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BACKGROUND: Pavlovian-to-instrumental transfer (PIT) describes the influence of conditioned stimuli on instrumental behaviors and is discussed as a key process underlying substance abuse. Here, we tested whether neural responses during alcohol-related PIT predict future relapse in alcohol-dependent patients and future drinking behavior in adolescents. METHODS: Recently detoxified alcohol-dependent patients (n = 52) and young adults without dependence (n = 136) underwent functional magnetic resonance imaging during an alcohol-related PIT paradigm, and their drinking behavior was assessed in a 12-month follow-up. To predict future drinking behavior from PIT activation patterns, we used a multivoxel classification scheme based on linear support vector machines. RESULTS: When training and testing the classification scheme in patients, PIT activation patterns predicted future relapse with 71.2% accuracy. Feature selection revealed that classification was exclusively based on activation patterns in medial prefrontal cortex. To probe the generalizability of this functional magnetic resonance imaging-based prediction of future drinking behavior, we applied the support vector machine classifier that had been trained on patients to PIT functional magnetic resonance imaging data from adolescents. An analysis of cross-classification predictions revealed that those young social drinkers who were classified as abstainers showed a greater reduction in alcohol consumption at 12-month follow-up than those classified as relapsers (Delta = -24.4 +/- 6.0 g vs. -5.7 +/- 3.6 g; p = .019). CONCLUSIONS: These results suggest that neural responses during PIT could constitute a generalized prognostic marker for future drinking behavior in established alcohol use disorder and in at-risk states.
I. Gründung, Aufgaben und Struktur des Hochkommissariats
II. Zur Rolle des OHCHR im und gegenüber dem Menschenrechtsrat
III. Zu Erfolgschancen von Feldmissionen in eher schwierigen Ländern: China, Russische Föderation, Afghanistan, Sudan und Kolumbien
IV. Zur Frage der politischen Unabhängigkeit des OHCHR
V. Schlussfolgerungen und Ausblick
We used single-molecule FRET in combination with other biophysical methods and molecular simulations to investigate the effect of temperature on the dimensions of unfolded proteins. With singlemolecule FRET, this question can be addressed even under nearnative conditions, where most molecules are folded, allowing us to probe a wide range of denaturant concentrations and temperatures. We find a compaction of the unfolded state of a small cold shock protein with increasing temperature in both the presence and the absence of denaturant, with good agreement between the results from single-molecule FRET and dynamic light scattering. Although dissociation of denaturant from the polypeptide chain with increasing temperature accounts for part of the compaction, the results indicate an important role for additional temperaturedependent interactions within the unfolded chain. The observation of a collapse of a similar extent in the extremely hydrophilic, intrinsically disordered protein prothymosin suggests that the hydrophobic effect is not the sole source of the underlying interactions. Circular dichroism spectroscopy and replica exchange molecular dynamics simulations in explicit water show changes in secondary structure content with increasing temperature and suggest a contribution of intramolecular hydrogen bonding to unfolded state collapse.
Introduction: Cardiac rehabilitation is designed for patients suffering from cardiovascular diseases or functional disabilities. The aim of a cardiac rehabilitation is to improve overall physical health, psychological well-being, physical function, the ability to participate in social life and help patients to change their habits. Regarding the heterogeneity of these aims measuring of the effect of cardiac rehabilitation is still a challenge. This study recommends a concept to assess the effects of cardiac rehabilitation regarding the individual change of relevant quality indicators.
Methods: With EVA-Reha; cardiac rehabilitation the Medical Advisory Service of Statutory Health Insurance Funds in Rhineland-Palatinate, Alzey (MDK Rheinland-Pfalz) developed a software to collect data set including sociodemographic and diagnostic data and also the results of specific assessments. The project was funded by the Techniker Krankenkasse, Hamburg, and supported by participating rehabilitation centers. From 01. July 2010 to 30. June 2011 1309 patients (age 71.5 years, 76.1% men) from 13 rehabilitation centers were consecutively enrolled. 13 quality indicators in 3 scales were developed for evaluation of cardiac rehabilitation: 1) cardiovascular risk factors (blood pressure, LDL cholesterol, triglycerides), 2) exercise capacity (resting heart rate, maximal exercise capacity, maximal walking distance, heart failure [NYHA classification], and angina pectoris [CCS classification]) and 3) subjective health (IRES-24: pain, somatic health, psychological wellbeing and depression as well as anxiety on the HADS). The study was prospective; data of patients were assessed at entry and discharge of rehabilitation. To measure the success of rehabilitation each parameter was graded in severity classes at entry and discharge. For each of the 13 quality indicators changes of severity class were rated in a rating matrix. For indicators without a requirement for medical care neither at entry nor at discharge no rating was performed.
