Modeling and analysis of cyber-physical systems are still challenging. One reason is that cyber-physical systems involve many different parts (cyber or physical), of different nature (discrete or... Show moreModeling and analysis of cyber-physical systems are still challenging. One reason is that cyber-physical systems involve many different parts (cyber or physical), of different nature (discrete or continuous), and in constant interaction via sensing and actuating.For instance, consider a group of robots, each running a program that takes decision based on the sequence of sensor readings. The sensors that equip a robot return the current position of the robot and the position of any adjacent obstacle. The interactionoccurring between each robot in the group cannot be derived solely from the specification of individual robots. If the field on which the robots roam changes its property, the same group of robots might sense different values, and therefore take different actions. Also, the time at which a robot acts and senses will affect the decision of each controller and will change the resulting collective behavior.This thesis proposes a compositional approach to the design and programming of interacting cyber-physical components. We present an algebra that provides a novel perspective on modeling interaction of cyber-physical components. Using our algebraic framework, one can design a complex cyber-physical system by first designing each part, and then specifying how the parts interact. We formalized the relation between our abstract semantic model and an implementation written in Maude, a programming language based on rewriting logic. We present some applications, including safety and liveness properties of a system consisting of a set of robots, each equipped with a battery, running on a shared field. Show less
This paper introduces the Bradley-Terry regression trunk model, a novel probabilistic approach for the analysis of preference data expressed through paired comparison rankings. In some cases, it... Show moreThis paper introduces the Bradley-Terry regression trunk model, a novel probabilistic approach for the analysis of preference data expressed through paired comparison rankings. In some cases, it may be reasonable to assume that the preferences expressed by individuals depend on their characteristics. Within the framework of tree-based partitioning, we specify a tree-based model estimating the joint effects of subject-specific covariates over and above their main effects. We, therefore, combine a tree-based model and the log-linear Bradley-Terry model using the outcome of the comparisons as response variable. The proposed model provides a solution to discover interaction effects when no a-priori hypotheses are available. It produces a small tree, called trunk, that represents a fair compromise between a simple interpretation of the interaction effects and an easy to read partition of judges based on their characteristics and the preferences they have expressed. We present an application on a real dataset following two different approaches, and a simulation study to test the model's performance. Simulations showed that the quality of the model performance increases when the number of rankings and objects increases. In addition, the performance is considerably amplified when the judges' characteristics have a high impact on their choices. Show less
Introduction: With the introduction of tyrosine kinase inhibitors and systemic antibodies, including immune checkpoint inhibitors, the survival of advanced-stage cancer patients has improved for... Show moreIntroduction: With the introduction of tyrosine kinase inhibitors and systemic antibodies, including immune checkpoint inhibitors, the survival of advanced-stage cancer patients has improved for many tumor types. These patients are increasingly referred for radiotherapy, but it is unclear whether radiotherapy combined with these drugs is safe. No international guidelines exist on whether or how to combine these drugs with radiotherapy. Therefore, we investigated the current clinical practice in the Netherlands regarding hypofractionated radiotherapy in patients using targeted drugs and immunotherapy.Materials and methods: We sent a survey to all 21 Dutch radiotherapy institutes. Dedicated radiation oncologists, medical oncologists and pulmonologists were asked to fill out the survey. The questions explored their familiarity with the combination of targeted drugs and immunotherapy with radiotherapy, the encountered clinical difficulties and factors influencing treatment decisions.Results: The survey was filled out by 54 respondents from 19 different institutes. The median annual number of patients per radiation oncologist referred for radiotherapy when using targeted drugs or immunotherapy was 10 and 15, respectively. Despite this high number, only 11% of the radiation oncologists stated that they had sufficient information (resources) for adequate treatment decision making. Among all physicians, 44% stated that there was insufficient knowledge within their institute regarding this topic. Only 17% stated that there was a multidisciplinary protocol available. The application of radiotherapy treatment adaptations (technique, dose, fractionation, field size) varied widely. Generally, there seemed to be no consensus regarding the expected toxicity of combined drug-radiotherapy treatments and the expected risk of tumor flare upon temporary drug discontinuation.Conclusion: There is no consensus amongst involved medical specialties on expected toxicity. Consequently, it is necessary to perform clinical studies examining the safety of combined drug-radiotherapy treatments, to add radiotherapy to phase I-III clinical trials for new drugs and to incorporate outcomes into multidisciplinary, evidence-based guidelines. Show less
