Neurobiologische Untersuchungen zur Rolle von Dopamin bei risikoabhängigem Entscheidungsverhalten

Um das Überleben in einer sich ständig ändernden Umwelt zu sichern, müssen Menschen und Tiere tagtäglich eine Vielzahl von Kosten-Nutzen-abhängigen Entscheidungen fällen. Das Ziel dieses Entscheidungsprozesses ist es, eine situationsgerecht optimale Entscheidung zu treffen, bei der mit möglichst geringen Kosten der Nutzen maximiert wird. Der Präfrontalcortex (PFC) und der Nucleus Accumbens (Acb) sind die Schlüsselstrukturen eines neuralen Netzwerkes, welches eine wichtige Kategorie von Kosten-Nutzen-abhängigen Entscheidungen steuert, nämlich sogenannte risikoabhängige Entscheidungen. Beide Strukturen empfangen Dopamin-Signale aus dem Mittelhirn, die Informationen über Kosten und Nutzen kodieren. Das Ziel meiner Arbeit bestand darin, die noch unbekannte kausale Bedeutung von Dopamin-Signalen im PFC und im Acb bei risikoabhängigem Entscheidungsverhalten zu verstehen. Im Rahmen meiner Arbeit wurde das risikoabhängige Entscheidungsverhalten von Ratten beim Durchführen von Risikoaufgaben in Skinner-Boxen untersucht. Dabei hatte das Tier die Wahl zwischen zwei Hebeln. Bei dem „sicheren Hebel“ führte ein Hebeldruck sicher zu einer geringen Futterbelohnung. Bei dem „riskanten Hebel“ führte ein Hebeldruck entweder zu einer hohen oder gar keiner Futterbelohnung. Die Belohnungswahrscheinlichkeit, also die Wahrscheinlichkeit beim riskanten Hebel eine hohe Futterbelohnung zu erhalten, nahm entweder zwischen verschiedenen Sitzungen (konstante Risikoaufgabe) oder innerhalb einer Sitzung (absteigende Risikoaufgabe) ab. Aus meinen Messungen mit der konstanten Risikoaufgabe geht hervor, dass die permanente Inaktivierung der Dopamin-Innervation der orbitalen Subareale des PFC (OFC) sowie der Core- und Shell-Subareale des Acb (AcbC und AcbS) das risikoabhängige Entscheidungsverhalten nicht beeinträchtigt. Diese Befunde ließen sich in nachfolgenden Untersuchungen mit der absteigenden Risikoaufgabe erhärten: Tiere mit einer Blockade der Dopamin D1- und D2-Rezeptoraktivität des OFC beziehungsweise des Acb waren unverändert sensitiv gegenüber der abnehmenden Belohnungswahrscheinlichkeit. Allerdings war unter Blockade der D1- und D2-Rezeptoraktivität im AcbC die generelle Präferenz für die riskante Handlungsoption signifikant verringert. Dopamin-Signale im PFC und im Acb scheinen also nicht an der Erfassung des Risikos und dessen Veränderung beteiligt zu sein. Meine Daten sprechen vielmehr dafür, dass die Dopamin-Rezeptoraktivität im AcbC die generelle Präferenz für riskante Handlungsoptionen reguliert. Die dem risikoabhängigem Entscheidungsverhalten zugrunde liegende Neurobiologie ist komplex und die Datenlage teilweise uneinheitlich. Ein wesentlicher Grund dafür sind die in der Literatur verwendeten verschiedenartigen Risikoaufgaben, die auf unterschiedlichen Risikokonzepten basieren. Aus diesem Grund unterscheiden sich sowohl die erforderlichen kognitiven Leistungen als auch die beteiligten neuralen Schaltkreise in den verschiedenen Risikoaufgaben und die Effekte von dopaminergen Manipulationen sind teilweise inkonsistent. Meine Befunde sprechen dafür, dass Dopamin-Signale im AcbC die Präferenz von Tieren für Handlungsoptionen steigern, die trotz eines hohen Risikos mit hohem Nutzen verbunden sind. Bei den hier untersuchten risikoabhängigen Entscheidungen unterstützen die Dopamin-Signale im AcbC demnach nicht die Risikoerfassung an sich, sondern sie verstärken generell die Präferenz für kostenintensive Handlungsoptionen, die mit einer höheren, riskanten Belohnung verknüpft sind. Möglicherweise führt eine solche Dopamin-vermittelte Regulation von Handlungspräferenzen zu einer höheren biologischen Fitness und bildet damit einen Selektionsvorteil. Die Daten stehen im Einklang mit klinischen Befunden, wonach Suchtmittel und Medikamente, welche die Dopamin-Transmission erhöhen, riskante Entscheidungen des Menschen fördern. Meine Daten zeigen, dass der AcbC eine der Strukturen zu sein scheint, welche diese Wirkungen vermittelt

