Impulsive traits and 5-HT2A receptor promoter polymorphism in alcohol dependents: Possible association but no influence of personality disorders

Objective: Impulsive behavior in alcoholics puts them at serious risk of severer course of disease and has been related to the serotonergic neurotransmission dysfunction. The aim of this study is to investigate the association between impulsive aggression in alcohol dependents with regard to the G-1438A polymorphism in the promoter region of the 5-HT2A receptor gene. Furthermore, we investigated the statistical interaction between 5-HT2A alleles, antisocial personality disorder (APD) and impulsive aggression in alcohol dependents. Alcohol dependents were investigated because these personality disorders and impulsive behavior are very frequent in alcohol dependence anf of clinical relevance. Methods: One hundred and thirty-five patients of German descent meeting DSM-IV criteria of alcohol dependence were recruited. Blood samples were taken from alcohol dependents to determine 5-HT2A promoter polymorphisms using PCR (polymerase chain reaction) of lymphocyte DNA. Impulsive aggression was assessed using a German version of the Barratt Impulsiveness Scale which was translated and backtranslated. Alcohol dependents were subdivided into low- or high-impulsivity groups using a median split of the Barratt score. APD and borderline personality disorder (BPD) were assessed using the SCID-II interview. Results: The low-impulsivity group was slightly older and showed a later age at alcoholism onset than the highly impulsive group. Alcohol dependents with high impulsive traits showed a significant association with 5-HT2A 1438 A alleles. After excluding alcohol dependents with APD or BPD from the analysis, this association remained significant. Furthermore, no association between APD, BPD and 5-HT2A alleles was noted. Conclusions: Inpatient alcohol dependents showed a significant association between 5-HT2A A alleles and impulsive traits, independent of the presence of APD or BPD. No association was noted between personality disorders and the polymorphism. This is the first report about an association of 5-HT2A promoter polymorphism and impulsive behavior in alcohol dependents. This finding may refer only to impulsive traits and may be independent of personality disorders in this sample. These results have to be confirmed in larger samples and in healthy control subjects to determine whether this association is of general validity. Copyright (C) 2001 S. Karger AG, Basel

Gewinne und Verluste von Arbeitsplätzen in Betrieben : der "Job-Turnover"-Ansatz

"Job-Turnover mißt den Umschlag von (besetzten) Arbeitsplätzen und damit, wie schnell sich der Bestand an Stellen erneuert. In Jahr-zu-Jahr-Analysen wird ausgewiesen: - um wieviel Prozent die Beschäftigung dadurch zunimmt, daß bestehende Betriebe ihre Beschäftigung ausweiten (Expansionsrate), - um wieviel Prozent die Beschäftigung dadurch abnimmt, daß bestehende Betriebe ihre Beschäftigung reduzieren (Schrumpfrate), - um wieviel Prozent die Beschäftigung dadurch ansteigt, daß neue Betriebe gegründet werden (Gründungsrate), - um wieviel Prozent sich die Beschäftigung dadurch vermindert, daß Betriebe schließen (Schließungsrate). Untersucht wird der 10-Jahres-Zeitraum 1977-1978, gegliedert nach neun Sektoren und 142 Arbeitsamtsbezirken. Als Datenquelle dient die Beschäftigungsstatistik der Bundesanstalt für Arbeit (sozialversicherungspflichtig Beschäftigte). Als Durchschnitt der 10 Vorjahresvergleiche 1977/78 - 1986/87 ergibt sich für die Expansions-, aber auch für die Schrumpfungsrate ein Wert von jeweils 6,1%. Ein Überschuß von Neugründungen gegenüber den Betriebsschließungen war praktisch in allen Regionen - von einzelnen Ausnahmen abgesehen - festzustellen. Das Nord-Süd-Gefälle in der Beschäftigungsentwicklung war das Ergebnis von positiven Salden aus Expansions- und Schrumpfungsraten im Süden und entsprechenden negativen Salden im Norden und Westen des Landes. Größere Turnover-Raten gab es in den vornehmlich kleinbetrieblich organisierten Dienstleistungsbetrieben, während der Stellenumschlag im sekundären Sektor (mit überwiegend größeren Betrieben) unterdurchschnittlich blieb. Als wirtschaftspolitische Konsequenzen aus den empirischen Ergebnissen werden im letzten Absatz der Arbeit neben der Förderung von Existenzgründungen auch die Stützung der Lebensfähigkeit von relativ jungen Kleinbetrieben und die Notwendigkeit von berufsbildenden Schulungs- und Ausbildungsmaßnahmen für freigesetzte Arbeitskräfte abgeleitet." (Autorenrferat)job turnover, Arbeitsplätze, Betrieb

