenum, and to determine the effect of the oil type and the amount of oil on the cell yield. Aureobasidium melanogenum was cultivated in shake flasks with different types and amounts of carbon‐based nutrients. Oil‐related total cell and colony‐forming unit growth were demonstrated in suspensions with initially 1% raw linseed, stand linseed, and olive oil. Oil‐related cell growth was also demonstrated with raw linseed oil, using an initial amount of 0.02% and an oil addition during cultivation. Nile red staining showed the accumulation of fatty acids inside cells grown in the presence of oil. In conclusion, each tested vegetable oil was used as carbon and energy source by A. melanogenum. The results indicated that stand linseed oil provides less carbon and energy than olive and raw linseed oil. This research is a fundamental step in unraveling the effects of vegetable oils on biofinish formation