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Abstract Variants within the monoamine oxidase A (MAO-A, MAOA) and tryptophan hydroxylase 2 (TPH2) genes, the main enzymes in cerebral serotonin (5-HT) turnover, affect risk for depression. Depressed cohorts show increased cerebral MAO-A in positron emission tomography (PET) studies. TPH2 polymorphisms might also influence brain MAO-A because availability of substrates (i.e. monoamine concentrations) were shown to affect MAO-A levels. We assessed the effect of MAOA (rs1137070, rs2064070, rs6323) and TPH2 (rs1386494, rs4570625) variants associated with risk for depression and related clinical phenomena on global MAO-A distribution volume (VT) using [11C]harmine PET in 51 participants (21 individuals with seasonal affective disorder (SAD) and 30 healthy individuals (HI)). Statistical analyses comprised general linear models with global MAO-A VT as dependent variable, genotype as independent variable and age, sex, group (individuals with SAD, HI) and season as covariates. rs1386494 genotype significantly affected global MAO-A VT after correction for age, group and sex (p

This article presents a flexible control interface based on low-cost hardware solutions for electric drives which classically come either with a proprietary hardware solution or a high-cost interface solution. The interface presented can be used to connect a standard PC with an electric drive to enable testing simulation and control applications. The control interface is developed based on the open-source Python scripting language and Arduino’s open-source and accessible hardware. The new interface communicates with the test stand through its I/O terminals via developed electronic amplifiers and creates a solid base for further development towards more extensive hardware in the loop simulations.

Abstract Background The NMDA receptor (NMDAR) plays a key role in the central nervous system, e.g., for synaptic transmission. While synaptic NMDARs are thought to have protective characteristics, activation of extrasynaptic NMDARs might trigger excitotoxic processes linked to neuropsychiatric disorders. Since extrasynaptic NMDARs are typically GluN2B-enriched, the subunit is an interesting target for drug development and treatment monitoring. Recently, the novel GluN2B-specific PET radioligand (R)-[11C]Me-NB1 was investigated in rodents and for the first time successfully translated to humans. To assess whether (R)-[11C]Me-NB1 is a valuable radioligand for (repeated) clinical applications, we evaluated its safety, biodistribution and dosimetry. Methods Four healthy subjects (two females, two males) underwent one whole-body PET/MR measurement lasting for more than 120 min. The GluN2B-specific radioligand (R)-[11C]Me-NB1 was administered simultaneously with the PET start. Subjects were measured in nine passes and six bed positions from head to mid-thigh. Regions of interest was anatomically defined for the brain, thyroid, lungs, heart wall, spleen, stomach contents, pancreas, liver, kidneys, bone marrow and urinary bladder contents, using both PET and MR images. Time-integrated activity coefficients were estimated to calculate organ equivalent dose coefficients and the effective dose coefficient. Additionally, standardized uptake values (SUV) were computed to visualize the biodistribution. Results Administration of the radioligand was safe without adverse events. The organs with the highest uptake were the urinary bladder, spleen and pancreas. Organ equivalent dose coefficients were higher in female in almost all organs, except for the urinary bladder of male. The effective dose coefficient was 6.0 µSv/MBq. Conclusion The GluN2B-specific radioligand (R)-[11C]Me-NB1 was well-tolerated without reported side effects. Effective dose was estimated to 1.8 mSv when using 300 MBq of presented radioligand. The critical organ was the urinary bladder. Due to the low effective dose coefficient of this radioligand, longitudinal studies for drug development and treatment monitoring of neuropsychiatric disorders including neurodegenerative diseases are possible. Trial registration Registered on 11th of June 2019 at https://www.basg.gv.at (EudraCT: 2018-002933-39).

The integration of heterogeneous and weakly linked log data poses a major challenge in many log-analytic applications. Knowledge graphs (KGs) can facilitate such integration by providing a versatile representation that can interlink objects of interest and enrich log events with background knowledge. Furthermore, graph-pattern based query languages, such as SPARQL, can support rich log analyses by leveraging semantic relationships between objects in heterogeneous log streams. Constructing, materializing, and maintaining centralized log knowledge graphs, however, poses significant challenges. To tackle this issue, we propose VloGraph—a distributed and virtualized alternative to centralized log knowledge graph construction. The proposed approach does not involve any a priori parsing, aggregation, and processing of log data, but dynamically constructs a virtual log KG from heterogeneous raw log sources across multiple hosts. To explore the feasibility of this approach, we developed a prototype and demonstrate its applicability to three scenarios. Furthermore, we evaluate the approach in various experimental settings with multiple heterogeneous log sources and machines; the encouraging results from this evaluation suggest that the approach can enable efficient graph-based ad-hoc log analyses in federated settings.