Results: The grading into severity classes as well as the minimal important differences were given for the 13 quality indicators. The result of rehabilitation can be demonstrated in suitable form by means of rating of the 13 quality indicators according to a clinical population. The rating model differs well between clinically changed and unchanged patients for the quality indicators.
Conclusion: The result of cardiac rehabilitation can be assessed with 13 quality indicators measured at entry and discharge of the rehabilitation program. If a change into a more favorable category at the end of rehabilitation could be achieved it was counted as a success. The 13 quality indicators can be used to assess the individual result as well as the result of a population - e.g. all patients of a clinic in a specific time period. In addition, the assessment and rating of relevant quality indicators can be used for comparisons of rehabilitation centers.
The Richardson-Lucy deconvolution algorithm was applied to astronomical images in the very high-energy regime with photon energies above 100 GeV. Through a systematic study with respect to source significance, background level and source morphology we were able to derive optimal deconvolution parameters. The results presented show that deconvolution makes it possible to study structural details well below the angular resolution of the very high-energy gamma-ray experiment. (C) 2012 Elsevier B.V. All rights reserved.
Background Exercise rehabilitation is highly recommended by current guidelines on prevention of cardiovascular disease, but its implementation is still poor. Many clinicians experience difficulties in prescribing exercise in the presence of different concomitant cardiovascular diseases and risk factors within the same patient. It was aimed to develop a digital training and decision support system for exercise prescription in cardiovascular disease patients in clinical practice: the European Association of Preventive Cardiology Exercise Prescription in Everyday Practice and Rehabilitative Training (EXPERT) tool. Methods EXPERT working group members were requested to define (a) diagnostic criteria for specific cardiovascular diseases, cardiovascular disease risk factors, and other chronic non-cardiovascular conditions, (b) primary goals of exercise intervention, (c) disease-specific prescription of exercise training (intensity, frequency, volume, type, session and programme duration), and (d) exercise training safety advices. The impact of exercise tolerance, common cardiovascular medications and adverse events during exercise testing were further taken into account for optimized exercise prescription. Results Exercise training recommendations and safety advices were formulated for 10 cardiovascular diseases, five cardiovascular disease risk factors (type 1 and 2 diabetes, obesity, hypertension, hypercholesterolaemia), and three common chronic non-cardiovascular conditions (lung and renal failure and sarcopaenia), but also accounted for baseline exercise tolerance, common cardiovascular medications and occurrence of adverse events during exercise testing. An algorithm, supported by an interactive tool, was constructed based on these data. This training and decision support system automatically provides an exercise prescription according to the variables provided. Conclusion This digital training and decision support system may contribute in overcoming barriers in exercise implementation in common cardiovascular diseases.
Die zwölfte Konferenz des Forschungskreises Vereinte Nationen wurde am 28. Juni 2014 an der Universität Potsdam veranstaltet und stand unter dem Thema „Konzepte für die Reform der Vereinten Nationen“. Dabei wurde das komplexe Verhältnis zwischen Reformnotwendigkeit und Machbarkeitserwartungen einerseits und ausgebliebenen weitreichenden Strukturreformen und erfolgten „kleineren“, pragmatischen Reformschritten andererseits deutlich. Mit den vier Referaten stellte die Konferenz in der Tradition der Potsdamer UNO-Konferenzen die Verbindung von Wissenschaft und Praxis unter Beteiligung unterschiedlicher Disziplinen her.
Mit der Broschüre soll allen Interessierten die Möglichkeit gegeben werden, Einblick in ausgewählte Schwerpunkte der Reformdiskussion zu erhalten:
An ein Grundsatzreferat zu bisherigen Reformprozessen im UN-System insgesamt schließen sich drei Texte an, die das Verhältnis zwischen den Vereinten Nationen und den nichtstaatlichen Akteuren in den Blick nehmen, die relativ neue Institution des Menschenrechtsrates als Teil der Reformbemühungen betrachten und schließlich Ergebnisse und Trends bei den Reformen der Arbeitsmethoden des Sicherheitsrates erörtern.
