Therapeutic Reference Range for Aripiprazole in Schizophrenia Revised: a Systematic Review and Metaanalysis

Rationale: While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood levels is questioned by many clinicians. This is due to the often-missing validation of therapeutic reference ranges. Objectives: Here, we present a prototypical meta-analysis of the relationships between blood levels of aripiprazole, its target engagement in the human brain, and clinical effects and side effects in patients with schizophrenia and related disorders. Methods: The relevant literature was systematically searched and reviewed for aripiprazole oral and injectable formulations. Population-based concentration ranges were computed (N = 3,373) and pharmacokinetic influences investigated. Results: Fifty-three study cohorts met the eligibility criteria. Twenty-nine studies report blood level after oral, 15 after injectable formulations, and nine were positron emission tomography studies. Conflicting evidence for a relationship between concentration, efficacy, and side effects exists (assigned level of evidence low, C; and absent, D). Population-based reference ranges are well in-line with findings from neuroimaging data and individual efficacy studies. We suggest a therapeutic reference range of 120-270 ng/ml and 180-380 ng/ml, respectively, for aripiprazole and its active moiety for the treatment of schizophrenia and related disorders. Conclusions: High interindividual variability and the influence of CYP2D6 genotypes gives a special indication for Therapeutic Drug Monitoring of oral and long-acting aripiprazole. A starting dose of 10 mg will in most patients result in effective concentrations in blood and brain. 5 mg will be sufficient for known poor metabolizers

Wissenschaft und Innovation – Wissenschaftsforschung Jahrbuch 1999

Wissenschaft und Innovation wirken in immer stärkerem Maße als Schlüsselfaktoren auf die gesellschaftliche und insbesondere auf die wirtschaftliche Entwicklung ein. Die Wissenschaftsforschung als multidisziplinäres Forschungsvorhaben stellt dafür theoretische Konzepte und handhabbare Instrumentarien bereit. Der Erfolg dieser Bemühungen hängt dabei weitgehend von der Dialogfähigkeit der unterschiedlichen Partner in Wissenschaft, Forschung und Wirtschaft ab. Die vorliegende Publikation setzt die Reihe der Jahrbücher der Gesellschaft für Wissenschaftsforschung fort. Das Jahrbuch 1999 enthält die Konferenzbeiträge zur Tagung „Wissenschaft und Innovation“, die am 26. und 27. März 1999 in Berlin stattfand. In den acht Beiträgen spiegelt sich das breit gefächerte Spektrum der Wissenschaftsforschung anschaulich wider. Neben wissenschaftstheoretischen und bibliometrischen Fragestellungen werden ökonomische und statistische Untersuchungen vorgestellt, die sich auf die gegenwärtige Situation in der deutschen Wirtschaft beziehen.Peer Reviewe

Systematic review and meta-analysis on the therapeutic reference range for escitalopram: Blood concentrations, clinical effects and serotonin transporter occupancy

IntroductionA titration within a certain therapeutic reference range presupposes a relationship between the blood concentration and the therapeutic effect of a drug. However, this has not been systematically investigated for escitalopram. Furthermore, the recommended reference range disagrees with mean steady state concentrations (11–21 ng/ml) that are expected under the approved dose range (10–20 mg/day). This work systematically investigated the relationships between escitalopram dose, blood levels, clinical effects, and serotonin transporter occupancy.MethodsFollowing our previously published methodology, relevant articles were systematically searched and reviewed for escitalopram.ResultsOf 1,032 articles screened, a total of 30 studies met the eligibility criteria. The included studies investigated escitalopram blood levels in relationship to clinical effects (9 studies) or moderating factors on escitalopram metabolism (12 studies) or serotonin transporter occupancy (9 studies). Overall, the evidence for an escitalopram concentration/effect relationship is low (level C).ConclusionBased on our findings, we propose a target range of 20–40 ng/ml for antidepressant efficacy of escitalopram. In maintenance treatment, therapeutic response is expected, when titrating patients above the lower limit. The lower concentration threshold is strongly supported by findings from neuroimaging studies. The upper limit for escitalopram’s reference range rather reflects a therapeutic maximum than a tolerability threshold, since the incidence of side effects in general is low. Concentrations above 40 ng/ml should not necessarily result in dose reductions in case of good clinical efficacy and tolerability. Dose-related escitalopram concentrations in different trials were more than twice the expected concentrations from guideline reports.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=215873], identifier [CRD42020215873]

