Statistical inference for ordinal predictors in generalized additive models with application to Bronchopulmonary Dysplasia.

Objective: Discrete but ordered covariates are quite common in applied statistics, and some regularized fitting procedures have been proposed for proper handling of ordinal predictors in statistical models. Motivated by a study from neonatal medicine on Bronchopulmonary Dysplasia (BPD), we show how quadratic penalties on adjacent dummy coefficients of ordinal factors proposed in the literature can be incorporated in the framework of generalized additive models, making tools for statistical inference developed there available for ordinal predictors as well.

Results: The approach presented allows to exploit the scale level of ordinally scaled factors in a sound statistical framework.

Protein intake and outcome of critically ill patients: analysis of a large international database using piece-wise exponential additive mixed models.

Background: Proteins are an essential part of medical nutrition therapy in critically ill patients. Guidelines almost universally recommend a high protein intake without robust evidence supporting its use.

Methods: Using a large international database, we modelled associations between the hazard rate of in-hospital death and live hospital discharge (competing risks) and three categories of protein intake (low: < 0.

Reported and Recorded Sleepiness in Obesity and Depression.

Background: Obesity and depression are both associated with changes in sleep/wake regulation, with potential implications for individualized treatment especially in comorbid individuals suffering from both. However, the associations between obesity, depression, and subjective, questionnaire-based and objective, EEG-based measurements of sleepiness used to assess disturbed sleep/wake regulation in clinical practice are not well known.

Objectives: The study investigates associations between sleep/wake regulation measures based on self-reported subjective questionnaires and EEG-derived measurements of sleep/wake regulation patterns with depression and obesity and how/whether depression and/or obesity affect associations between such self-reported subjective questionnaires and EEG-derived measurements.

Why some obese people become depressed whilst others do not: exploring links between cognitive reactivity, depression and obesity.

Obesity and depression are two major public health concerns, particularly when they co-occur. To date, mechanisms underlying this association have not been established and it is unclear why some obese people become depressed whilst others do not. However, considering the strong association between depression and cognitive reactivity (CR), the present study explores possible associations between obesity, depression and CR in light of the scarce and conflicting nature of past literature.

Penalized estimation of complex, non-linear exposure-lag-response associations.

We propose a novel approach for the flexible modeling of complex exposure-lag-response associations in time-to-event data, where multiple past exposures within a defined time window are cumulatively associated with the hazard. Our method allows for the estimation of a wide variety of effects, including potentially smooth and smoothly time-varying effects as well as cumulative effects with leads and lags, taking advantage of the inference methods that have recently been developed for generalized additive mixed models. We apply our method to data from a large observational study of intensive care patients in order to analyze the association of both the timing and the amount of artificial nutrition with the short term survival of critically ill patients.

An experimental test of the habitat-amount hypothesis for saproxylic beetles in a forested region.

The habitat-amount hypothesis challenges traditional concepts that explain species richness within habitats, such as the habitat-patch hypothesis, where species number is a function of patch size and patch isolation. It posits that effects of patch size and patch isolation are driven by effects of sample area, and thus that the number of species at a site is basically a function of the total habitat amount surrounding this site. We tested the habitat-amount hypothesis for saproxylic beetles and their habitat of dead wood by using an experiment comprising 190 plots with manipulated patch sizes situated in a forested region with a high variation in habitat amount (i.

A penalized framework for distributed lag non-linear models.

Distributed lag non-linear models (DLNMs) are a modelling tool for describing potentially non-linear and delayed dependencies. Here, we illustrate an extension of the DLNM framework through the use of penalized splines within generalized additive models (GAM). This extension offers built-in model selection procedures and the possibility of accommodating assumptions on the shape of the lag structure through specific penalties.

Thrombus Histology Suggests Cardioembolic Cause in Cryptogenic Stroke.

Background And Purpose: Ischemic stroke of undetermined cause is a major health issue because of its high frequency and clinical relevance. Histopathologic analysis of human thrombi, retrieved from stroke patients with large-vessel occlusion during mechanical thrombectomy, may provide information about underlying pathologies. This study examines the relationship between stroke causes and histological clot composition to identify specific patterns that might help to distinguish causes of cryptogenic stroke.

Functional Additive Mixed Models.

We propose an extensive framework for additive regression models for correlated functional responses, allowing for multiple partially nested or crossed functional random effects with flexible correlation structures for, e.g., spatial, temporal, or longitudinal functional data.

Functional Generalized Additive Models.

We introduce the functional generalized additive model (FGAM), a novel regression model for association studies between a scalar response and a functional predictor. We model the link-transformed mean response as the integral with respect to of {(), } where (·,·) is an unknown regression function and () is a functional covariate. Rather than having an additive model in a finite number of principal components as in Müller and Yao (2008), our model incorporates the functional predictor directly and thus our model can be viewed as the natural functional extension of generalized additive models.

Clinical effectiveness of hymenoptera venom immunotherapy: a prospective observational multicenter study of the European academy of allergology and clinical immunology interest group on insect venom hypersensitivity.

Background: Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors.

Objective: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase.

Methods: In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached.

Quantification of leukocyte genomic 5-methylcytosine levels reveals epigenetic plasticity in healthy adult cloned cattle.

Successful somatic cell nuclear transfer (SCNT) requires epigenetic reprogramming of a differentiated donor cell nucleus. Incorrect reprogramming of epigenetic markings such as DNA methylation is associated with compromised prenatal development and postnatal abnormalities. Clones that survive into adulthood, in contrast, are assumed to possess a normalized epigenome corresponding to their normal phenotype.

Predictors of side effects during the buildup phase of venom immunotherapy for Hymenoptera venom allergy: the importance of baseline serum tryptase.

Background: Severe side effects during venom immunotherapy (VIT) are associated with a variety of risk factors.

Objective: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters, which are routinely recorded during patient evaluation, with the frequency of severe reactions requiring an emergency intervention during the buildup phase of VIT.

Methods: In this observational prospective multicenter study, we enrolled 680 patients with established honeybee or vespid venom allergy who underwent VIT.

Predictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: importance of baseline serum tryptase-a study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity.

Background: Severe anaphylaxis to honeybee or vespid stings is associated with a variety of risk factors, which are poorly defined.

Objective: Our aim was to evaluate the association of baseline serum tryptase concentrations and other variables routinely recorded during patient evaluation with the frequency of past severe anaphylaxis after a field sting.

Methods: In this observational multicenter study, we enrolled 962 patients with established bee or vespid venom allergy who had a systemic reaction after a field sting.

Fear-related behaviour of dogs in veterinary practice.

To investigate further the occurrence of fear-related behaviour in dogs in veterinary practice and to evaluate associated factors, 135 dogs were observed under practice conditions within the framework of a standardised test examination and the owners interviewed using a questionnaire. Most dogs exhibited fear reactions, particularly on the examination table, with 78.5% (106/135) categorised as 'fearful' based on their behaviour.