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This study examines the institutionalization of information technologies for policy formulation by investigating the case of eNAP. The digital tool was introduced in the spring of 2018 with the aim of supporting and improving sustainability impact assessments (SIAs) within the German Federal Government. Applying a neo-institutional perspective, this study shows how a tool like eNAP is embedded into prevailing regulative, normative, and cultural–cognitive structures. Findings from 10 semi-structured interviews indicate that the application of eNAP varies according to intra-ministerial coordination practices and portfolio-specific information-processing schemata. Overall, the tool serves to translate the abstract regulation to conduct an SIA, as well as to translate the vague norm of “sustainability” into a concrete assessment requirement, thereby helping increase policy officials’ awareness of sustainability goals. However, consistent with previous studies, great importance is not attached to SIAs in policy formulation, and prevailing norms and routines make the implementation of eNAP to increase the use of evidence or in-depth considerations of policy alternatives and their consequences unlikely.
While previous research underscores the role of leaders in stimulating employee voice behaviour, comparatively little is known about what affects leaders' support for such constructive but potentially threatening employee behaviours. We introduce leader member exchange quality (LMX) as a central predictor of leaders' support for employees' ideas for constructive change. Apart from a general benefit of high LMX for leaders' idea support, we propose that high LMX is particularly critical to leaders' idea support if the idea voiced by an employee constitutes a power threat to the leader. We investigate leaders' attribution of prosocial and egoistic employee intentions as mediators of these effects. Hypotheses were tested in a quasi-experimental vignette study (N = 160), in which leaders evaluated a simulated employee idea, and a field study (N = 133), in which leaders evaluated an idea that had been voiced to them at work. Results show an indirect effect of LMX on leaders' idea support via attributed prosocial intentions but not via attributed egoistic intentions, and a buffering effect of high LMX on the negative effect of power threat on leaders' idea support. Results differed across studies with regard to the main effect of LMX on idea support.
In recent years, many efforts have been made to apply image processing techniques for plant leaf identification. However, categorizing leaf images at the cultivar/variety level, because of the very low inter-class variability, is still a challenging task. In this research, we propose an automatic discriminative method based on convolutional neural networks (CNNs) for classifying 12 different cultivars of common beans that belong to three various species. We show that employing advanced loss functions, such as Additive Angular Margin Loss and Large Margin Cosine Loss, instead of the standard softmax loss function for the classification can yield better discrimination between classes and thereby mitigate the problem of low inter-class variability. The method was evaluated by classifying species (level I), cultivars from the same species (level II), and cultivars from different species (level III), based on images from the leaf foreside and backside. The results indicate that the performance of the classification algorithm on the leaf backside image dataset is superior. The maximum mean classification accuracies of 95.86, 91.37 and 86.87% were obtained at the levels I, II and III, respectively. The proposed method outperforms the previous relevant works and provides a reliable approach for plant cultivars identification.
Electronic databases of landslides seldom include the triggering mechanisms, rendering these inventories unusable for landslide hazard modeling. We present a method for classifying the triggering mechanisms of landslides in existing inventories, thus, allowing these inventories to aid in landslide hazard modeling corresponding to the correct event chain. Our method uses various geometric characteristics of landslides as the feature space for the machine-learning classifier random forest, resulting in accurate and robust classifications of landslide triggers. We applied the method to six landslide inventories spread over the Japanese archipelago in several different tests and training configurations to demonstrate the effectiveness of our approach. We achieved mean accuracy ranging from 67% to 92%. We also provide an illustrative example of a real-world usage scenario for our method using an additional inventory with unknown ground truth. Furthermore, our feature importance analysis indicates that landslides having identical trigger mechanisms exhibit similar geometric properties.
While patients are known to respond differently to drug therapies, current clinical practice often still follows a standardized dosage regimen for all patients. For drugs with a narrow range of both effective and safe concentrations, this approach may lead to a high incidence of adverse events or subtherapeutic dosing in the presence of high patient variability. Model-informedprecision dosing (MIPD) is a quantitative approach towards dose individualization based on mathematical modeling of dose-response relationships integrating therapeutic drug/biomarker monitoring (TDM) data. MIPD may considerably improve the efficacy and safety of many drug therapies. Current MIPD approaches, however, rely either on pre-calculated dosing tables or on simple point predictions of the therapy outcome. These
approaches lack a quantification of uncertainties and the ability to account for effects that are delayed. In addition, the underlying models are not improved while applied to patient data. Therefore, current approaches are not well suited for informed clinical decision-making based on a differentiated understanding of the individually predicted therapy outcome.