Effect of Early High-Dose Recombinant Human Erythropoietin on Behavior and Quality of Life in Children Aged 5 Years Born Very Preterm: Secondary Analysis of a Randomized Clinical Trial

IMPORTANCE In light of the promising neuroprotective properties of recombinant human erythropoietin (RHEpo), the Swiss EPO Neuroprotection Trial was started to investigate its effect on neurodevelopment in very preterm infants. The results of the primary and secondary outcome analysis did not show any effect of RHEpo on cognitive performance, neuromotor outcomes, or somatic growth of the study participants at ages 2 or 5 years. OBJECTIVE To investigate whether early high-dose RHEpo improves behavioral outcomes and health-related quality of life (HRQoL) at age 5 years. DESIGN, SETTING, AND PARTICIPANTS This was a prespecified secondary analysis of the double-blind, placebo-controlled, multicenter Swiss EPO Neuroprotection randomized clinical trial, which was conducted at 5 level-III perinatal centers in Switzerland. Infants born between 26 weeks 0 days' and 31 weeks 6 days' gestation were recruited between 2005 and 2012 and followed-up until age 5 years (last follow-up in 2018). Data were analyzed from January 6 to December 31, 2021. INTERVENTIONS Infants were assigned to receive either RHEpo (3000 IU/kg) or placebo (saline, 0.9%) intravenously 3 times within the first 42 hours after birth. MAIN OUTCOMES AND MEASURES The prespecified parent-reported measures of behavioral outcomes and health-related quality of life (HRQoL) of their children at the age of 5 years were assessed by two standardized questionnaires: the Strengths and Difficulties Questionnaire (behavioral outcomes) and the KIDSCREEN-27 (HRQoL). RESULTS Among 448 randomized infants, 228 infants were assigned to the RHEpo group and 220 infants were assigned to the placebo group. Questionnaire data were available for 317 children (71%) at a mean (SD) age of 5.8 (0.4) years (mean [SD] gestational age at birth, 29.3 [1.6] weeks; mean [SD] birth weight 1220 [340] grams; 128 [40%] female infants). At the age 5 years follow-up, the mean (SD) total difficulties score in the RHEpo group (8.41 [5.60] points) was similar to that of the placebo group (7.76 [4.81]) (P = .37). There were no statistically significant differences between the groups in any other outcome measures. CONCLUSIONS AND RELEVANCE This secondary analysis of a randomized clinical trial showed no evidence for an effect of early high-dose RHEpo administration on behavioral outcomes or HRQoL in children born very preterm at early school age. TRIAL REGISTRATION - ClinicalTrials.gov Identifier: NCT00413946