Health sector involvement in the management of female genital mutilation/cutting in 30 countries

Background: For the last decades, the international community has emphasised the importance of a multisectoral approach to tackle female genital mutilation (FGM/C). While considerable improvement concerning legislations and community involvement is reported, little is known about the involvement of the health sector. Method: A mixed methods approach was employed to map the involvement of the health sector in the management of FGM/C both in countries where FGM/C is a traditional practice (countries of origin), and countries where FGM/C is practiced mainly by migrant populations (countries of migration). Data was collected in 2016 using a pilot-tested questionnaire from 30 countries (11 countries of origin and 19 countries of migration). In 2017, interviews were conducted to check for data accuracy and to request relevant explanations. Qualitative data was used to elucidate the quantitative data. Results: A total of 24 countries had a policy on FGM/C, of which 19 had assigned coordination bodies and 20 had partially or fully implemented the plans. Nevertheless, allocation of funding and incorporation of monitoring and evaluation systems was lacking in 11 and 13 of these countries respectively. The level of the health sectors' involvement varied considerably across and within countries. Systematic training of healthcare providers (HCP) was more prevalent in countries of origin, whereas involvement of HCP in the prevention of FGM/C was more prevalent in countries of migration. Most countries reported to forbid HCP from conducting FGM/C on both minors and adults, but not consistently forbidding re-infibulation. Availability of healthcare services for girls and women with FGM/C related complications also varied between countries dependent on the type of services. Deinfibulation was available in almost all countries, while clitoral reconstruction and psychological and sexual counselling were available predominantly in countries of migration and then in less than half the countries. Finally, systematic recording of FGM/C in medical records was completely lacking in countries of origin and very limited in countries of migration. Conclusion: Substantial progress has been made in the involvement of the health sector in both the treatment and prevention of FGM/C. Still, there are several areas in need for improvement, particularly monitoring and evaluatio

Dopamine D1/D2 receptor activity in the nucleus accumbens core but not in the nucleus accumbens shell and orbitofrontal cortex modulates risk-based decision making

Background: It is well known that brain dopamine (DA) signals support risk-based decision making; however, the specific terminal regions of midbrain DA neurons through which DA signals mediate risk-based decision making are unknown. Methods: Using microinfusions of the D1/D2 receptor antagonist flupenthixol, we sought to explore the role of D1/D2 receptor activity in the rat orbitofrontal cortex (OFC) and core and shell regions of the nucleus accumbens (AcbC and AcbS, respectively) in the regulation of risky choices. A risk-discounting task was used that involves choices between a certain small-reward lever that always delivered 1 pellet or a risky large-reward lever which delivered 4 pellets but had a decreasing probability of receiving the reward across 4 subsequent within-session trial blocks (100%, 50%, 25%, 12.5%). To validate task sensitivity to experimental manipulations of DA activity, we also examined the effects of systemic amphetamine and flupenthixol. Results: Systemic amphetamine increased while systemic flupenthixol reduced risky choices. Results further demonstrate that rats that received intra-AcbC flupenthixol were able to track increasing risk associated with the risky lever but displayed a generally reduced preference for the risky lever across all trial blocks, including in the initial trial block (large reward at 100%). Microinfusions of flupenthixol into the AcbS or OFC did not alter risk-based decision making. Conclusions: Our data suggest that intra-AcbC D1/D2 receptor signaling does not support the ability to track shifts in reward probabilities but does bias risk-based decision making. That is, it increased the rats’ preference for the response option known to be associated with higher risk-related costs