The objective of this thesis is to develop mathematical approaches for MIPD, which (i) provide efficient fully Bayesian forecasting of the individual therapy outcome including associated uncertainties, (ii) integrate Markov decision processes via reinforcement learning (RL) for a comprehensive decision framework for dose individualization, (iii) allow for continuous learning across patients and hospitals. Cytotoxic anticancer chemotherapy with its major dose-limiting toxicity, neutropenia, serves as a therapeutically relevant application example.
For more comprehensive therapy forecasting, we apply Bayesian data assimilation (DA) approaches, integrating patient-specific TDM data into mathematical models of chemotherapy-induced neutropenia that build on prior population analyses. The value of uncertainty quantification is demonstrated as it allows reliable computation of the patient-specific probabilities of relevant clinical quantities, e.g., the neutropenia grade. In view of novel home monitoring devices that increase the amount of TDM data available, the data processing of
sequential DA methods proves to be more efficient and facilitates handling of the variability between dosing events.
By transferring concepts from DA and RL we develop novel approaches for MIPD. While DA-guided dosing integrates individualized uncertainties into dose selection, RL-guided dosing provides a framework to consider delayed effects of dose selections. The combined
DA-RL approach takes into account both aspects simultaneously and thus represents a holistic approach towards MIPD. Additionally, we show that RL can be used to gain insights into important patient characteristics for dose selection. The novel dosing strategies substantially reduce the occurrence of both subtherapeutic and life-threatening neutropenia grades in a simulation study based on a recent clinical study (CEPAC-TDM trial) compared to currently used MIPD approaches.
If MIPD is to be implemented in routine clinical practice, a certain model bias with respect to the underlying model is inevitable, as the models are typically based on data from comparably small clinical trials that reflect only to a limited extent the diversity in real-world patient populations. We propose a sequential hierarchical Bayesian inference framework that enables continuous cross-patient learning to learn the underlying model parameters of the target patient population. It is important to note that the approach only requires summary information of the individual patient data to update the model. This separation of the individual inference from population inference enables implementation across different centers of care.
The proposed approaches substantially improve current MIPD approaches, taking into account new trends in health care and aspects of practical applicability. They enable progress towards more informed clinical decision-making, ultimately increasing patient benefits beyond the current practice.
Long- and short-term monitoring of a dam in response to seasonal changes and ground motion loading
(2021)
An experimental multi-parameter structural monitoring system has been installed on the Kurpsai dam, western Kyrgyz Republic. This system consists of equipment for seismic and strain measurements for making longer- (days, weeks, months) and shorter- (minutes, hours) term observations, dealing with, for example seasonal (longer) effects or the response of the dam to ground motion from noise or seismic events. Fibre-optic strain sensors allow the seasonal and daily opening and closing of the spaces between the dam's segments to be tracked. For the seismic data, both amplitude (in terms of using differences in amplitudes in the Fourier spectra for mapping the modes of vibration of the dam) and their time-frequency distribution for a set of small to moderate seismic events are investigated and the corresponding phase variabilities (in terms of lagged coherency) are evaluated. Even for moderate levels of seismic-induced ground motion, some influence on the structural response can be detected, which then sees the dam quickly return to its original state. A seasonal component was identified in the strain measurements, while levels of noise arising from the operation of the dam's generators and associated water flow have been provisionally identified.
Lost in Germania
(2021)
Tacitus’ Germania is notable for its absences: lacking a preface and programmatic statements, and being the only ethnographic monograph to have survived from Greco-Roman antiquity, readers have often leapt to fill in its perceived blanks. This chapter aims at redressing the effects of overdetermined readings by interpreting the text’s absences as significant in their own right.