Tiled Projection onto Bent Screens Using Multi-Projectors

We provide a quick and efficient method to project a coherent image that is seamless and perspectively corrected from one particular viewpoint using an arbitrary number of projectors. The rationale is that wide-angle high-resolution cameras have become much more affordable than short-throw projectors, and only one such camera is sufficient for calibration. Our method is suitable for ad-hoc installations since no 3D reconstruction is required. We provide our method as open source solution, including a demonstrative client program for the Processing framework

Tiled Projection onto Bent Screens Using Multi-Projectors

We provide a quick and efficient method to project a coherent image that is seamless and perspectively corrected from one particular viewpoint using an arbitrary number of projectors. The rationale is that wide-angle high-resolution cameras have become much more affordable than short-throw projectors, and only one such camera is sufficient for calibration. Our method is suitable for ad-hoc installations since no 3D reconstruction is required. We provide our method as open source solution, including a demonstrative client program for the Processing framework

Virtual reality as a teaching method for resuscitation training in undergraduate first year medical students: a randomized controlled trial

Background!#!Virtual reality is an innovative technology for medical education associated with high empirical realism. Therefore, this study compares a conventional cardiopulmonary resuscitation (CPR) training with a Virtual Reality (VR) training aiming to demonstrate: (a) non-inferiority of the VR intervention in respect of no flow time and (b) superiority in respect of subjective learning gain.!##!Methods!#!In this controlled randomized study first year, undergraduate students were allocated in the intervention group and the control group. Fifty-six participants were randomized to the intervention group and 104 participants to the control group. The intervention group received an individual 35-min VR Basic Life Support (BLS) course and a basic skill training. The control group took part in a 'classic' BLS-course with a seminar and a basic skill training. The groups were compared in respect of no flow time in a final 3-min BLS examination (primary outcome) and their learning gain (secondary outcome) assessed with a comparative self-assessment (CSA) using a questionnaire at the beginning and the end of the course. Data analysis was performed with a general linear fixed effects model.!##!Results!#!The no flow time was significantly shorter in the control group (Mean values: control group 82 s vs. intervention group 93 s; p = 0.000). In the CSA participants of the intervention group had a higher learning gain in 6 out of 11 items of the questionnaire (p < 0.05).!##!Conclusion!#!A 'classic' BLS-course with a seminar and training seems superior to VR in teaching technical skills. However, overall learning gain was higher with VR. Future BLS course-formats should consider the integration of VR technique into the classic CPR training or vice versa, to use the advantage of both teaching techniques

Ring's Anatomy - Parametric Design of Wedding Rings

We present a use case that demonstrates the effectiveness of procedural shape modeling for mass customization of consumer products. We show a metadesign that is composed of a few well-defined procedural shape building blocks. It can generate a large variety of shapes and covers most of a design space defined by a collection of exemplars, in our case wedding rings. We describe the process of model abstraction for the shape space spanned by these shapes, arguing that the same is possible for other shape design spaces as well

Tiled Projection Onto Deforming Screens

For the next generation of visual installations it will not be sufficient to surround the visitor by stunning responsive audiovisual experiences - the next step is that space itself deforms in response to the user or user groups. Dynamic reconfigurable spaces are a new exciting possibility to influence the behaviour of groups and individuals; they may have the potential of stimulating various different social interactions and behaviours in a user-adapted fashion. However, some technical hurdles must be overcome. Projecting on larger surfaces, like a ceiling screen of 6 x 8 meters, is typically possible only with a tiled projection, i.e., with multiple projectors creating one large seamless image. This works well with a static ceiling; however, when the ceiling dynamically moves and deforms, the tiling becomes visible since the images no longer match. In this paper we present a method that can avoid such artifacts by dynamically adjusting the tiled projection to the deforming surface. Our method is surprisingly simple and efficient, and it does not require any image processing at runtime, nor any 3D reconstruction of the surface at any point