Therapy Development for Epidermolysis Bullosa

Although rare genodermatoses such as Epidermolysis bullosa have received more attention over the last years, no approved treatment options targeting causal mutations are currently available. Still, such diseases can be devastating, in some cases even associated with life-threatening secondary manifestations. Therefore, developing treatments that target disease-associated complications along with causal therapies remains the focus of current research efforts, in order to increase patient’s quality of life and potentially their life expectancy. Epidermolysis bullosa is a genodermatosis that is caused by mutations in either one of 16 genes, predominantly encoding structural components of the skin and mucosal epithelia that are crucial to give these barrier organs physical and mechanical resilience to stress. The genetic heterogeneity of the disease is recapitulated in the high variability of phenotypic expressivity observed, ranging from minor and localized blistering to generalized erosions and wound chronification, rendering certain subtypes a systemic disease that is complicated by a plethora of secondary manifestations. During the last decades, several studies have focused on developing treatments for EB patients and significant progress has been made, as reflected by numerous publications, patents, and registered trials available. Overall, strategies range from causal to symptom-relieving approaches, and include gene, RNA and cell therapies, as well as drug developments based on biologics and small molecules. In this chapter, we highlight the most recent and promising approaches that are currently being investigated in order to provide effective treatments for patients with epidermolysis bullosa in the future

Minimally invasive, imaging guided virtual autopsy compared to conventional autopsy in foetal, newborn and infant cases: study protocol for the paediatric virtual autopsy trial

BACKGROUND: In light of declining autopsy rates around the world, post-mortem MR imaging is a promising alternative to conventional autopsy in the investigation of infant death. A major drawback of this non-invasive autopsy approach is the fact that histopathological and microbiological examination of the tissue is not possible. The objective of this prospective study is to compare the performance of minimally invasive, virtual autopsy, including CT-guided biopsy, with conventional autopsy procedures in a paediatric population. METHODS/DESIGN: Foetuses, newborns and infants that are referred for autopsy at three different institutions associated with the University of Zurich will be eligible for recruitment. All bodies will be examined with a commercial CT and a 3 Tesla MRI scanner, masked to the results of conventional autopsy. After cross-sectional imaging, CT-guided tissue sampling will be performed by a multifunctional robotic system (Virtobot) allowing for automated post-mortem biopsies. Virtual autopsy results will be classified with regards to the likely final diagnosis and major pathological findings and compared to the results of conventional autopsy, which remains the diagnostic gold standard. DISCUSSION: There is an urgent need for the development of alternative post-mortem examination methods, not only as a counselling tool for families and as a quality control measure for clinical diagnosis and treatment but also as an instrument to advance medical knowledge and clinical practice. This interdisciplinary study will determine whether virtual autopsy will narrow the gap in information between non-invasive and traditional autopsy procedures. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01888380

MNPBEM - A Matlab toolbox for the simulation of plasmonic nanoparticles

MNPBEM is a Matlab toolbox for the simulation of metallic nanoparticles (MNP), using a boundary element method (BEM) approach. The main purpose of the toolbox is to solve Maxwell's equations for a dielectric environment where bodies with homogeneous and isotropic dielectric functions are separated by abrupt interfaces. Although the approach is in principle suited for arbitrary body sizes and photon energies, it is tested (and probably works best) for metallic nanoparticles with sizes ranging from a few to a few hundreds of nanometers, and for frequencies in the optical and near-infrared regime. The toolbox has been implemented with Matlab classes. These classes can be easily combined, which has the advantage that one can adapt the simulation programs flexibly for various applications.Comment: to appear in Comp. Phys. Commun.; see also http://physik.uni-graz.at/~uxh/mnpbem/mnpbem.htm

Intradermal Indocyanine Green for In Vivo Fluorescence Laser Scanning Microscopy of Human Skin: A Pilot Study