The olfactomotor system is especially investigated by examining the sniffing in reaction to olfactory stimuli. The motor output of respiratory-independent muscles was seldomly considered regarding possible influences of smells. The Adaptive Force (AF) characterizes the capability of the neuromuscular system to adapt to external forces in a holding manner and was suggested to be more vulnerable to possible interfering stimuli due to the underlying complex control processes. The aim of this pilot study was to measure the effects of olfactory inputs on the AF of the hip and elbow flexors, respectively. The AF of 10 subjects was examined manually by experienced testers while smelling at sniffing sticks with neutral, pleasant or disgusting odours. The reaction force and the limb position were recorded by a handheld device. The results show, inter alia, a significantly lower maximal isometric AF and a significantly higher AF at the onset of oscillations by perceiving disgusting odours compared to pleasant or neutral odours (p < 0.001). The adaptive holding capacity seems to reflect the functionality of the neuromuscular control, which can be impaired by disgusting olfactory inputs. An undisturbed functioning neuromuscular system appears to be characterized by a proper length tension control and by an earlier onset of mutual oscillations during an external force increase. This highlights the strong connection of olfaction and motor control also regarding respiratory-independent muscles.
The regulation of oxygen and blood supply during isometric muscle actions is still unclear. Recently, two behavioral types of oxygen saturation (SvO(2)) and relative hemoglobin amount (rHb) in venous microvessels were described during a fatiguing holding isometric muscle action (HIMA) (type I: nearly parallel behavior of SvO(2) and rHb; type II: partly inverse behavior). The study aimed to ascertain an explanation of these two regulative behaviors. Twelve subjects performed one fatiguing HIMA trial with each arm by weight holding at 60% of the maximal voluntary isometric contraction (MVIC) in a 90 & DEG; elbow flexion. Six subjects additionally executed one fatiguing PIMA trial by pulling on an immovable resistance with 60% of the MVIC with each side and same position. Both regulative types mentioned were found during HIMA (I: n = 7, II: n = 17) and PIMA (I: n = 3, II: n = 9). During the fatiguing measurements, rHb decreased initially and started to increase in type II at an average SvO(2)-level of 58.75 & PLUSMN; 2.14%. In type I, SvO(2) never reached that specific value during loading. This might indicate the existence of a threshold around 59% which seems to trigger the increase in rHb and could explain the two behavioral types. An approach is discussed to meet the apparent incompatibility of an increased capillary blood filling (rHb) despite high intramuscular pressures which were found by other research groups during isometric muscle actions.
The link between emotions and motor control has been discussed for years. The measurement of the Adaptive Force (AF) provides the possibility to get insights into the adaptive control of the neuromuscular system in reaction to external forces. It was hypothesized that the holding isometric AF is especially vulnerable to disturbing inputs. Here, the behavior of the AF under the influence of positive (tasty) vs. negative (disgusting) food imaginations was investigated. The AF was examined in n = 12 cases using an objectified manual muscle test of the hip flexors, elbow flexors or pectoralis major muscle, performed by one of two experienced testers while the participants imagined their most tasty or most disgusting food. The reaction force and the limb position were measured by a handheld device. While the slope of force rises and the maximal AF did not differ significantly between tasty and disgusting imaginations (p > 0.05), the maximal isometric AF was significantly lower and the AF at the onset of oscillations was significantly higher under disgusting vs. tasty imaginations (both p = 0.001). A proper length tension control of muscles seems to be a crucial functional parameter of the neuromuscular system which can be impaired instantaneously by emotionally related negative imaginations. This might be a potential approach to evaluate somatic reactions to emotions.
Klinische Analyse der physiologischen und pathologischen Sehnenadaptation an sportliche Belastung
(2021)
Nonparametric goodness-of-fit testing for parametric covariate models in pharmacometric analyses
(2021)
The characterization of covariate effects on model parameters is a crucial step during pharmacokinetic/pharmacodynamic analyses. Although covariate selection criteria have been studied extensively, the choice of the functional relationship between covariates and parameters, however, has received much less attention. Often, a simple particular class of covariate-to-parameter relationships (linear, exponential, etc.) is chosen ad hoc or based on domain knowledge, and a statistical evaluation is limited to the comparison of a small number of such classes. Goodness-of-fit testing against a nonparametric alternative provides a more rigorous approach to covariate model evaluation, but no such test has been proposed so far. In this manuscript, we derive and evaluate nonparametric goodness-of-fit tests for parametric covariate models, the null hypothesis, against a kernelized Tikhonov regularized alternative, transferring concepts from statistical learning to the pharmacological setting. The approach is evaluated in a simulation study on the estimation of the age-dependent maturation effect on the clearance of a monoclonal antibody. Scenarios of varying data sparsity and residual error are considered. The goodness-of-fit test correctly identified misspecified parametric models with high power for relevant scenarios. The case study provides proof-of-concept of the feasibility of the proposed approach, which is envisioned to be beneficial for applications that lack well-founded covariate models.
