The Manometer Task – A Task to Induce Steady Mental Load

With the Manometer Task (MNT) cognitive performance can be examined under conditions of constantly elevated mental load. An adaptive algorithm continuously adjusts the task difficulty in accordance to the previous individual performance. The task concept is described and the psychometric properties are reported for the recommended MNT-configuration with data of N = 2084 candidates. The results showed that the mean reaction times are unrelated to the performance quality of the respective individual. Although, the individual performance quality showed moderate stability across the three levels of task complexity (.32 < r < .34), we did not observe substantial correlations to other tests of cognitive performance. Gender differences were insignificant. Also, age correlations are small (r < .10). Several examples of different practical applications showed how the MNT can be applied to monitor individual performance under the influence of different external stressors

Surrogate-based Bayesian Comparison of Computationally Expensive Models: Application to Microbially Induced Calcite Precipitation

Geochemical processes in subsurface reservoirs affected by microbial activity change the material properties of porous media. This is a complex biogeochemical process in subsurface reservoirs that currently contains strong conceptual uncertainty. This means, several modeling approaches describing the biogeochemical process are plausible and modelers face the uncertainty of choosing the most appropriate one. Once observation data becomes available, a rigorous Bayesian model selection accompanied by a Bayesian model justifiability analysis could be employed to choose the most appropriate model, i.e. the one that describes the underlying physical processes best in the light of the available data. However, biogeochemical modeling is computationally very demanding because it conceptualizes different phases, biomass dynamics, geochemistry, precipitation and dissolution in porous media. Therefore, the Bayesian framework cannot be based directly on the full computational models as this would require too many expensive model evaluations. To circumvent this problem, we suggest performing both Bayesian model selection and justifiability analysis after constructing surrogates for the competing biogeochemical models. Here, we use the arbitrary polynomial chaos expansion. We account for the approximation error in the Bayesian analysis by introducing novel correction factors for the resulting model weights. Thereby, we extend the Bayesian justifiability analysis and assess model similarities for computationally expensive models. We demonstrate the method on a representative scenario for microbially induced calcite precipitation in a porous medium. Our extension of the justifiability analysis provides a suitable approach for the comparison of computationally demanding models and gives an insight on the necessary amount of data for a reliable model performance

Structured analysis of broader GMO impacts inspired by technology assessment to inform policy decisions.

If genetically modified organisms (GMOs) are approved in the EU for experimental release or marketing authorization (placing on the market), a risk assessment (RA) is carried out beforehand to determine whether this may be associated with negative effects on human health, nature or the environment. Applications are reviewed by the European Food Safety Authority (EFSA) and the national Competent Authorities of the Member States. However, the potential ramifications of the GMOs that are systematically addressed in the current RA context are limited. Broader consideration can include environmental and health aspects beyond the scope of the statutory RA, as well as societal, ethical and cultural impacts. These other levels of impact may be considered during the comitology process of authorisation, but how this is done is typically not made explicit in a systematic way. However, with the dynamic developments of new kinds of GMOs, these considerations as well as transparency regarding the role of broader considerations in political decision-making become more and more relevant. Against this backdrop, we identified the requirements and suggest the main elements for such a broader assessment. We use insights from the field of Technology Assessment (TA) to explore the requirements for operationalising a rapid but still systematic, transparent and broad case-by-case GMO assessment compatible with the existing legislative framework.publishedVersio

Memory Reduction via Delayed Simulation

We address a central (and classical) issue in the theory of infinite games: the reduction of the memory size that is needed to implement winning strategies in regular infinite games (i.e., controllers that ensure correct behavior against actions of the environment, when the specification is a regular omega-language). We propose an approach which attacks this problem before the construction of a strategy, by first reducing the game graph that is obtained from the specification. For the cases of specifications represented by "request-response"-requirements and general "fairness" conditions, we show that an exponential gain in the size of memory is possible.Comment: In Proceedings iWIGP 2011, arXiv:1102.374

Clinical, biochemical, and genetic spectrum of seven patients with NFU1 deficiency