BACKGROUND: In clinical diagnostics, as well as in routine dermatology, the increased need for non-invasive diagnosis is currently satisfied by reflectance laser scanning microscopy. However, this technique has some limitations as it relies solely on differences in the reflection properties of epidermal and dermal structures. To date, the superior method of fluorescence laser scanning microscopy is not generally applied in dermatology and predominantly restricted to fluorescein as fluorescent tracer, which has a number of limitations. Therefore, we searched for an alternative fluorophore matching a novel skin imaging device to advance this promising diagnostic approach. METHODOLOGY/PRINCIPAL FINDINGS: Using a Vivascope®-1500 Multilaser microscope, we found that the fluorophore Indocyanine-Green (ICG) is well suited as a fluorescent marker for skin imaging in vivo after intradermal injection. ICG is one of few fluorescent dyes approved for use in humans. Its fluorescence properties are compatible with the application of a near-infrared laser, which penetrates deeper into the tissue than the standard 488 nm laser for fluorescein. ICG-fluorescence turned out to be much more stable than fluorescein in vivo, persisting for more than 48 hours without significant photobleaching whereas fluorescein fades within 2 hours. The well-defined intercellular staining pattern of ICG allows automated cell-recognition algorithms, which we accomplished with the free software CellProfiler, providing the possibility of quantitative high-content imaging. Furthermore, we demonstrate the superiority of ICG-based fluorescence microscopy for selected skin pathologies, including dermal nevi, irritant contact dermatitis and necrotic skin. CONCLUSIONS/SIGNIFICANCE: Our results introduce a novel in vivo skin imaging technique using ICG, which delivers a stable intercellular fluorescence signal ideal for morphological assessment down to sub-cellular detail. The application of ICG in combination with the near infrared laser opens new ways for minimal-invasive diagnosis and monitoring of skin disorders

The added value of participatory modelling in fisheries management – what has been learnt?

How can uncertain fisheries science be linked with good governance processes, thereby increasing fisheries management legitimacy and effectiveness? Reducing the uncertainties around scientific models has long been perceived as the cure of the fisheries management problem. There is however increasing recognition that uncertainty in the numbers will remain. A lack of transparency with respect to these uncertainties can damage the credibility of science. The EU Commission's proposal for a reformed Common Fisheries Policy calls for more self-management for the fishing industry by increasing fishers' involvement in the planning and execution of policies and boosting the role of fishers' organisations. One way of higher transparency and improved participation is to include stakeholders in the modelling process itself. The JAKFISH project (Judgment And Knowledge in Fisheries Involving StakeHolders) invited fisheries stakeholders to participate in the process of framing the management problem, and to give input and evaluate the scientific models that are used to provide fisheries management advice. JAKFISH investigated various tools to assess and communicate uncertainty around fish stock assessments and fisheries management. Here, a synthesis is presented of the participatory work carried out in four European fishery case studies (Western Baltic herring, North Sea Nephrops, Central Baltic Herring and Mediterranean swordfish), focussing on the uncertainty tools used, the stakeholders' responses to these, and the lessons learnt. It is concluded that participatory modelling has the potential to facilitate and structure discussions between scientists and stakeholders about uncertainties and the quality of the knowledge base. It can also contribute to collective learning, increase legitimacy, and advance scientific understanding. However, when approaching real-life situations, modelling should not be seen as the priority objective. Rather, the crucial step in a science–stakeholder collaboration is the joint problem framing in an open, transparent way

Interrupted time series study found mixed effects of the impact of the Bavarian smoke-free legislation on pregnancy outcomes

In 2007 the German government passed smoke-free legislation, leaving the details of implementation to the individual federal states. In January 2008 Bavaria implemented one of the strictest laws in Germany. We investigated its impact on pregnancy outcomes and applied an interrupted time series (ITS) study design to assess any changes in preterm birth, small for gestational age (primary outcomes), and low birth weight, stillbirth and very preterm birth. We included 1,236,992 singleton births, comprising 83,691 preterm births and 112,143 small for gestational age newborns. For most outcomes we observed unclear effects. For very preterm births, we found an immediate drop of 10.4% (95%CI − 15.8, − 4.6%; p = 0.0006) and a gradual decrease of 0.5% (95%CI − 0.7, − 0.2%, p = 0.0010) after implementation of the legislation. The majority of subgroup and sensitivity analyses confirm these results. Although we found no statistically significant effect of the Bavarian smoke-free legislation on most pregnancy outcomes, a substantial decrease in very preterm births was observed. We cannot rule out that despite our rigorous methods and robustness checks, design-inherent limitations of the ITS study as well as country-specific factors, such as the ambivalent German policy context have influenced our estimation of the effects of the legislation