This paper describes Open-Instance Power System Library (OpenIPSL) version 2.0.0 and its most recent enhancements. This new version brings upgrades that include more robust models that are better documented, and example systems that illustrate certain functionalities to users. Repository and library documentations have been enhanced and expanded, and the library is now released under a new license. Changes are meant to foster user and developer communities, while providing more attractive frameworks for collaborative work to be carried out with the library.

Abstract Antidepressant doses of ketamine rapidly facilitate synaptic plasticity and modify neuronal function within prefrontal and hippocampal circuits. However, most studies have demonstrated these effects in animal models and translational studies in humans are scarce. A recent animal study showed that ketamine restored dendritic spines in the hippocampal CA1 region within 1 h of administration. To translate these results to humans, this randomized, double-blind, placebo-controlled, crossover magnetic resonance imaging (MRI) study assessed ketamine’s rapid neuroplastic effects on hippocampal subfield measurements in healthy volunteers. S-Ketamine vs. placebo data were analyzed, and data were also grouped by brain-derived neurotrophic factor (BDNF) genotype. Linear mixed models showed that overall hippocampal subfield volumes were significantly larger (p = 0.009) post ketamine than post placebo (LS means difference=0.008, standard error=0.003). Post-hoc tests did not attribute effects to specific subfields (all p > 0.05). Trend-wise volumetric increases were observed within the left hippocampal CA1 region (p = 0.076), and trend-wise volumetric reductions were obtained in the right hippocampal—amygdaloid transition region (HATA) (p = 0.067). Neither genotype nor a genotype–drug interaction significantly affected the results (all p > 0.7). The study provides evidence that ketamine has short-term effects on hippocampal subfield volumes in humans. The results translate previous findings from animal models of depression showing that ketamine has pro-neuroplastic effects on hippocampal structures and underscore the importance of the hippocampus as a key region in ketamine’s mechanism of action.

An essential core function of one's cognitive flexibility is the use of acquired knowledge and skills to adapt to ongoing environmental changes. Animal models have highlighted the influence serotonin has on neuroplasticity. These effects have been predominantly demonstrated during emotional relearning which is theorized as a possible model for depression. However, translation of these mechanisms is in its infancy. To this end, we assessed changes in effective connectivity at rest and during associative learning as a proxy of neuroplastic changes in healthy volunteers. 76 participants underwent 6 weeks of emotional or non-emotional (re)learning (face-matching or Chinese character–German noun matching). During relearning participants either self-administered 10 mg/day of the selective serotonin reuptake inhibitor (SSRI) escitalopram or placebo in a double-blind design. Associative learning tasks, resting-state and structural images were recorded before and after both learning phases (day 1, 21 and 42). Escitalopram intake modulated relearning changes in a network encompassing the right insula, anterior cingulate cortex and right angular gyrus. Here, the process of relearning during SSRI intake showed a greater decrease in effective connectivity from the right insula to both the anterior cingulate cortex and right angular gyrus, with increases in the opposite direction when compared to placebo. In contrast, intrinsic connections and those at resting-state were only marginally affected by escitalopram. Further investigation of gray matter volume changes in these functionally active regions revealed no significant SSRI-induced structural changes. These findings indicate that the right insula plays a central role in the process of relearning and SSRIs further potentiate this effect. In sum, we demonstrated that SSRIs amplify learning-induced effective connections rather than affecting the intrinsic task connectivity or that of resting-state.

Abstract Background Measures to reduce the spread of the SARS-CoV-2 virus have an impact on the mental health of the general population. Drug prescription rates can be used as a surrogate marker to estimate help seeking and health parameters of a population. The aim of this study was to compare psychopharmacologic drug prescriptions in Austria from the start of the pandemic in 2020 over time and with the previous year and to investigate the impact of the COVID-19 lockdowns in 2020. Methods Data from the three largest public health insurances in Austria, covering over 98% of the general population, were analyzed. A total of 1,365,294 patients with a prescription of a psychopharmacologic drug in the months March to December in 2019 and 2020 were selected. Results There was no significant change in prescribed defined daily doses (DDDs) during the lockdowns. However, there was a stockpiling effect before and at the beginning of lockdown 1. The number of new patients initiating psychopharmacologic treatment was significantly reduced during lockdown 1 but not during lockdown 2. Conclusions The first COVID-19 lockdown in 2020 functioned as a barrier for new psychiatric patients seeking help, whereas the patients with ongoing treatments did not have significant problems. These results have to be taken into account for future planning, but follow-up studies are needed, as our results could be indicative of a change in the effect of the protective measures on the utilization of the healthcare system over time.

