Group-by-Treatment Interaction Effects in Comparative Bioavailability Studies.

Comparative bioavailability studies often involve multiple groups of subjects for a variety of reasons, such as clinical capacity limitations. This raises questions about the validity of pooling data from these groups in the statistical analysis and whether a group-by-treatment interaction should be evaluated. We investigated the presence or absence of group-by-treatment interactions through both simulation techniques and a meta-study of well-controlled trials.

Pharmacokinetics of a Modified-Release Dexamphetamine Sulfate Formulation Following Single and Multiple Dosing in Healthy Adults: Comparative Bioavailability with Immediate-Release Dexamphetamine Sulfate, between Strengths, Assessment of Food and Meal Composition Effects.

Background: A modified-release dexamphetamine sulfate formulation (DEX-MR) is under development for the treatment of attention-deficit/hyperactivity disorder.

Objective: We investigated the bioequivalence of once-daily DEX-MR to twice-daily immediate-release dexamphetamine sulfate (DEX-IR) after single and multiple dosing and between strengths, and effects of food and meal types.

Method: Three randomized, open-label, crossover studies in healthy males were conducted.

Diagnostic accuracy of endoscopic ultrasonography-guided tissue acquisition prior to resection of pancreatic carcinoma: a nationwide analysis.

Introduction: Endoscopic ultrasonography guided tissue acquisition (EUS + TA) is used to provide a tissue diagnosis in patients with suspected pancreatic cancer. Key performance indicators (KPI) for these procedures are rate of adequate sample (RAS) and sensitivity for malignancy (SFM).

Aim: assess practice variation regarding KPI of EUS + TA prior to resection of pancreatic carcinoma in the Netherlands.

Sexually mediated phenotypic variation within and between sexes as a continuum structured by ecology: The mosaic nature of skeletal variation across body regions in Threespine stickleback ( L.).

Ecological character displacement between the sexes, and sexual selection, integrate into a convergent set of factors that produce sexual variation. Ecologically modulated, sexually mediated variation within and between sexes may be a major contributor to the amount of total variation that selection can act on in species. Threespine stickleback () display rapid adaptive responses and sexual variation in many phenotypic traits.

Critical Remarks on Reference-Scaled Average Bioequivalence.

Purpose: More than a decade ago the option to assess highly variable drugs / drug products by reference-scaled average bioequivalence was introduced in regulatory practice. Recommended approaches differ between jurisdictions and may lead to different conclusions even for the same data set. According to our knowledge, implemented methods have not been directly compared for their operating characteristics (Type I Error and power).

Implications of Anion Structure on Physicochemical Properties of DBU-Based Protic Ionic Liquids.

Protic ionic liquids (PILs) are potential candidates as electrolyte components in energy storage devices. When replacing flammable and volatile organic solvents, PILs are expected to improve the safety and performance of electrochemical devices. Considering their technical application, a challenging task is the understanding of the key factors governing their intermolecular interactions and physicochemical properties.

Cumulative sum learning curves guiding multicenter multidisciplinary quality improvement of EUS-guided tissue acquisition of solid pancreatic lesions.

 In this study, we evaluated the performance of community hospitals involved in the Dutch quality in endosonography team regarding yield of endoscopic ultrasound (EUS)-guided tissue acquisition (TA) of solid pancreatic lesions using cumulative sum (CUSUM) learning curves. The aims were to assess trends in quality over time and explore potential benefits of CUSUM as a feedback-tool. All consecutive EUS-guided TA procedures for solid pancreatic lesions were registered in five community hospitals between 2015 and  2018.

Enhanced Li Transport in Ionic Liquid-Based Electrolytes Aided by Fluorinated Ethers for Highly Efficient Lithium Metal Batteries with Improved Rate Capability.

FSI -based ionic liquids (ILs) are promising electrolyte candidates for long-life and safe lithium metal batteries (LMBs). However, their practical application is hindered by sluggish Li transport at room temperature. Herein, it is shown that additions of bis(2,2,2-trifluoroethyl) ether (BTFE) to LiFSI-Pyr FSI ILs can effectively mitigate this shortcoming, while maintaining ILs' high compatibility with lithium metal.

Do endosonographers agree on the presence of bile duct sludge and the subsequent need for intervention?

 Endoscopic ultrasonography (EUS) is a tool widely used to diagnose bile duct lithiasis. In approximately one out of five patients with positive findings at EUS, sludge is detected in the bile duct instead of stones. The objective of this study was to establish the agreement among endosonographers regarding: 1.

Acidic Ionic Liquids Enabling Intermediate Temperature Operation Fuel Cells.

Herein we show that protic ionic liquids (PILs) are promising electrolytes for fuel cells operating in the temperature range 100-120 °C. ,-Diethyl--methyl-3-sulfopropan-1-ammonium hydrogen sulfate ([DEMSPA][HSA]), ,-diethyl--methyl-3-sulfopropan-1-ammonium triflate ([DEMSPA][TfO]), ,-diethyl-3-sulfopropan-1-ammonium hydrogen sulfate ([DESPA][HSA]), and ,-diethyl-3-sulfopropan-1-ammonium triflate ([DESPA][TfO]) are investigated in this study with regard to their specific conductivity, thermal stability, viscosity, and electrochemical properties. The [DEMSPA][TfO] and [DESPA][TfO] electrolytes offer high limiting current densities for the oxygen reduction reaction (ORR) on platinum electrodes, that is, about 1 order of magnitude larger than 98% HPO.

