Showing papers by "Michael Wagner published in 2004"
TL;DR: Results from preliminary analysis of data covering a two-year period demonstrate that both the early-recognition inventory plus cognitive tests and the two therapy strategies are feasible and the objective of implementing effective and practical secondary prevention of psychosis and its consequences will be attained.
Abstract: As effective and practical approaches to primary and universal prevention of psychosis are lacking, intervention efforts are targeted at the early stages of schizophrenia to prevent (by way of secondary prevention) or postpone psychosis onset, reduce severity of illness or at least ameliorate the social consequences involved. Early intervention requires early detection and early recognition (diagnosis) of persons at risk and early prediction of psychosis. Within the German Research Network on Schizophrenia (GRNS) awareness programmes are being carried out in several German cities, and these efforts are already improving utilisation of early-recognition and early-prediction services by at risk persons. The empirical basis of developing a two-step early-recognition inventory and strategies of application will be discussed. This instrument is supplemented by a set of cognitive tests, prospectively validated in the GRNS. Results from preliminary analysis of data covering a two-year period demonstrate that the inventory and the cognitive tests are readily accepted. When used for screening in non-specialist settings and at the next level, i. e. at early-recognition centres, they seem to permit identification of at-risk persons. Early intervention is being tested 1) in a randomised controlled multi-centre trial consisting of a specially developed cognitive-behavioural therapy in the early (prepsychotic) prodromal state and 2) on additional treatment with appropriate doses of amisulpride in the late prodromal (early psychotic) state. Preliminary data from Study 1 covering 16.3 months show significantly fewer transitions to psychosis and from Study 2 reduced positive and negative symptoms and improved global functioning compared with controls who had received normal clinical treatment. As a result, both the early-recognition inventory plus cognitive tests and the two therapy strategies are feasible. We hope that the favourable trend indicated by the preliminary data will be confirmed in the final analysis planned for 2005 and the objective of implementing effective and practical secondary prevention of psychosis and its consequences will be attained.
214 citations
TL;DR: Uv picosecond laser diodes have a large potential in high resolution fluorescence microscopy and fluorescence lifetime endoscopy and are indicated by variations of the ratio of free and protein bound NADH.
Abstract: Lifetime images of autofluorescence of cultivated endothelial cells were recorded using a novel picosecond laser diode in the near ultraviolet range (375 nm). In contrast to existing picosecond light sources this wavelength permits efficient excitation of the free and protein bound coenzyme NADH with fluorescence lifetimes of 0.4-0.5 ns and 2.0-2.5 ns, respectively. The effective fluorescence lifetime tau(eff) (depending on both lifetimes) was homogenously distributed over the cells with some shortening in the perinuclear region, possibly close to mitochondria. A slight decrease of tau(eff) was observed after inhibition of the mitochondrial respiratory chain, whereas a slight increase was observed after inhibition of the glycolytic pathway, thus indicating variations of the ratio of free and protein bound NADH. Although present applications are still limited by their low pulse energy (< or = 5 pJ), uv picosecond laser diodes have a large potential in high resolution fluorescence microscopy and fluorescence lifetime endoscopy.
109 citations
TL;DR: The results suggest that the functional consequences of chronic MDMA use may be explained by 5-HT receptor changes rather than by a chronic 5- HT deficiency condition, and that use of cannabis does not lead to alterations of amplitude, habituation, or PPI of ASR.
107 citations
TL;DR: Elevated neuroticism, depressive temperament and dysfunctional regulation of the hypothalamic–pituitary–adrenocortical (HPA) system are considered as risk factors for unipolar depression.
Abstract: Objective: Elevated neuroticism, depressive temperament and dysfunctional regulation of the hypothalamic–pituitary–adrenocortical (HPA) system are considered as risk factors for unipolar depression. An interaction of these vulnerability factors was suggested, but controversially discussed. In absence of other informative studies we set out for a replication test and for elucidation of the underlying mechanism.
Method: Ninety-two subjects recruited in the community-performed assessments of personality and temperament as well as measurement of HPA function with the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test.
Results: Cortisol levels subsequent to Dex/CRH challenge were associated with neuroticism; high-neuroticism subjects revealed a higher HPA activation. This difference was mainly because of male subjects ≥25 years. A similar relationship was observed for depressive temperament.