Disorders of the mitochondrial energy metabolism are clinically and genetically heterogeneous. An increasingly recognized subgroup is caused by defective mitochondrial iron-sulfur (Fe-S) cluster biosynthesis, with defects in 13 genes being linked to human disease to date. Mutations in three of them, NFU1, BOLA3, and IBA57, affect the assembly of mitochondrial [4Fe-4S] proteins leading to an impairment of diverse mitochondrial metabolic pathways and ATP production. Patients with defects in these three genes present with lactic acidosis, hyperglycinemia, and reduced activities of respiratory chain complexes I and II, the four lipoic acid-dependent 2-oxoacid dehydrogenases and the glycine cleavage system (GCS). To date, five different NFU1 pathogenic variants have been reported in 15 patients from 12 families. We report on seven new patients from five families carrying compound heterozygous or homozygous pathogenic NFU1 mutations identified by candidate gene screening and exome sequencing. Six out of eight different disease alleles were novel and functional studies were performed to support the pathogenicity of five of them. Characteristic clinical features included fatal infantile encephalopathy and pulmonary hypertension leading to death within the first 6 months of life in six out of seven patients. Laboratory investigations revealed combined defects of pyruvate dehydrogenase complex (five out of five) and respiratory chain complexes I and II+III (four out of five) in skeletal muscle and/or cultured skin fibroblasts as well as increased lactate (five out of six) and glycine concentration (seven out of seven). Our study contributes to a better definition of the phenotypic spectrum associated with NFU1 mutations and to the diagnostic workup of future patients

Surrogate-based Bayesian comparison of computationally expensive models : application to microbially induced calcite precipitation

Geochemical processes in subsurface reservoirs affected by microbial activity change the material properties of porous media. This is a complex biogeochemical process in subsurface reservoirs that currently contains strong conceptual uncertainty. This means, several modeling approaches describing the biogeochemical process are plausible and modelers face the uncertainty of choosing the most appropriate one. The considered models differ in the underlying hypotheses about the process structure. Once observation data become available, a rigorous Bayesian model selection accompanied by a Bayesian model justifiability analysis could be employed to choose the most appropriate model, i.e. the one that describes the underlying physical processes best in the light of the available data. However, biogeochemical modeling is computationally very demanding because it conceptualizes different phases, biomass dynamics, geochemistry, precipitation and dissolution in porous media. Therefore, the Bayesian framework cannot be based directly on the full computational models as this would require too many expensive model evaluations. To circumvent this problem, we suggest to perform both Bayesian model selection and justifiability analysis after constructing surrogates for the competing biogeochemical models. Here, we will use the arbitrary polynomial chaos expansion. Considering that surrogate representations are only approximations of the analyzed original models, we account for the approximation error in the Bayesian analysis by introducing novel correction factors for the resulting model weights. Thereby, we extend the Bayesian model justifiability analysis and assess model similarities for computationally expensive models. We demonstrate the method on a representative scenario for microbially induced calcite precipitation in a porous medium. Our extension of the justifiability analysis provides a suitable approach for the comparison of computationally demanding models and gives an insight on the necessary amount of data for a reliable model performance.Deutsche ForschungsgemeinschaftProjekt DEA

Cyclotrons Operated for Nuclear Medicine and Radiopharmacy in the German Speaking D-A-CH Countries: An Update on Current Status and Trends

Background: Cyclotrons form a central infrastructure and are a resource of medical radionuclides for the development of new radiotracers as well as the production and supply of clinically established radiopharmaceuticals for patient care in nuclear medicine. Aim: To provide an updated overview of the number and characteristics of cyclotrons that are currently in use within radiopharmaceutical sciences and for the development of radiopharmaceuticals to be used for patient care in Nuclear Medicine in Germany (D), Austria (A) and Switzerland (CH). Methods: Publicly available information on the cyclotron infrastructure was (i) consolidated and updated, (ii) supplemented by selective desktop research and, last but not least, (iii) validated by members of the committee of the academic “Working Group Radiochemistry and Radiopharmacy” (AGRR), consisting of radiochemists and radiopharmacists of the D-A-CH countries and belonging to the German Society of Nuclear Medicine (DGN), as well as the Radiopharmaceuticals Committee of the DGN. Results: In total, 42 cyclotrons were identified that are currently being operated for medical radionuclide production for imaging and therapy in Nuclear Medicine clinics, 32 of them in Germany, 4 in Austria and 6 in Switzerland. Two thirds of the cyclotrons reported (67%) are operated by universities, university hospitals or research institutions close to a university hospital, less by/in cooperation with industrial partners (29%) or a non-academic clinic/ PET-center (5%). Most of the cyclotrons (88%) are running with up to 18 MeV proton beams, which is sufficient for the production of the currently most common cyclotron-based radionuclides for PET imaging. Discussion: The data presented provide an academically-updated overview of the medical cyclotrons operated for the production of radiopharmaceuticals and their use in Nuclear Medicine in the D-A-CH countries. In this context, we discuss current developments and trends with a view to the cyclotron infrastructure in these countries, with a specific focus on organizational aspects