Hintergrund. Personen, die mit der chronischen Erkrankung HIV leben (PWH), müssen ihr Leben lang die sog. antiretrovirale Therapie (ART) einnehmen, um einen Ausbruch der Erkrankung in das Vollbild AIDS (Akquiriertes Immun-Defizienz-Syndrom) zu vermeiden. Gleichzeitig ist die ART und HIV selbst assoziiert mit dem Auftreten zusätzlicher Erkrankungen (Komorbiditäten) kardiovaskulärer oder psychologischer Natur. Die Prävalenz von Komorbiditäten und schlechter Lebensqualität ist im Vergleich zu HIV-negativen Personen deutlich höher.
Methoden. Es wurden zwei Metaanalysen zu sportlicher Betätigung, PWH und (1) kardiovaskulären und (2) psychologischen Parametern sowie eine Querschnittsstudie (HIBES-Studie, HIV-Begleiterkrankungen und Sport) durchgeführt. Für die Auswertung der metaanalytischen Daten wurde der Review Manager 5.3, für die Auswertung der Daten der HIBES-Studie das Analyseprogramm „R“ verwendet. In den Metaanalysen wurden, neben den Hauptanalysen verschiedener Parameter, erstmals spezifische Subgruppenanalysen durchgeführt. Die HIBES-Studie untersuchte Unterschiede zwischen kumulativen (2-3 verschiedenen Sportarten pro Woche) und einfachen (eine Sportart pro Woche) Freizeitsport und analysiert die Zusammenhänge von Parametern des Freizeitsports (Trainingshäufigkeit, -Minuten und –Intensität), Komorbiditäten und der Lebensqualität.
Ergebnisse. Ausdauer- und Krafttraining haben einen mittel-starken bis starken positiven Effekt auf die maximale Sauerstoffaufnahme (SMD= 0.66, p< .00001), den 6-Minuten-Walk-Test (6MWT) (SMD= 0.59, p= .02), die maximale Watt Zahl (SMD= 0.80, p= .009). Kein Effekt wurde bei der maximalen Herzfrequenz und dem systolischen sowie diastolischen Blutdruck gefunden. Subgruppenanalysen zu ≥3 Einheiten/Woche, ≥150 Min./Woche ergaben hohe Effektstärken in der maximalen Watt Zahl und 6MWT. Ausdauer- und Krafttraining zusammen mit Yoga haben einen starken Effekt auf Symptome der Depression (SMD= -0.84, p= .02) und Angststörungen (SMD= -1.23, p= .04). Die Subanalyse der Depression zu professioneller Supervision und sportlicher Betätigung wiesen einen sehr starken Effekt (SMD= -1.40, p= .03). Die HIBES-Studie wies ein sehr differenziertes Bild im Sportverhalten von PWH in Deutschland auf. 49% der Teilnehmer übten mehr als eine Sportart pro Woche aus. Es wurden keine Unterschiede zwischen kumuliertem (CTE) und einfachem Sport (STE) in der Lebensqualität gefunden. Die Freizeitsportparameter (Häufigkeiten/Woche, Minuten/Woche, Intensität/Woche) waren in der CTE-Gruppe deutlich höher als in der STE-Gruppe. Trainingsminuten und die -Intensität zeigten beim Vorhandensein einer Komorbidität einen großen Zusammenhang mit der Lebensqualität. Die Minuten und die Intensität des durchgeführten Sportes zeigten einen prädiktiven Zusammenhang mit der Lebensqualität.
Konklusion: Sportliche Betätigung verbessert die maximale Sauerstoffaufnahme und Symptome der Depression und Angststörungen. Die Aussagekraft der Subanalysen ist aufgrund der geringen Studienzahl, vorsichtig zu interpretieren. Erhöhte Trainingsparameter finden sich eher bei PWH, die mehr als eine Sportart pro Woche treiben. Daher kann kumulierter Sport als mediierender Faktor zur Steigerung der Lebensqualität interpretiert werden; zumindest bei PWH mit einer psychologischen Komorbidität.