Conclusion: This constellation may propose that HPA dysregulation is the endocrinological basis for neuroticism and depressive temperament; this result supports the view that distinct personality factors and HPA vulnerability interact in mediating depression.
100 citations
TL;DR: The overall goal is to implicate peaks that have a high likelihood of being biologically linked to a given disease state, and thus to narrow the search for biomarker candidates.
Abstract: Recent technological advances in mass spectrometry pose challenges in computational mathematics and statistics to process the mass spectral data into predictive models with clinical and biological significance. We discuss several classification-based approaches to finding protein biomarker candidates using protein profiles obtained via mass spectrometry, and we assess their statistical significance. Our overall goal is to implicate peaks that have a high likelihood of being biologically linked to a given disease state, and thus to narrow the search for biomarker candidates. Thorough cross-validation studies and randomization tests are performed on a prostate cancer dataset with over 300 patients, obtained at the Eastern Virginia Medical School using SELDI-TOF mass spectrometry. We obtain average classification accuracies of 87% on a four-group classification problem using a two-stage linear SVM-based procedure and just 13 peaks, with other methods performing comparably. Modern feature selection and classification methods are powerful techniques for both the identification of biomarker candidates and the related problem of building predictive models from protein mass spectrometric profiles. Cross-validation and randomization are essential tools that must be performed carefully in order not to bias the results unfairly. However, only a biological validation and identification of the underlying proteins will ultimately confirm the actual value and power of any computational predictions.
95 citations
TL;DR: It is suggested that improvement of working memory is more sensitive to the changes of hormones of the HPA system (e.g. cortisol) than other cognitive functions and the global severity of depression.
76 citations
TL;DR: The new method adds a new and important dimension to dipole source reconstruction results by characterizing their reliability and deciding how many dipoles are necessary to explain the measured data, since superfluous dipoles exhibit rather large confidence volumes.
62 citations
05 Dec 2004
TL;DR: A simulation framework for the evaluation and optimization of scheduling rules is presented and an experience with a preliminary implementation for the Division of Pediatric Ophthalmology at Cincinnati Children's Hospital Medical Center is summarized.
Abstract: The process by which outpatients are scheduled for a doctor's visit is a crucial determinant of the overall efficiency of the patient flow. The problem at hand consists of determining prioritization (triage) rules so that adequate patient care is guaranteed, resources (provider schedules) are utilized efficiently and a service guarantee can be ensured. We present a simulation framework for the evaluation and optimization of scheduling rules. We outline the basic ingredients of our model, illustrate the kinds of analyses it has enabled us to perform and summarize our experience with a preliminary implementation for the Division of Pediatric Ophthalmology at Cincinnati Children's Hospital Medical Center. Challenges for adaptations to other settings are also outlined.
55 citations
48 citations
TL;DR: Non-radiative energy transfer was used to detect laurdan selectively in close proximity to a molecular acceptor (DiI) and may present a possibility for measuring membrane dynamics in specific microenvironments.
Abstract: Membranes of living cells are characterized by laser-assisted fluorescence microscopy, in particular a combination of microspectrofluorometry, total internal reflection fluorescence microscopy (TIRFM), fluorescence lifetime imaging (FLIM) and Forster resonance energy transfer (FRET) spectroscopy. The generalized polarization (GP, characterizing a spectral shift which depends on the phase of membrane lipids) as well as the effective fluorescence lifetime (τeff) of the membrane marker laurdan were revealed to be appropriate parameters for membrane stiffness and fluidity. GP decreased with temperature, but increased during cell growth and was always higher for the plasma membrane than for intracellular membranes. Microdomains of different fluorescence lifetimes τeff were observed at temperatures above 30 °C and disappeared during cell aging. Non-radiative energy transfer was used to detect laurdan selectively in close proximity to a molecular acceptor (DiI) and may present a possibility for measuring membrane dynamics in specific microenvironments.
46 citations
TL;DR: Large-scale optimization techniques to model the energy function that underlies the folding process of proteins are presented by tailoring and parallelizing the interior-point code PCx.
Abstract: We present large-scale optimization techniques to model the energy function that underlies the folding process of proteins. Linear Programming is used to identify parameters in the energy function model, the objective being that the model predict the structure of known proteins correctly. Such trained functions can then be used either for ab-initio prediction or for recognition of unknown structures. In order to obtain good energy models we need to be able to solve dense Linear Programming Problems with tens (possibly hundreds) of millions of constraints in a few hundred parameters, which we achieve by tailoring and parallelizing the interior-point code PCx.