Plant exudates appeared long time ago in the history line of life in the early Devonian. They are typical saps produced by specialized cells. They can be naturally excreted outside or right after... Show morePlant exudates appeared long time ago in the history line of life in the early Devonian. They are typical saps produced by specialized cells. They can be naturally excreted outside or right after plants are damaged or infected. Through time, diverse cultures recognized them as valuable sources of natural medicines. Of various types of plant exudates, the most outstanding are gums, mucilage, essential oils, oleoresins, resins, phloem like saps, and latexes. Regardless of their commercial importance, in the aspect of biology, plant exudates are believed to be involved in plant defense mechanisms, but their roles still remain unclear. In this thesis, based on diverse experiments, many features of plant exudates were unveiled. Interestingly, even if plant exudates possess a broad chemical diversity, their specialized biological functions resulted in less variation of their metabolomes as compared with their bearing tissues. This lower variation indicates that plant exudates might partake of a general-broad defense against herbivores and pathogens in their bearing tissues. This defense involves both mechanical and chemical traits which might complement and modulate each other, eventually resulting in a chemo-mechanical defense layer. Of the diverse chemicals in plant exudates, terpenes are one of the most common metabolites in these saps. Show less
Background Cognitive and motor-performance decline with age and the process is accelerated by decline in general health. In this study, we aimed to estimate the effects of COPD and HB levels on... Show moreBackground Cognitive and motor-performance decline with age and the process is accelerated by decline in general health. In this study, we aimed to estimate the effects of COPD and HB levels on cognitive and motor performance in the general older population and assess potential interaction. Methods The English Longitudinal Study of Aging is a population-based cohort study including measurements of lung-function and HB levels together with cognitive and motor performance testing. Data were collected from 5709 participants including three measurement time over eight years. COPD was defined using lung-function-parameters and clinical symptoms. HB was assessed continuously and low HB was defined using clinical anemia cutoffs. Linear mixed-effects regression models were used to quantify the associations of COPD and HB with outcome measures, both individually and in combination. Results Participants with both low HB and COPD demonstrated worse motor performance compared to individuals with only one exposure, resulting in up to 1 s (95%CI, 0.04-1.8) longer time needed to complete the five times sit to stand task than what would be expected based on purely additive effects. Additionally in individuals with COPD, the time to complete the motor-performance task per unit decrease in continuous HB levels was longer than in participants without COPD after full adjustment for confounding (up to 1.38 s/unit HB level, 95% CI: 0.65-2.11). Conclusion In persons with COPD low HB levels may contribute to low motor-performance in a supra additive fashion. Further studies should re-evaluate whether earlier treatment of lower HB in these individuals might be beneficial. Show less
Background Studies show mixed results on the association between depressive symptoms and adverse clinical outcomes in patients on dialysis therapy. Ethnicity may play a role in these heterogeneous... Show moreBackground Studies show mixed results on the association between depressive symptoms and adverse clinical outcomes in patients on dialysis therapy. Ethnicity may play a role in these heterogeneous results. No studies have investigated the interplay between ethnicity and depressive symptoms on clinical outcome in this patient population. This study aims to examine interaction between ethnicity and depressive symptoms on hospitalization and mortality in dialysis patients. Methods A multi-ethnic cohort in 10 dialysis centers included 687 dialysis patients between 2012 and 2017, with an average follow-up of 3.2 years. Depressive symptoms were measured using the Beck Depression Inventory. Interaction