Optimal designs for multivariable spline models

In this paper, we investigate optimal designs for multivariate additive spline regressionmodels. We assume that the knot locations are unknown, so must be estimated from thedata. In this situation, the Fisher information for the full parameter vector depends on theunknown knot locations, resulting in a non-linear design problem. We show that locally,Bayesian and maximin D-optimal designs can be found as the products of the optimaldesigns in one dimension. A similar result is proven for Q-optimality in the class of allproduct design

Notes on the Portrait of Nikias of Cos

In den ausgehenden 40er und 30er Jahren v. Chr. beherrschte der Tyrann Nikias von Kos seine Heimatinsel. Während seiner Herrschaft, deren Dauer sich nicht exakt rekonstruieren lässt, prägte er Münzen mit seinem Porträt. Im vorliegenden Beitrag wird argumentiert, dass die Bildnisse, die entgegen gängiger Forschungsmeinungen weder das Diadem der hellenistischen Könige noch einen Lorbeerkranz tragen, sich aus politischen Gründen an denen Marc Antons orientierten.In the late 40s and 30s BC the tyrant Nikias of Cos reigned his homeland. During his reign, which cannot be dated with absolute certainty, he minted coins with his portrait. This paper argues that these portraits, neither adorned with a royal diadem nor with a laurel wreath contrary to former research, were modelled after those of Marc Antony

The laurel wreath with tainia: Origin and genesis of an imperial insignia

Von einem statistischen Standpunkt betrachtet ist die von Octavian/Augustus am häufigsten getragene Kranzform der Lorbeerkranz mit Tänie. Diese spezifische Kombination zweier Insignien wurde von der archäologischen und numismatischen Forschung nicht beachtet. Der Beitrag erörtert auf Grundlage der Münzprägung des Kaisers die Herkunft dieses kaiserlichen Kopfschmucks und hinterfragt seine Bedeutung.Viewed from a statistical point, the main form of wreath worn by Octavian/Augustus is the laurel wreath with tainia. This specific combination of two insignia has hitherto been disregarded by archaeological and numismatic research. The article traces, based on the coinage of the emperor, the origin of this imperial headgear and questions its meaning

Health-Related Quality of Life Outcomes With Tofacitinib Treatment in Patients With Ulcerative Colitis in the Open-Label Extension Study, OCTAVE Open

BACKGROUND Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We report health-related quality of life (HRQoL) outcomes in patients with ulcerative colitis in the phase 3 open-label, long-term extension study, OCTAVE Open. METHODS The Inflammatory Bowel Disease Questionnaire (IBDQ), EuroQoL-5 Dimensions Health Questionnaire, and 36-Item Short Form Survey scores were analyzed up to month (M) 72 in 4 subpopulations: patients in remission at baseline (maintenance remitters) assigned tofacitinib 5 mg twice daily and patients not in remission at baseline (maintenance nonremitters, maintenance treatment failures, and induction nonresponders [IndNRs]) assigned tofacitinib 10 mg twice daily in OCTAVE Open. Data were analyzed overall and stratified by corticosteroid use at baseline, prior tumor necrosis factor inhibitor failure, and prior immunosuppressant failure. RESULTS Among maintenance remitters and nonremitters, HRQoL outcomes were maintained up to M72: 80.0% and 100.0% of patients had an IBDQ total score ≥170, respectively. At baseline, 7.4% of maintenance treatment failures had an IBDQ total score ≥170, and this increased to 54.3% and 75.0% at M2 and M72, respectively. Corresponding values for IndNRs were 22.6%, 51.0%, and 86.0%. HRQoL outcomes were independent of treatment history. Among patients not in remission at baseline, improvement in EuroQoL-5 Dimensions Health Questionnaire and 36-Item Short Form Survey scores was maintained or achieved by M2, and steady to M72 or M33, with maintenance treatment failures and IndNR subpopulations undergoing the biggest improvements from baseline. CONCLUSIONS A continued favorable impact on HRQoL was revealed with long-term tofacitinib treatment in OCTAVE Open, regardless of baseline remission status or treatment history. (ClinicalTrials.gov; number: NCT01470612)

Decoupled Associative and Dissociative Processes in Strong yet Highly Dynamic Host-Guest Complexes.

Kinetics and thermodynamics in supramolecular systems are intimately linked, yet both are independently important for application in sensing assays and stimuli-responsive switching/self-healing of materials. Host-guest interactions are of particular interest in many water-based materials, sensing, and drug delivery applications. Herein we investigate the binding dynamics of a variety of electron-rich aromatic moieties forming hetero-ternary complexes with the macrocycle cucurbit[8]uril (CB[8]) and an auxiliary guest, dimethyl viologen, with high selectivity and equilibrium binding constants (Keq up to 1014 M-2). Using stopped-flow spectrofluorimetry, association rate constants were observed to approach the diffusion limit and were found to be insensitive to the structure of the guest. Conversely, the dissociation rate constants of the ternary complexes varied dramatically with the guest structure and were correlated with the thermodynamic binding selectivity. Hence differing molecular features were found to contribute to the associative and dissociative processes, mimicking naturally occurring reactions and giving rise to a decoupling of these kinetic parameters. Moreover, we demonstrate the ability to exploit these phenomena and selectively perturb the associative process with external stimuli (e.g., viscosity and pressure). Significantly, these complexes exhibit increased binding equilibria with increasing pressure, with important implications for the application of the CB[8] ternary complex for the formation of hydrogels, as these gels exhibit unprecedented pressure-insensitive rheological properties. A high degree of flexibility therefore exists in the design of host-guest systems with tunable kinetic and thermodynamic parameters for tailor-made applications across a broad range of fields