Patent•
05 May 2004
TL;DR: In this article, the authors describe reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa) in the formulae (I) and (II), in which RO, R1, R3, Q, J1, J2, J3, J4, J5, V, G and M have the meanings indicated in the claims.
Abstract: The present invention relates to compounds of the formulae (I) and (II), in which RO; R1; R3; Q; J1; J2; J3; J4; J5; V; G and M have the meanings indicated in the claims. The compounds of the formulae (I) and (II) are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formulae (I) and (II), their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.
TL;DR: In this article, a new concept for the separation of heterogeneous catalysts is presented, where surface modified catalysts are located only in one of two immiscible liquid phases.
Abstract: A new concept for the separation of heterogeneous catalysts is presented. Against gravity, surface modified catalysts are located only in one of two immiscible liquid phases. The catalyst phase can be separated by simple decantation. Advantages of this multiphase system were demonstrated for hydrogenations and CC coupling reactions.
01 Jan 2004
TL;DR: Meta-Analysen as discussed by the authors are meta-analyse empirischer befunde, i.e., the einzelnen publizierten empirischen Befundes aus Primar- oder Sekundaranalysen zusammenzufassen und mogliche Unterschiede in den Ergebnissen verschiedener Studien aufzuklaren.
Abstract: In der empirischen Sozialforschung unterscheidet man gewohnlich Primarvon Sekundaranalysen. Primaranalysen sind erstmalige Untersuchungen von Daten, die von Forschern selbst erhoben wurden, wahrend in Sekundaranalysen Datenmaterial herangezogen wird, das von anderen erhoben und in der Regel bereits ausgewertet wurde. Sekundaranalysen konnen sich auf die ursprunglichen oder auf neue Forschungsfragen richten (Friedrichs 1973; Schnell, Hill und Esser 1995: 238). In den letzten beiden Jahrzehnten hat sich nun ein dritter Typus empirischer Sozialforschung etabliert, der von Glass (1976) Meta-Analyse genannt wurde. Es handelt sich hierbei um die statistische Analyse empirischer Befunde, die aus voneinander unabhangigen Studien stammen. Meta-Analysen werden in der Regel mit dem Ziel vorgenommen, die einzelnen publizierten empirischen Befunde aus Primar- oder Sekundaranalysen zu einer Gesamtgrose zusammenzufassen und mogliche Unterschiede in den Ergebnissen verschiedener Studien aufzuklaren. Der Ausdruck Meta-Analyse ist bereits zu einem Sammelbegriff fur diverse Techniken zur Synthese empirischer Befunde geworden, deren Kritik und Weiterentwicklung mittlerweile einen eigenen Zweig in der sozialwissenschaftlichen Methodendiskussion ausmacht.
TL;DR: The attempt is made to connect prefrontal grey matter loss with post-mortem findings of reduced neuropil but preserved cytoarchitecture leading to recently described candidate genes and their function.
Abstract: Schizophrenia is a severe mental disorder with a relapsing long-term course in 80 % of the sufferers. The underlying neurobiological principles of the long-term course are widely unknown. Therefore an attempt is made to evaluate data from structural imaging and neuropsychology to shed some light on these mechanisms. Interestingly there was a significant correlation between length of illness and volume reduction in the prefrontal grey matter in schizophrenia. There was a lack of such a correlation for the whole brain volume, white matter volume or the grey matter volume outside the prefrontal lobe. Furthermore none of the neuropsychological measures correlated with length of illness. Both findings are supported by data from prospective studies up to five years demonstrating a significant loss of frontal grey matter volume, but no change of cognitive dysfunction in the course of time. The attempt is made to connect prefrontal grey matter loss with post-mortem findings of reduced neuropil but preserved cytoarchitecture leading to recently described candidate genes and their function.
01 Jan 2004
TL;DR: In this article, the Selektivitat der Wahrnehmung wird schon dadurch geradezu erzwungen, dass Jurgen Friedrichs mehr als 200 Publikationen aufzuweisen hat, darunter 18 Monographien und 21 herausgegebene Bande.
