Optimal experimental designs for inverse quadratic regression models

In this paper optimal experimental designs for inverse quadratic regression models are determined. We consider two different parameterizations of the model and investigate local optimal designs with respect to the $c$-, $D$- and $E$-criteria, which reflect various aspects of the precision of the maximum likelihood estimator for the parameters in inverse quadratic regression models. In particular it is demonstrated that for a sufficiently large design space geometric allocation rules are optimal with respect to many optimality criteria. Moreover, in numerous cases the designs with respect to the different criteria are supported at the same points. Finally, the efficiencies of different optimal designs with respect to various optimality criteria are studied, and the efficiency of some commonly used designs are investigated.Comment: 24 page

Molekularbiologische, zellbiologische und funktionelle Analyse der L-Glutamat-Neurotransmitter Transporter des Zentralnervensystems

In dieser Arbeit sollte zum, Studium der normalen und pathophysiologischen Bedeutung des GLT-1 Transporters ein Astrozyten-spezifisch und entwicklungsabhängig induzierbares konditionelle glt-1 null Mausmodell erstellt und analysiert werden. Zur Herstellung dieses Mausmodells für die konditionelle Gen-Ausschaltung des Glutamattransporters GLT-1 wurden zwei unterschiedliche replacement Vektoren GLTBS und GLT-RF konstruiert. Mit dem Nachweis der korrekten genomischen DNA Sequenz des gesamten GLT-RF targeting Konstruktes, der Isolierung homolog rekombinierter ES-Zell Klone, Überprüfung der Pluripotenz und des Karyotyps wurden die Rahmenbedingungen für die Generierung einer konditionellen GLT-1 Maus geschaffen. Durch Vorkern-Mikroinjektion wurde bisher eine Cre-Rekombinase exprimierende transgene Mauslinie generiert, die auf der Basis des TetOn Systems unter dem Astrozyten spezifischen Promoter gfap die Cre�Rekombinase Doxycyclin induzierbar exprimiert. Die funktionelle Analyse dieser transgenen Mauslinie zeigte keine Aktivierbarkeit. In glialen Zellkulturstudien hingegen wurde eine präzise Induktion der Cre-Rekombinase erzielt. Auf einem ähnlichen Konstrukt mit der Doxyzyklin induzierbaren Cre-Rekombinase, in dem gfap durch den myelinspezifischen mbp Promoter ersetzt wurde, zeigten im Tiermodell nach oraler Doxyzyclin Applikation eine präzise ausgelöste Induktion. In weiteren Studien zur Bedeutung der beiden anderen hauptsächlichen Glutamat Transporter wurden frühere Beobachtungen an GLAST-1 defizienten und Maus- Doppelmutanten GLAST-1/EAAC1 durch den wichtigen Befund, dass überwiegend weibliche Doppelmutanten im Alter von einem Jahr epileptische Anfälle entwickeln. Analysen zur Beziehung Glutamat Transporter und Glutamat Rezeptor-Expression zeigten dass sechs Wochen alte GLAST-1 -/- und GLAST-1 -/- / EAAC1 -/- Mäuse eine gesteigerte Expression des ionotropen Kainatrezeptors aufweisen. Expressionsmuster der Glutamatrezeptoren und der Glutamattransporter in Abhängigkeit des Neurotransmitters Glutamat wurden ermittelt. Dabei wurde der regulatorischeEinfluss der glutamatergen Transmission auf die mRNA Transkription aufgezeigt

Two hydroxy pyridinecarboxylic acid derivatives as a possible chelating agents in neurodegenerative disease; equilibrium complexation studies with Cu(II), Zn(II).

The metal ion chelators 4-hydroxy-5-methyl-3-pyridinecarboxylic acid (DQ5) and 1,5-dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ715) and Cu(II) and Zn(II) were investigated with the aim to restore the homeostasis of the brain Cu(II) and Zn(II) in neurodegenerative diseases. The proton dissociation constants of the ligands, the stability constants, and the coordination modes of the metal complexes formed were determined by pH-potentiometric, and spectral (UV–Vis and EPR or 1H NMR) methods. The results show that in slightly acidic and neutral pH range mono and bis complexes are formed through bidentate coordination of the ligands. The biological MTT-test reveals that the DQ715 ligand is able to lower the cytotoxic effect of Cu(II) in human embryonic kidney HEK-293 cells. Our studies revealed, however, that none of the chelators were efficient enough to withdraw these metal ions from the amyloid aggregates