From panic to pedagogy: Using online active learning to promote inclusive instruction in ecology and evolutionary biology courses and beyond.

The rapid shift to online teaching in spring 2020 meant most of us were teaching in panic mode. As we move forward with course planning for fall and beyond, we can invest more time and energy into improving the online experience for our students. We advocate that instructors use inclusive teaching practices, specifically through active learning, in their online classes.

Assessing goodness-of-fit for evaluation of dose-proportionality.

For the clinical development of a new drug, the determination of dose-proportionality is an essential part of the pharmacokinetic evaluations, which may provide early indications of non-linear pharmacokinetics and may help to identify sub-populations with divergent clearances. Prior to making any conclusions regarding dose-proportionality, the goodness-of-fit of the model must be assessed to evaluate the model performance. We propose the use of simulation-based visual predictive checks to improve the validity of dose-proportionality conclusions for complex designs.

System design of a physiological ambient illumination adaptation for subretinal stimulator.

Subretinal stimulators help restoring vision to blind people, suffering from degenerative eye diseases. This work aims to reduce patient's efforts to continuously tune his device, by implementing a physiological ambient illumination adaptation system. The parameters of the adaptation to changing illumination conditions are highly customizable, to best fit individual patients requirements.

An iterative method to protect the type I error rate in bioequivalence studies under two-stage adaptive 2×2 crossover designs.

Bioequivalence studies are the pivotal clinical trials submitted to regulatory agencies to support the marketing applications of generic drug products. Average bioequivalence (ABE) is used to determine whether the mean values for the pharmacokinetic measures determined after administration of the test and reference products are comparable. Two-stage 2×2 crossover adaptive designs (TSDs) are becoming increasingly popular because they allow making assumptions on the clinically meaningful treatment effect and a reliable guess for the unknown within-subject variability.

Prevalence and psychosocial correlates of subjectively perceived decline in five cognitive domains: Results from a population-based cohort study in Germany.

Objective: Subjective cognitive decline (SCD) was frequently investigated for memory in healthy aging or in relation to diseases like dementia. It was found to be related to sociodemographic and psychological variables as well as cognitive abilities. The prevalence of SCD in other cognitive domains and their relation to these variables is largely unknown to date.

Reference Datasets for Studies in a Replicate Design Intended for Average Bioequivalence with Expanding Limits.

In order to help companies qualify and validate the software used to evaluate bioequivalence trials in a replicate design intended for average bioequivalence with expanding limits, this work aims to define datasets with known results. This paper releases 30 reference datasets into the public domain along with proposed consensus results. A proposal is made for results that should be used as validation targets.

Brief Sensory Training Narrows the Temporal Binding Window and Enhances Long-Term Multimodal Speech Perception.

Our ability to integrate multiple sensory-based representations of our surrounding supplies us with a more holistic view of our world. There are many complex algorithms our nervous system uses to construct a coherent perception. An indicator to solve this 'binding problem' are the temporal characteristics with the specificity that environmental information has different propagation speeds (e.

Circulating levels of PD-L1 and Galectin-9 are associated with patient survival in surgically treated Hepatocellular Carcinoma independent of their intra-tumoral expression levels.

Tumor expression of immune co-inhibitory ligands, such as PD-L1 and Galectin-9, have potential prognostic value in Hepatocellular Carcinoma (HCC). Circulating levels of these molecules, however, have hardly been studied. This study aims to assess the prognostic significance of circulating PD-L1 and circulating Galectin-9 in patients with resected HCC, and to compare their prognostic significance to the intra-tumoral expression of these same molecules.

Sample size determination in bioequivalence studies using statistical assurance.

Aims: Bioequivalence (BE) trials aim to demonstrate that the 90% confidence interval of the T/R-ratio of the pharmacokinetic metrics between two formulations (test [T] and reference [R]) of a drug is fully included in the acceptance interval [0.80, 1.25].

Pharmacokinetic modelling and validation of the half-life extension needed to reduce the burden of infusions compared with standard factor VIII.

Introduction: Currently, no universally accepted definition of extended half-life (EHL) recombinant FVIII (rFVIII) exists. Identifying the minimum half-life extension ratio required for a reduction in dosing frequency compared with standard rFVIII could enable a more practical approach to decisions around prophylaxis with EHL rFVIII.

Aim: To identify the half-life extension ratio required to decrease rFVIII dosing frequency by at least 1 day while maintaining the proportion of patients with plasma rFVIII levels above 1 IU/dL and without increasing the total weekly dose.

Mitochondrial haplotypes are not associated with mice selectively bred for high voluntary wheel running.

Mitochondrial haplotypes have been associated with human and rodent phenotypes, including nonshivering thermogenesis capacity, learning capability, and disease risk. Although the mammalian mitochondrial D-loop is highly polymorphic, D-loops in laboratory mice are identical, and variation occurs elsewhere mainly between nucleotides 9820 and 9830. Part of this region codes for the tRNA gene and is associated with mitochondrial densities and number of mtDNA copies.

Locomotor activity, growth hormones, and systemic robusticity: An investigation of cranial vault thickness in mouse lines bred for high endurance running.

Objectives: To use a mouse model to investigate the relationships among the components of the systemic robusticity hypothesis (SRH): voluntary exercise on wheels, spontaneous physical activity (SPA) in cages, growth hormones, and skeletal robusticity, especially cranial vault thickness (CVT).

Materials And Methods: Fifty female mice from lines artificially selected for high running (HR) and 50 from nonselected control (C) lines were housed in cages with (Active) or without wheels (Sedentary). Wheel running and SPA were monitored daily.