Human-Automation Allocations for Current Robotic Space Operations

Within the Human Research Program, one risk delineates the uncertainty surrounding crew working with automation and robotics in spaceflight. The Risk of Inadequate Design of Human and Automation/Robotic Integration (HARI) is concerned with the detrimental effects on crew performance due to ineffective user interfaces, system designs and/or functional task allocation, potentially compromising mission success and safety. Risk arises because we have limited experience with complex automation and robotics. One key gap within HARI, is the gap related to functional allocation. The gap states: We need to evaluate, develop, and validate methods and guidelines for identifying human-automation/robot task information needs, function allocation, and team composition for future long duration, long distance space missions. Allocations determine the human-system performance as it identifies the functions and performance levels required by the automation/robotic system, and in turn, what work the crew is expected to perform and the necessary human performance requirements. Allocations must take into account each of the human, automation, and robotic systems capabilities and limitations. Some functions may be intuitively assigned to the human versus the robot, but to optimize efficiency and effectiveness, purposeful role assignments will be required. The role of automation and robotics will significantly change in future exploration missions, particularly as crew becomes more autonomous from ground controllers. Thus, we must understand the suitability of existing function allocation methods within NASA as well as the existing allocations established by the few robotic systems that are operational in spaceflight. In order to evaluate future methods of robotic allocations, we must first benchmark the allocations and allocation methods that have been used. We will present 1) documentation of human-automation-robotic allocations in existing, operational spaceflight systems; and 2) To gather existing lessons learned and best practices in these role assignments, from spaceflight operational experience of crew and ground teams that may be used to guide development for future systems. NASA and other space agencies have operational spaceflight experience with two key Human-Automation-Robotic (HAR) systems: heavy lift robotic arms and planetary robotic explorers. Additionally, NASA has invested in high-fidelity rover systems that can carry crew, building beyond Apollo's lunar rover. The heavy lift robotic arms reviewed are: Space Station Remote Manipulator System (SSRMS), Japanese Remote Manipulator System (JEMRMS), and the European Robotic Arm (ERA, designed but not deployed in space). The robotic rover systems reviewed are: Mars Exploration Rovers, Mars Science Laboratory rover, and the high-fidelity K10 rovers. Much of the design and operational feedback for these systems have been communicated to flight controllers and robotic design teams. As part of the mitigating the HARI risk for future human spaceflight operations, we must document function allocations between robots and humans that have worked well in practice

Attachment style contributes to the outcome of a multimodal lifestyle intervention

<p>Abstract</p> <p>Background & Aims</p> <p>The long-term success of life-style interventions in the treatment of obesity is limited. Although psychological factors have been suggested to modify therapeutic effects, specifically the implications of attachment styles and the patient-therapist relationship have not been examined in detail yet.</p> <p>Methods</p> <p>This study included 44 obese patients who participated in a one-year multimodal weight-reduction program. Attachment style was analyzed by the Adult Attachment Prototype Rating (AAPR) inventory and its relation to a one-year weight reduction program was studied. The patient-therapist-relationship was assessed using the Helping Alliance Questionnaire.</p> <p>Results</p> <p>Attachment style was secure in 68% of participants and insecure (preoccupied and dismissing) in 32%. Interestingly a significantly higher weight-reduction was found in securely (SAI) compared to insecurely attached individuals (UAI; p < 0.05). This estimation correlated positively also to the quality of helping alliance (p = 0.004).</p> <p>Conclusions</p> <p>The frequency of insecure attachment in obese individuals was comparable to that of the normal population. Our data suggest a greater weight-reduction for SAI than for UAI, and the patient-therapist relationship was rated more positively. The conclusion can be drawn that a patient's attachment style plays a role in an interdisciplinary treatment program for obesity and has an influence on the effort to lose weight.</p

Self-reported TV and computer time do not represent accelerometer-derived total sedentary time in 10 to 12-year-olds