Abstract Background Alcohol is one of the leading exogenous causes for adverse health consequences in Europe. The aim of the present study was to examine the pattern of alcohol consumption in Austrian physicians. Methods A telephone survey was conducted in 400 office-based physicians in Austria. Our questionnaire included the four questions of the CAGE questionnaire and questions to assess alcohol consumption on the previous day. Results 131 participants (32.8%) completed the interview. 3.8% of the subjects had a CAGE score of 2 or higher indicating a problem with alcohol, but this rate was not statistically different from numbers reported for the general population (4.1%). 46.6% of our subjects had drunken alcohol on the previous day. Compared to the general population, the rate of having drunk alcohol yesterday was higher in both gender of our sample, but the amount of alcohol drunk was significantly lower. Doctors in rural areas had drunken alcohol more frequently and in greater quantities on the previous day than those in urban areas. There was a positive correlation between age and the amount of drinking on the previous day, and between age and CAGE scores. Furthermore, subjects who had consumed alcohol yesterday obtained higher scores on the CAGE. Conclusions Our findings indicate that the rate of Austrian physicians with problematic alcohol consumption is similar to the general population. Physicians in rural areas and older doctors might be of higher risk for alcohol abuse.

Objective: The aim of this repeated cross-sectional study was to compare patients from a psychiatric intensive care unit (PICU) over ≫30 years regarding their diagnostic and therapeutic characteristics. Method: Three samples including 100 consecutive inpatients each from the Viennese PICU were submitted to a chart review: sample no. 1 from the years 1985/86, no. 2 from 1995/96 and no. 3 from 2007/08. Results: Changes in referral modes were associated with a decrease of patients with substance induced disorders and an increase of patients with affective disorders over time. The rate of admissions after accidents and suicides was stable. The use of cranial MRI increased, while intravenous psychopharmacotherapy and parenteral nutrition decreased. Involuntary admission occurred in 43% and in 37% of patients physical restraints were necessary. We saw a shift from tricyclic antidepressants to SSRIs and SNRIs from sample 1 to 3. Likewise, we observed the emergence of atypical antipsychotics and a reduction of use of typical neuroleptics mainly from sample 2 to 3. The percentage of patients receiving benzodiazepines increased over time, while the mean dosage of benzodiazepines decreased. 7% of patients received electroconvulsive therapy. Conclusions: The changes over time in our samples reflect the medical progress made during the last decades. Future studies should focus on evaluation of efficacy of psychiatric intensive care using standardized measurements. Keywords: Mental health services, Intensive care, History, Psychopharmacology, Antidepressants, Antipsychotics

Abstract Numerous studies demonstrate ketamine’s influence on resting-state functional connectivity (rsFC). Seed-based and static rsFC estimation methods may oversimplify FC. These limitations can be addressed with whole-brain, dynamic rsFC estimation methods. We assessed data from 27 healthy subjects who underwent two 3 T resting-state fMRI scans, once under subanesthetic, intravenous esketamine and once under placebo, in a randomized, cross-over manner. We aimed to isolate only highly robust effects of esketamine on dynamic rsFC by using eight complementary methodologies derived from two dynamic rsFC estimation methods, two functionally defined atlases and two statistical measures. All combinations revealed a negative influence of esketamine on dynamic rsFC within the left visual network and inter-hemispherically between visual networks (p

Background: Valproic acid (VPA) has been increasingly shown to trigger hyperammonemic encephalopathies in patients suffering from urea cycle defects and in those receiving polypharmacy. Methods: We report on two cases of psychiatric inpatients with regular VPA intake who showed severe cognitive impairment due to non-cirrhotic hyperammonaemia without VPA overdosing. Results: In the first case, OTC deficiency appeared to be the underlying cause of a comatose state in a middle-aged bipolar female patient. Besides hyperammonemia, we identified increased plasma levels of glutamine and alanine, decreased plasma levels of arginine and urea, as well as increased urinary levels of orotate. In the second case, we observed severe cognitive impairment in a younger male patient with a current psychotic episode with predominant affective symptoms who we treated with polypharmacy including VPA and topiramate. Limitations: As this case series focused on individual patients, the results should be interpreted with caution and cannot be generalized. Conclusions: In patients receiving VPA, considering urea cycle deficiencies and potential drug interactions seems crucial for avoiding potential life-threatening symptoms.