was assessed by investigating excess risk on an additive scale using both absolute rates and relative risks. Multivariable regression models included demographic, social, and clinical variables. Results Adverse outcomes are more pronounced in native patients, compared to immigrant patients. The risk for mortality and hospitalization is considerably higher in native patients compared to immigrants. An excess risk on an additive scale indicates the presence of possible causal interaction. Conclusions Depressive symptoms are a risk factor for hospitalization and mortality, especially in native dialysis patients. Adverse clinical events associated with depressive symptoms differ among ethnic groups. This differential association could play a role in the conflicting findings in literature. Ethnicity is an important factor when investigating depressive symptoms and clinical outcome in dialysis patients. Future research should focus on the possible mechanisms and pathways involved in these differential associations. Show less
Playing a musical instrument is generally considered to be a complex human behaviour involving the integration and coordination of a broad range of human functions such as perception, imagination,... Show morePlaying a musical instrument is generally considered to be a complex human behaviour involving the integration and coordination of a broad range of human functions such as perception, imagination, memory, information processing, emotion, communication, and dexterity. From this perspective, it seems only reasonable to assume that, in an age of informational and communicational abundance, this intrinsic multifacetedness manifests itself in numerous informational contact-points between musical practice and a variety of academic and para-academic fields which zoom in on these specific elements of musical activity. Joost Vanmaele’s dissertation is directed at carefully and systematically evaluating the position of musicianship in an age of informative abundance and connectedness, to consider ways of re-balancing and broadening its epistemic grounds and attuning its information systems, with a view to artistic development, enrichment and/or liberation. By proposing a Bio-Culturally informed Performers’ Practice of Western Art Music [BCiPP], an information- and dialogue-friendly, transdisciplinary space is created where musical activities are not considered as phenomena sui generis but rather as informable cultural instances or personal particularisations of the human capacity to meaningfully generate and react to temporally patterned sounds. The potential impact of BCiPP is put to the test in two case-studies. Show less
this thesis investigate the impact of land-use changes in conjunction with soil type and seasonal climatic variations on the diversity and dynamics of the soil microbiome in the Pampa ecosystem, a... Show morethis thesis investigate the impact of land-use changes in conjunction with soil type and seasonal climatic variations on the diversity and dynamics of the soil microbiome in the Pampa ecosystem, a subtropical grassland. To access the soil microbiome, a combined approach of sampling strategy, molecular fingerprinting, high-throughput sequencing, the separation of active and dormant populations, and network approach was employed. Land use and soil type are both drivers of bacteria; fungal and archaeal diversity and community structure, and also result in shifts in microbial biomass and metabolic activity. However, the measures of broad-scale functions did not converge with the community structures, evidencing that functioning and structure are not necessarily linked. A large overlap of microbial taxa between land usages were detected indicating the presence of a stable core microbiome resistant to anthropogenic disturbances. The dynamics of microbiome in response to seasonal cl imatic variations showed that moisture was the most important influencing community diversity and structure, with a larger effect on the active, dormant and total community than temperature. The network topology highlighted that each land-use system has a different and specific set of putative key species which might play a role intermediating microbial groups associations. Show less
Berg, H. van den; Paulussen, M.; Teuff, G. le; Judson, I.; Gelderblom, H.; Dirksen, U.; ... ; Euro-EWING99 Grp 2015
Why do certain incidents of serious violence end lethally whereas others do not? What role do personal characteristics of offenders and victims play and how do immediate situational factors... Show moreWhy do certain incidents of serious violence end lethally whereas others do not? What role do personal characteristics of offenders and victims play and how do immediate situational factors influence outcomes? So far, these questions have not been subjected to much empirical scrutiny in criminological studies. This study, conducted in the Netherlands, seeks to answer these questions by explicitly comparing violent events that ended lethally with those that ended non-lethally. By taking into account offenders’ and victims' personal characteristics as well as immediate situational factors, it offers a more complete understanding of differences in outcome. It shows that immediate situational factors contribute more significantly to the outcome of violent incidents than generally thought. The study also presents an overview of murder and manslaughter in the Netherlands and puts these figures into international perspective. A separate chapter compares different types of violent events. The findings provide crucial criminological insights which may also guide effor ts to reduce and prevent violent events from ending lethally in the future. Show less