Aus dem Inhalt:
- 10 Jahre Responsibility to Protect: Ein Sieg für die Menschenrechte? – Eine politik- und rechtswissenschaftliche Analyse
- Neue Regeln zur Abwesenheit des Angeklagten vor dem IStGH:
Menschenrechtliche Anforderungen an In-absentia-Verfahren
- EGMR: S.A.S. ./. Frankreich – Urteilsbesprechung zum Burkaverbot
The Low Earth Orbit (LEO) experiment Biology and Mars Experiment (BIOMEX) is an interdisciplinary and international space research project selected by ESA. The experiment will be accommodated on the space exposure facility EXPOSE-R2 on the International Space Station (ISS) and is foreseen to be launched in 2013. The prime objective of BIOMEX is to measure to what extent biomolecules, such as pigments and cellular components, are resistant to and able to maintain their stability under space and Mars-like conditions. The results of BIOMEX will be relevant for space proven biosignature definition and for building a biosignature data base (e.g. the proposed creation of an international Raman library). The library will be highly relevant for future space missions such as the search for life on Mars. The secondary scientific objective is to analyze to what extent terrestrial extremophiles are able to survive in space and to determine which interactions between biological samples and selected minerals (including terrestrial, Moon- and Mars analogs) can be observed under space and Mars-like conditions. In this context, the Moon will be an additional platform for performing similar experiments with negligible magnetic shielding and higher solar and galactic irradiation compared to LEO. Using the Moon as an additional astrobiological exposure platform to complement ongoing astrobiological LEO investigations could thus enhance the chances of detecting organic traces of life on Mars. We present a lunar lander mission with two related objectives: a lunar lander equipped with Raman and PanCam instruments which can analyze the lunar surface and survey an astrobiological exposure platform. This dual use of testing mission technology together with geo- and astrobiological analyses will significantly increase the science return, and support the human preparation objectives. It will provide knowledge about the Moon's surface itself and, in addition, monitor the stability of life-markers, such as cells, cell components and pigments, in an extraterrestrial environment with much closer radiation properties to the surface of Mars. The combination of a Raman data base of these data together with data from LEO and space simulation experiments, will lead to further progress on the analysis and interpretation of data that we will obtain from future Moon and Mars exploration missions.
Photoaddressable alignment layers for fluorescent polymers in polarized electroluminescence devices
(2002)
BACKGROUND: Addiction is supposedly characterized by a shift from goal-directed to habitual decision making, thus facilitating automatic drug intake. The two-step task allows distinguishing between these mechanisms by computationally modeling goal-directed and habitual behavior as model-based and model-free control. In addicted patients, decision making may also strongly depend upon drug-associated expectations. Therefore, we investigated model-based versus model-free decision making and its neural correlates as well as alcohol expectancies in alcohol-dependent patients and healthy controls and assessed treatment outcome in patients. METHODS: Ninety detoxified, medication-free, alcohol-dependent patients and 96 age-and gender-matched control subjects underwent functional magnetic resonance imaging during the two-step task. Alcohol expectancies were measured with the Alcohol Expectancy Questionnaire. Over a follow-up period of 48 weeks, 37 patients remained abstinent and 53 patients relapsed as indicated by the Alcohol Timeline Followback method. RESULTS: Patients who relapsed displayed reduced medial prefrontal cortex activation during model-based decision making. Furthermore, high alcohol expectancies were associated with low model-based control in relapsers, while the opposite was observed in abstainers and healthy control subjects. However, reduced model-based control per se was not associated with subsequent relapse. CONCLUSIONS: These findings suggest that poor treatment outcome in alcohol dependence does not simply result from a shift from model-based to model-free control but is instead dependent on the interaction between high drug expectancies and low model-based decision making. Reduced model-based medial prefrontal cortex signatures in those who relapse point to a neural correlate of relapse risk. These observations suggest that therapeutic interventions should target subjective alcohol expectancies.
The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = -3.86, p < .001), but not in healthy controls (t = -0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t((30)) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.
In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.