Screen-time activities are often used as proxies for sedentary time. We studied associations of self-reported television (TV), computer and total screen-time with accelerometer-derived total sedentary time in European children (10-12 years). Analyses showed significant positive associations between TV, computer and total screen-time with total sedentary time for the total sample, however, the explained variance was low and stratified analyses only revealed a significant positive association between total screen-time and total sedentary time in boys and between computer time and total sedentary time in Dutch children. This suggests that self-reported TV and computer time do not adequately reflect total sedentary time in schoolchildre

Using Predictive Model for Strategic Control of Multi-reservoir System Storage Capacity

AbstractThe paper will describe the algorithm based on adaptive optimization of multi reservoir control, which the medium-term water flow predictions into the reservoirs for several months ahead repeatedly use. Hydrological prediction model was created using ANN method and values of control outflows are searching by optimization based on evolutionary algorithms optimization technique. The objective function was descripted as the sum of squares deviations between required and actual controlled water outflow from reservoirs where objective function is minimized. The algorithm of adaptive control is applied to the operation storage control of selected reservoir system, which open water reservoirs Vir and Brno are created

Screen-based sedentary time: Association with soft drink consumption and the moderating effect of parental education in European children: The ENERGY study

AIM: The aim of the present study was to explore if children who spend more time on screen-based sedentary behaviors (i.e.TV viewing and computer use) drink more sugar-sweetened soft drinks. The study also assessed whether these associations were independent of individual and home environmental correlates of soft drink consumption and whether they were moderated by parental education. METHODS: Data were collected from 7886 children participating in the EuropeaN Energy balance Research to prevent excessive weight Gain among Youth (ENERGY) survey conducted in eight European countries. Self-report questionnaires were used. Multilevel linear regression analyses with soft drink consumption as dependent variable, TV viewing and computer use as independent variables and age, gender, parental education, attitude towards soft drinks, self-efficacy, parental modelling, parental rules and home availability of soft drinks as covariates were conducted. Further interactions were tested to explore if these associations were moderated by parental education. Country-specific analyses were conducted. RESULTS: In six of the eight included countries, a significant positive association was observed between TV viewing (min/day) and soft drink consumption (ml/day), independent of individual and home environmental correlates of soft drink consumption (B = 0.46 (0.26-0.66) in Greece, B = 0.77 (0.36-1.17) in Norway, B = 0.82 (0.12-1.51) in Hungary, B = 1.06 (0.67-1.46) in Spain, B = 1.21 (0.67-1.74) in Belgium and B = 1.49 (0.72-2.27) in Switzerland). There was no significant association between computer use and soft drink consumption in six of the eight included countries in the final models. Moderation effects of parental education in the association between TV viewing and soft drink consumption were found in Norway and Hungary, the association being stronger among those with low parental education. CONCLUSIONS: TV viewing appears to be independently associated with soft drink consumption and this association was moderated by parental education in two countries only. Reducing TV time might therefore favorably impact soft drink consumption

Protein phosphorylation and its role in archaeal signal transduction

Reversible protein phosphorylation is the main mechanism of signal transduction that enables cells to rapidly respond to environmental changes by controlling the functional properties of proteins in response to external stimuli. However, whereas signal transduction is well studied in Eukaryotes and Bacteria, the knowledge in Archaea is still rather scarce. Archaea are special with regard to protein phosphorylation, due to the fact that the two best studied phyla, the Euryarchaeota and Crenarchaeaota, seem to exhibit fundamental differences in regulatory systems. Euryarchaeota (e.g. halophiles, methanogens, thermophiles), like Bacteria and Eukaryotes, rely on bacterial-type two-component signal transduction systems (phosphorylation on His and Asp), as well as on the protein phosphorylation on Ser, Thr and Tyr by Hanks-type protein kinases. Instead, Crenarchaeota (e.g. acidophiles and (hyper)thermophiles) only depend on Hanks-type protein phosphorylation. In this review, the current knowledge of reversible protein phosphorylation in Archaea is presented. It combines results from identified phosphoproteins, biochemical characterization of protein kinases and protein phosphatases as well as target enzymes and first insights into archaeal signal transduction by biochemical, genetic and polyomic studie

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London