Imaging subsurface structures with nanometer resolution has been a long-standing desire in science and industry. To obtain subsurface information one usually applies ultrasound, like e.g. in... Show moreImaging subsurface structures with nanometer resolution has been a long-standing desire in science and industry. To obtain subsurface information one usually applies ultrasound, like e.g. in echocardiography. Implementing ultrasound in an Atomic Force Microscope, a setup that is capable of imaging surfaces with atomic resolution, gives access to additional information. In particular, it is possible to image subsurface structures with nanometer resolution. However, it is not known why the subsurface structures become visible when applying ultrasound during the imaging with an Atomic Force Microscope. Based on a special excitation scheme, which makes use of two ultrasound excitations (one through the sample and one through the cantilever), Heterodyne Force Microscopy seems to be the most promising candidate for imaging deeply buried objects or structures with nanometer resolution. This thesis focuses on the poorly understood elements in Heterodyne Force Microscopy. We studied the ultrasound propagation in the sample, the dynamics of an ultrasonically excited cantilever near a sample that is also vibrating at a slightly diff erent frequency, and the generation of the heterodyne signal. The insight we gained in these matters allowed us to determine the contrast mechanism in a very well-de fined model sample, which contains gold nanoparticles buried in a soft polymer matrix. We show that the contrast in this system is determined by “friction at shaking nanoparticles”. Show less
This thesis describes the day to day interaction between propofol and midazolam as encountered in every day practice. The direct interaction of premedication given to patients before surgery has... Show moreThis thesis describes the day to day interaction between propofol and midazolam as encountered in every day practice. The direct interaction of premedication given to patients before surgery has profound implications. The propofol induction dose can be decreased with respect to the target BIS. Besides the interaction mechanisms of propofol and midazolam, the pharmacological backgrounds of propofol-opioid interactions are given. The future perspectives of PK-PD modeling and the use of additional informative techniques are given in the last chapter. Show less
Claessens, S.E.F.; Daskalakis, N.P.; Oitzl, M.S.; Kloet, E.R. de 2012
Synthetic glucocorticoids such as dexamethasone (DEX) are used to prevent or treat respiratory disorders in prematurely born infants. Besides the short-term benefit on lung development, numerous... Show moreSynthetic glucocorticoids such as dexamethasone (DEX) are used to prevent or treat respiratory disorders in prematurely born infants. Besides the short-term benefit on lung development, numerous human and animal studies have reported adverse neurodevelopmental side effects. In contrast, maternal care is known to exert a positive influence on neurodevelopmental outcome in rodents. The aim of the current study was therefore to investigate whether neonatal handling (days 1-21), known to induce maternal care, might serve as an intervention strategy modulating the adverse effects of DEX treatment (days 1-3). For this purpose we have measured the outcome of these early-life manipulations on development as well as adult endocrine and behavioral phenotype of male rats. Maternal care was observed during the first week of life and indeed enhanced in response to handling. Eye opening was accelerated and body weight reduced in DEX-treated animals. In adulthood, we report that handling ameliorated impaired spatial learning observed in DEX treated non-handled animals in the T-maze. Additionally, handling reduced susceptibility to the impact of DEX treatment in the water maze. Although DEX treatment and handling both resulted in enhanced negative feedback of the stress-induced corticosterone response and both reduced startle reactivity, the acquisition of fear was only reduced by handling, without effect of DEX. Interestingly, handling had a beneficial effect on pre-pulse inhibition, which was diminished after DEX treatment. In conclusion, these findings indicate that handling of the neonate enhances maternal care and attenuates specific DEX-induced alterations in the adult behavioral phenotype. (C) 2012 Elsevier Inc. All rights reserved. Show less