The diagnosis of parkinsonian syndromes in patients with severe depression may be challenging due to overlapping clinical phenomena, especially regarding psychomotor and affective symptoms. [123I]FP-CIT-SPECT is a useful method to detect degenerative parkinsonian disorders. However, some drugs may influence the tracer binding and thus alter the result. We present a case of 56-year-old female inpatient with difficult-to-treat late-onset depression. Since the current major depressive episode (MDE) was accompanied by psychotic features including delusions and hallucinations as well as hypokinesia, stooped posture and hypomimia, underlying degenerative parkinsonism was suspected. The pathologic [123I]FP-CIT-SPECT scan under ongoing antidepressant therapy with bupropion 300 mg/die (serum level of bupropion 43 ng/ml and hydroxybupropion 2,332 ng/ml) showed reduced [123I]FP-CIT binding throughout the striatum. The scan normalized upon a wash-out phase of four half-time periods (serum level of bupropion was 0.4 ng/ml and for hydroxybupropion 80.5 ng/ml). Our report should serve as a cautionary note for use of [123I]FP-CIT in depressed patients, particularly in those treated with drugs interfering with the dopamine transporter. Furthermore, our case argues for a need of consultation of a movement disorder specialist prior to dopamine transporter imaging.

One of the most important issues in scenario-based software architecture evaluation is the development of scenarios for characterizing a desired set of quality attributes by holding meetings of stakeholders. As such meetings are costly to arrange, studying the effectiveness of such meetings is an important research question. In this paper, we report on the findings from a software architecture evaluation empirical study aimed at investigating the effectiveness of scenario development meetings in terms of the quantity of gained and lost scenarios during the evaluation process. The findings from the experiment data analysis raise the question about the effectiveness of holding meetings for developing scenarios as more existing scenarios were lost than new scenarios were gained as a result of these meetings.

Due to the increasing use of renewable energy sources, and to counter the effects of fossil fuels, renewable dispatchable hydro power can be used for balancing load and generation from intermittent sources (solar and wind). During higher percentage change in load acceptance or rejection in the intermittent grid, the operations of surge tanks are crucial in terms of water mass oscillation and water hammer pressure, and to avoid wear and tear in actuators and other equipment, such as hydro turbines. Surge tanks are broadly classified as open types, with access to open air, and closed types, with a closed volume of pressurized air. Closed surge tanks are considered to have a more flexible operation in terms of suppressing water mass oscillation and water hammer pressure. In this paper, a mechanistic model of an air cushion surge tank (ACST) for hydro power plants is developed based on the ordinary differential equations (ODEs) for mass and momentum balances. The developed mechanistic model of the ACST is a feature extension to an existing open-source hydro power library—OpenHPL. The developed model is validated with experimental data from the Torpa hydro power plant (HPP) in Norway. Results show that the air friction inside the ACST is negligible as compared to the water friction. The results also indicate that a hydro power plant with an ACST is a potential candidate as a flexible hydro power in an interconnected power system grid supplied with intermittent energy sources. Conclusions are drawn based on the simulation results from hydraulic performance of the ACST.

Abstract Background Seasonal affective disorder (SAD) is a seasonally recurrent type of major depression that has detrimental effects on patients’ lives during winter. Little is known about how it affects patients during summer and about patients’ and physicians’ perspectives on preventive SAD treatment. The aim of our study was to explore how SAD patients experience summers, what type of preventive treatment patients implement, which preventive treatment methods, if any, physicians recommend, and what factors facilitate or hinder implementation/recommendation of SAD prevention. Methods We conducted 15 semi-structured interviews, ten with adult patients with a history of SAD and five with physicians. Transcripts were analyzed by two researchers using an inductive thematic analysis approach. Results One group of patients was able to enjoy summer and ignore thoughts of the upcoming winter. The other group feared the impending depressive episode in winter, and this fear negatively impacted these patients’ well-being during the summer. Preventive treatment was a relevant issue for all patients, and all but one person implemented SAD prevention during summer. We identified six factors that influenced patient use of preventive treatment of SAD. Four factors occur on an individual level (knowledge about disease and preventive treatment options, experience with treatment in acute phase, acceptability of intervention, willingness to take responsibility for oneself), one on an interpersonal level (social and work environment), and one on a structural level (healthcare system). All psychiatrists recommended some kind of preventive intervention, most commonly, lifestyle changes. Four factors influenced psychiatrists in recommending prevention of SAD (patient expectations, disease history and stability, risk/benefit ratio, lack of evidence). Conclusions Success in the implementation of SAD prevention does not solely depend on the willingness of the patients, but is also influenced by external factors. Raising awareness of SAD among general practitioners and low-level access to mental-health support could help patients find appropriate help sooner. To better guide the optimal treatment choice, comparative effectiveness research on treatments to prevent a new onset in patients with a history of SAD and clinical practice guidelines on SAD are needed.