Background
Recent research emphasized the role of inflammatory processes in the pathophysiology of depression. Theories hypothesizes that life events (LE) can affect the immune system and trigger depressive symptoms. LE are also considered as one of the best predictors for the onset and course of depressive disorders.
Methods
Observational study across three treatment settings: n=208 depressive patients (75.5%f, M 46.6 y) were examined on depression (BDI-II), life events (ILE) and inflammatory markers (IL-6, CRP, fibrinogen, ICAM-1, TNF-alpha, E-selectin) at baseline (t0), 5-week(t1) and 5-month(t2) follow-up. Effects and interactions were analyzed with regression models.
Results
LE were associated with depressive symptoms at t0 (beta=.209; p=.002) and both follow-ups. Except for CRP, which was linked to depression symptoms at t2 (betai=-.190; p=.032), there were no effects of inflammatory markers on depressive symptoms. At t1, an interaction between CRP and LE in total (beta=-.249; p=.041) was found as well as for LE in the past five years (beta=-.122; p=.027). Similar interactions were found between cumulative LE and ICAM-1 (beta=-.197; p=.003) and IL-6 (beta=-.425; p=.001).
Conclusion
The cumulative burden of LE effects symptoms and treatment outcome in depressive patients. There is some evidence that inflammatory marker may have long-term effects on treatment outcome as they seem to weaken the determining relation between LE and depression.
Background
Depression is one of the key factors contributing to difficulties in one’s ability to work, and serves as one of the major reasons why employees apply for psychotherapy and receive insurance subsidization of treatments. Hence, an increasing and growing number of studies rely on workability assessment scales as their primary outcome measure. The Work and Social Assessment Scale (WSAS) has been documented as one of the most psychometrically reliable and valid tools especially developed to assess workability and social functioning in patients with mental health problems. Yet, the application of the WSAS in Germany has been limited due to the paucity of a valid questionnaire in the German language. The objective of the present study was to translate the WSAS, as a brief and easy administrable tool into German and test its psychometric properties in a sample of adults with depression.
Methods
Two hundred seventy-seven patients (M = 48.3 years, SD = 11.1) with mild to moderately severe depression were recruited. A multistep translation from English into the German language was performed and the factorial validity, criterion validity, convergent validity, discriminant validity, internal consistency, and floor and ceiling effects were examined.
Results
The confirmatory factor analysis results confirmed the one-factor structure of the WSAS. Significant correlations with the WHODAS 2–0 questionnaire, a measure of functionality, demonstrated good convergent validity. Significant correlations with depression and quality of life demonstrated good criterion validity. The WSAS also demonstrated strong internal consistency (α = .89), and the absence of floor and ceiling effects indicated good sensitivity of the instrument.
Conclusions
The results of the present study demonstrated that the German version of the WSAS has good psychometric properties comparable to other international versions of this scale. The findings recommend a global assessment of psychosocial functioning with the sum score of the WSAS.
Recreational exercising and self-reported cardiometabolic diseases in German people living with HIV
(2021)
Exercise is known for its beneficial effects on preventing cardiometabolic diseases (CMDs) in the general population. People living with the human immunodeficiency virus (PLWH) are prone to sedentarism, thus raising their already elevated risk of developing CMDs in comparison to individuals without HIV. The aim of this cross-sectional study was to determine if exercise is associated with reduced risk of self-reported CMDs in a German HIV-positive sample (n = 446). Participants completed a self-report survey to assess exercise levels, date of HIV diagnosis, CD4 cell count, antiretroviral therapy, and CMDs. Participants were classified into exercising or sedentary conditions. Generalized linear models with Poisson regression were conducted to assess the prevalence ratio (PR) of PLWH reporting a CMD. Exercising PLWH were less likely to report a heart arrhythmia for every increase in exercise duration (PR: 0.20: 95% CI: 0.10–0.62, p < 0.01) and diabetes mellitus for every increase in exercise session per week (PR: 0.40: 95% CI: 0.10–1, p < 0.01). Exercise frequency and duration are associated with a decreased risk of reporting arrhythmia and diabetes mellitus in PLWH. Further studies are needed to elucidate the mechanisms underlying exercise as a protective factor for CMDs in PLWH.