Optimal designs for the EMAX, log-linear and exponential model

In this paper we derive locally D- and ED_p-optimal designs for the exponential, log-linear and three parameter EMAX-model. We show that for each model the locally D- and ED_p-optimal designs are supported at the same set of points, while the corresponding weights are different. This indicates that for a given model, D-optimal designs are efficient for estimating the smallest dose which achieves 100p% of the maximum effect in the observed dose range. Conversely, ED_p-optimal designs also yield good D-efficiencies. We illustrate the results using several examples and demonstrate that locally D- and ED_p-optimal designs for the EMAX-, log-linear and exponential model are relatively robust with respect to misspecification of the model parameters

Get Some Skin in the Game: Best Practices for Pediatric Skin Care

Care of patients’ skin is a nurse-sensitive outcome measure established by the American Nurses Association (Young & Clark, 2009). Maintaining skin integrity in the critical-care environment is difficult because of patient acuity and the highly invasive interventions and therapies they receive (Galvin & Curley, 2012). The prevalence, prevention, and treatment of skin breakdown have been studied in adults, but research is lacking for children (Groeneveld et al., 2003). Pediatric patients have different anatomic, physiologic and developmental factors that alter their risk of obtaining and presentation of hospital acquired pressure ulcers (HAPUs), (Noonan, Quigley & Curley, 2013). Medical devices monitoring has become standard of practice for the acute care environment and clinicians have recognized that medical devices placed against the skin or mucosal membranes can lead to pressure ulcer development (Noonan et al., 2013). Medical Device Related (MDR) pressure ulcers are different then pressure ulcers derived on bony prominences because they are produced from unrelieved tissue compression on the site where the medical device is in contact with skin or mucosal membranes (Noonan et al., 2013). Due to the acute nature of the patients in critical care settings, nursing interventions focus on support of vital functions; and skin breakdown is generally not the main concern during admission (Smitt, Woensel, & Bos, 2011). Ensuring that nurses in the critical care area regard preventive skin care as a priority is critical for success in skin-breakdown interventions (Drake, Wendi, Sherburne, Nugent, & Simpson, 2012). Current work is being done by Martha Curley to create a risk prediction tool for MDR HAPUs that will inform and optimize prevention and treatment (Noonan et al, 2013). With this new knowledge, and in the absence of any current national standards it was identified, through a pilot project in a pediatric Cardiac Intensive Care Unit (PCICU) in a large hospital in Upstate New York, that there was a lack of standardization in device related skin care for patients. For the pilot project a practice guideline was created that guided PCICU nurses on the interventions for potential skin-breakdown issues in their patients. The patients had a significant change in skin breakdown with a one-sided Fishers Exact Test (P=.0422). A logistic regression model showed intervention as a significant factor in reducing incidence of pressure ulcers, skin breakdown, and length of stay (P=.0389). The current study is looking at the effects of an educational intervention with nurses, and implementation of the skin care practice guideline across all pediatric care areas. Disseminating the results and tools to replicate the practice guideline is essential for implementing current evidence based best practice across pediatrics, and is timely with the anticipation of the release of risk prediction tool for MDR HAPUs

3D shape of Orion A from Gaia DR2

Reproduced with permission from Astronomy & Astrophysics. © 2018 ESO.We use the Gaia DR2 distances of about 700 mid-infrared selected young stellar objects in the benchmark giant molecular cloud Orion A to infer its 3D shape and orientation. We find that Orion A is not the fairly straight filamentary cloud that we see in (2D) projection, but instead a cometary-like cloud oriented toward the Galactic plane, with two distinct components: a denser and enhanced star-forming (bent) Head, and a lower density and star-formation quieter ~75 pc long Tail. The true extent of Orion A is not the projected ~40 pc but ~90 pc, making it by far the largest molecular cloud in the local neighborhood. Its aspect ratio (~30:1) and high column-density fraction (~45%) make it similar to large-scale Milky Way filaments ("bones"), despite its distance to the galactic mid-plane being an order of magnitude larger than typically found for these structures.Peer reviewedFinal Accepted Versio

Elevated romantic love and jealousy if relationship status is declared on Facebook

Declared relationship status on Facebook can serve as a public commitment and as an extra layer of a couple’s security. However, the question arises: do those who report the relationship status feel stronger romantic love and jealousy towards their partners than those who do not share such information publicly? To test this assumption, profile information and questionnaire data of romantic love and jealousy were gathered from 292 (230 females) respondents that were in a relationship. Our results suggest that announcing the relationship status is associated with elevated romantic love and jealousy. Therefore, being “Facebook official” can be interpreted as a tie-sign indicating that the couple is “out of the market”, and can promote their unity as a “digital wedding ring”