Abstract Background Seasonal changes and climatic factors like ambient temperature, sunlight duration and rainfall can influence suicidal behavior. Methods This study analyses the relationship between seasonal changes and climatic variations and suicide attempts in 2131 young patients in Istanbul, Turkey. Results In our study sample, there was an association between suicide attempts in youths and seasonal changes, as suicide attempts occurred most frequently during summer in females as well as in males. Furthermore, there was a positive correlation between the mean temperature over the past 10 days and temperature at the index day and suicide attempts in females. After seasonality effects were mathematically removed, the mean temperature 10 days before a suicide attempt remained significant in males only, indicating a possible short-term influence of temperature on suicide attempts. Conclusions This study shows an association between suicide attempts of young people and climatic changes, in particular temperature changes as well as seasonal changes. Therefore, the influence of seasonal changes and climatic factors on young suicide attempters should get more attention in research to understand the biopsychosocial mechanisms playing a role in suicide attempts of young people. As suicide attempts most frequently occur in young people, further research is of considerable clinical importance.

In a microgrid connected with both intermittent and dispatchable sources, intermittency caused by sources such as solar and wind power plants can be balanced by dispatching hydro power into the grid. Both intermittent generation and consumption are stochastic in nature, not known perfectly, and require future prediction. The stochastic generation and consumption will cause the grid frequency to drift away from a required range. To improve performance, operation should be optimized over some horizon, with the added problem that intermittent power varies randomly into the future. Optimal management of dynamic system over a future horizon with disturbances is often posed as a Model Predictive Control (MPC) problem. In this paper, we have employed an MPC scheme for generating a hydro-turbine valve signal for dispatching necessary hydro power to the intermittent grid and maintaining grid frequency. Parameter sensitivity analysis shows that grid frequency is mostly sensitive to the turbine valve signal. We have found that controller discretization time, grid frequency, and power injection into the grid are interrelated, and play an important role in maintaining the grid frequency within the thresholds. Results also indicate that the fluctuations in grid frequency are insignificant on the turbine valve position during power injection into the grid.

[Context] Models play an important role in Software and Systems Engineering processes. Reviews are well-established methods for model quality assurance that support early and efficient defect detection. However, traditional document-based review processes have limitations with respect to the number of experts, resources, and the document size that can be applied. [Objective] In this paper, we introduce a distributed and scalable review process for model quality assurance to (a) improve defect detection effectiveness and (b) to increase review artifact coverage. [Method] We introduce the novel concept of Expected Model Elements (EMEs) as a key concept for defect detection. EMEs can be used to drive the review process. We adapt a best-practice review process to distinguish (a) between the identification of EMEs in the reference document and (b) the use of EMEs to detect defects in the model. We design and evaluate the adapted review process with a crowdsourcing tool in a feasibility study. [Results] The study results show the feasibility of the adapted review process. Further, the study showed that inspectors using the adapted review process achieved results for defect detection effectiveness, which are comparable to the performance of inspectors using a traditional inspection process, and better defect detection efficiency. Moreover, from a practical perspective the adapted review process can be used to complement inspection efforts conducted using the traditional inspection process, enhancing the overall defect detection effectiveness. [Conclusions] Although the study shows promising results of the novel process, future investigations should consider larger and more diverse review artifacts and the effect of using limited and different scopes of artifact coverage for individual inspectors.

Master studies in process automation started in 1989 at what soon became Telemark University College, and the 20 year anniversary marks the start of our own PhD degree in Process, Energy and Automation Engineering. The paper gives an overview of research activities related to control engineering at Department of Electrical Engineering, Information Technology and Cybernetics.