Abstract: Dieser Band ist Jurgen Friedrichs gewidmet, der mit 65 Jahren sein Emeritierungsalter erreicht hat. Es ist fast aussichtslos, sein uber Jahrzehnte gewachsenes Werk auf einen Begriff bringen zu wollen, zumal seine Publikationstatigkeit sicherlich nicht an ihr Ende gekommen ist. Ob ein Lebenswerk durch Grundideen, biographische Erfahrungen oder Zufalle einer akademischen Karriere gepragt wurde, wird nur der Betroffene selbst feststellen konnen. Jeder Versuch von Dritten, eine „innere Logik“ oder eine „innere Ordnung“ in einem Werk zu entdecken, erfordert eine Art synthetischer Abstraktion, die subjektiv und selektiv ist. Die Selektivitat der Wahrnehmung wird schon dadurch geradezu erzwungen, dass Jurgen Friedrichs mehr als 200 Publikationen aufzuweisen hat, darunter 18 Monographien und 21 herausgegebene Bande.
TL;DR: In this paper, the authors present an overview of the work of the FETZ-Therapiezentrum für psychische Krisen (FETZ) in terms of Beratung and behandlung bei erhöhtem psychoserisiko.
Abstract: 1Früherkennungsund Therapiezentrum für psychische Krisen – FETZ, Klinik für Psychiatrie und Psychotherapie, Klinikum der Universität zu Köln; 2Zentrum für Beratung und Behandlung bei erhöhtem Psychoserisiko – ZeBB, Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum Bonn; 3Früherkennungszentrum für psychische Krisen – FEZ, Klinik für Psychiatrie und Psychotherapie, Klinikum der HeinrichHeine-Universität Düsseldorf; 4Früherkennungsund Therapiezentrum für psychische Krisen – FETZ, Klinik für Psychiatrie und Psychotherapie, Klinikum der Ludwig-Maximilian-Universität München; 5Arbeitsgruppe Schizophrenie, Zentralinstitut für Seelische Gesundheit, Mannheim
01 Jan 2004
TL;DR: An arterial transfer function using aortic and peripheral blood pressure waves measured simultaneously in healthy children undergoing diagnostic catheterization is developed and applied to peripheralBlood pressure pulses measured during specific stages of sleep and at distinct points in the respiratory cycle to estimate the central aorta pressure wave shape.
Abstract: We have developed an arterial transfer function using aortic and peripheral blood pressure waves measured simultaneously in healthy children undergoing diagnostic catheterization We have applied this transfer function to peripheral blood pressure pulses measured during specific stages of sleep and at distinct points in the respiratory cycle in a different set of children with and without sleep disordered breathing to estimate the central aortic pressure wave shape
01 Jan 2004
TL;DR: A decline of prevalence over time in all populations has been proposed but not observed; this constellation is called the “paradox of schizophrenia”.
Abstract: As evidenced by a bulk 0of twin and family studies schizophrenia is clearly a genetically influenced disorder, with more than 50% of the etiological variance being due to genetic variation. This genetic diathesis has to be considered together with the preferential onset of the disorder in late adolescence and early adulthood, and the severe associated disability and impairment. On this basis a decline of prevalence over time in all populations has been proposed but not observed; this constellation is called the “paradox of schizophrenia”.
01 Jan 2004
TL;DR: Wagner et al. as discussed by the authors fuhrten wir eine Meta-Analyse aller deutschen Scheidungsstudien durch, in denen with Langsschnittdaten and quantitativen Verfahren die Determinanten der Ehestabilitat untersucht wurden.
Abstract: Die empirische Analyse von Scheidungsrisiken wird von der deutschen Familiensoziologie seit etwa 20 Jahren mit groser Intensitat betrieben. In keinem europaischen Land gibt es dazu mehr Studien und weltweit gibt es wohl nur in den USA eine umfangreichere Forschung als in Deutschland. In einer derartigen Situation kann und sollte man sich fragen, was diese Forschung erbracht hat. Um diese Frage zu beantworten, fuhrten wir eine Meta-Analyse aller deutschen Scheidungsstudien durch, in denen mit Langsschnittdaten und quantitativen Verfahren die Determinanten der Ehestabilitat untersucht wurden (Wagner/Weis 2003). Wir konnten 42 Publikationen ermitteln, in denen diese Determinanten in uberwiegend multivariaten Regressionsmodellen analysiert wurden. Die Determinanten lassen sich mehrheitlich zentralen Konzepten der mikrookonomischen Theorie und der Austauschtheorie zuordnen.