666 results on '"Kappen, P."'
Search Results
2. Stochastic syncing in sinusoidally driven atomic orbital memory
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van Weerdenburg, Werner M. J., Osterhage, Hermann, Christianen, Ruben, Junghans, Kira, Domínguez, Eduardo, Kappen, Hilbert J., and Khajetoorians, Alexander Ako
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Condensed Matter - Mesoscale and Nanoscale Physics ,Condensed Matter - Disordered Systems and Neural Networks ,Condensed Matter - Statistical Mechanics - Abstract
Stochastically fluctuating multi-well systems as physical implementations of energy-based machine learning models promise a route towards neuromorphic hardware. Understanding the response of multi-well systems to dynamic input signals is crucial in this regard. Here, we investigate the stochastic response of binary orbital memory states derived from individual Fe and Co atoms on a black phosphorus surface to sinusoidal input voltages. Using scanning tunneling microscopy, we quantify the state residence times for DC and AC voltage drive with various input frequencies. We find that Fe and Co atoms both exhibit features of synchronization to the AC input, but only Fe atoms demonstrate a significant frequency-dependent change in the time-averaged state occupations. By modeling the underlying stochastic process, we show that the frequency response of the system is directly related to the DC voltage dependence of the state asymmetry. This relation provides a tunable way to induce population changes in stochastic systems and lays the foundation for understanding the response of multi-well systems to dynamical input signals.
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- 2023
3. Training Quantum Boltzmann Machines with the $\beta$-Variational Quantum Eigensolver
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Huijgen, Onno, Coopmans, Luuk, Najafi, Peyman, Benedetti, Marcello, and Kappen, Hilbert J.
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Quantum Physics - Abstract
The quantum Boltzmann machine (QBM) is a generative machine learning model for both classical data and quantum states. Training the QBM consists of minimizing the relative entropy from the model to the target state. This requires QBM expectation values which are computationally intractable for large models in general. It is therefore important to develop heuristic training methods that work well in practice. In this work, we study a heuristic method characterized by a nested loop: the inner loop trains the $\beta$-variational quantum eigensolver ($\beta$-VQE) by Liu et al (2021 Mach. Learn.: Sci. Technol.2 025011) to approximate the QBM expectation values; the outer loop trains the QBM to minimize the relative entropy to the target. We show that low-rank representations obtained by $\beta$-VQE provide an efficient way to learn low-rank target states, such as classical data and low-temperature quantum tomography. We test the method on both classical and quantum target data with numerical simulations of up to 10 qubits. For the cases considered here, the obtained QBMs can model the target to high fidelity. We implement a trained model on a physical quantum device. The approach offers a valuable route towards variationally training QBMs on near-term quantum devices., Comment: 9 pages, 11 figures
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- 2023
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4. The Fractional exhaled Nitric Oxide (FeNO)- test as add-on test in the diagnostic work-up of asthma: a study protocol
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Kaya, T. (Tuba), Braunstahl, G.J. (Gert-Jan), Veen, J.C.C.M. (Johannes) in ’t, Kappen, J.H. (Jasper), and Valk, J.P.M. (Hanna) van der
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- 2024
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5. Acoustic and prosodic speech features reflect physiological stress but not isolated negative affect: a multi-paradigm study on psychosocial stressors
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Kappen, Mitchel, Vanhollebeke, Gert, Van Der Donckt, Jonas, Van Hoecke, Sofie, and Vanderhasselt, Marie-Anne
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- 2024
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6. The Fractional exhaled Nitric Oxide (FeNO)- test as add-on test in the diagnostic work-up of asthma: a study protocol
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T. (Tuba) Kaya, G.J. (Gert-Jan) Braunstahl, J.C.C.M. (Johannes) in ’t Veen, J.H. (Jasper) Kappen, and J.P.M. (Hanna) van der Valk
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Asthma ,Diagnostics ,Bronchial provocation test ,Fractional exhaled Nitric Oxide-test ,Cost-effectiveness ,Burdensome ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Asthma is a common disease characterized by chronic inflammation of the lower airways, bronchial hyperactivity, and (reversible) airway obstruction. The Global Initiative of Asthma Guideline recommends a flowchart to diagnose asthma with first-step spirometry with reversibility and a bronchial challenge test (BPT) with histamine or methacholine as a second step [1]. The BPT is considered burdensome, time-consuming for patients and staff, can cause side effects, and is expensive. In addition, this test strongly encumbers lung function capacity. Elevated Nitric Oxide (NO) is associated with airway eosinophilic inflammation in asthma patients and can be measured in exhaled air with the Fractional exhaled (Fe) NO-test. This low-burden FeNO-test could be used as an ‘add-on’ test in asthma diagnostics [2, 3]. Methods and analysis This multi-center prospective study (Trial number: NCT06230458) compares the ‘standard asthma diagnostic work-up’ (spirometry with reversibility and BPT) to the ‘new asthma diagnostics work-up’ (FeNO-test as an intermediate step between the spirometry with reversibility and the BPT), intending to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness and reduced burden to the patient and health care. The cost reduction of incorporating the FeNO-test in the new diagnostic algorithm will be established by the number of theoretically avoided BPT. The decrease in burden will be studied by calculating differences in the Visual Analogue Scale (VAS) -score and Asthma Quality of Life Questionnaire (AQLQ) -score after the BPT and FeNO-test with an independent T-test. The accuracy of the FeNO-test will be calculated by comparing the FeNO-test outcomes to the (gold standard) BPTs outcomes in terms of sensitivity and specificity. The intention is to include 171 patients. Ethics and dissemination The local medical ethics committee approved the proposed study and is considered a low-burden and risk-low study. The local medical ethics committee registration number: R23.005. Strengths and limitations of this study Strengths: This is the first study that investigates the value of the FeNO-test (cut off ≥ 50 ppb) as an add-on test, to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness, and reduced burden on the patient and health care. Limitations: High FeNO levels may also be observed in other diseases such as eosinophilic chronic bronchitis and allergic rhinitis. The FeNO-test can be used to rule in a diagnosis of asthma with confidence, however, due to the poor sensitivity it is not suitable to rule out asthma.
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- 2024
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7. Speech as a promising biosignal in precision psychiatry.
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Kappen, Mitchel, Vanderhasselt, Marie-Anne, and Slavich, George
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Assessment ,Biomarker ,Disease ,Health ,Precision medicine ,Speech ,Stress ,Voice ,Humans ,Speech ,Schizophrenia ,Stress ,Psychological ,Longitudinal Studies ,Psychiatry - Abstract
Health research and health care alike are presently based on infrequent assessments that provide an incomplete picture of clinical functioning. Consequently, opportunities to identify and prevent health events before they occur are missed. New health technologies are addressing these critical issues by enabling the continual monitoring of health-related processes using speech. These technologies are a great match for the healthcare environment because they make high-frequency assessments non-invasive and highly scalable. Indeed, existing tools can now extract a wide variety of health-relevant biosignals from smartphones by analyzing a persons voice and speech. These biosignals are linked to health-relevant biological pathways and have shown promise in detecting several disorders, including depression and schizophrenia. However, more research is needed to identify the speech signals that matter most, validate these signals against ground-truth outcomes, and translate these data into biomarkers and just-in-time adaptive interventions. We discuss these issues herein by describing how assessing everyday psychological stress through speech can help both researchers and health care providers monitor the impact that stress has on a wide variety of mental and physical health outcomes, such as self-harm, suicide, substance abuse, depression, and disease recurrence. If done appropriately and securely, speech is a novel digital biosignal that could play a key role in predicting high-priority clinical outcomes and delivering tailored interventions that help people when they need it most.
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- 2023
8. Why adiabatic quantum annealing is unlikely to yield speed-up
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Villanueva, Aarón, Najafi, Peyman, and Kappen, Hilbert J.
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Quantum Physics - Abstract
We study quantum annealing for combinatorial optimization with Hamiltonian $H = z H_f + H_0$ where $H_f$ is diagonal, $H_0=-|\phi \rangle \langle \phi|$ is the equal superposition state projector and $z$ the annealing parameter. We analytically compute the minimal spectral gap as $\mathcal{O}(1/\sqrt{N})$ with $N$ the total number of states and its location $z_*$. We show that quantum speed-up requires an annealing schedule which demands a precise knowledge of $z_*$, which can be computed only if the density of states of the optimization problem is known. However, in general the density of states is intractable to compute, making quadratic speed-up unfeasible for any practical combinatoric optimization problems. We conjecture that it is likely that this negative result also applies for any other instance independent transverse Hamiltonians such as $H_0 = -\sum_{i=1}^n \sigma_i^x$., Comment: 23 pages, 6 figures, updated to published version
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- 2022
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9. Efficient inference in the transverse field Ising model
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Domínguez, E. and Kappen, H. J.
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Condensed Matter - Disordered Systems and Neural Networks - Abstract
In this paper we introduce an approximate method to solve the quantum cavity equations for transverse field Ising models. The method relies on a projective approximation of the exact cavity distributions of imaginary time trajectories (paths). A key feature, novel in the context of similar algorithms, is the explicit separation of the classical and quantum parts of the distributions. Numerical simulations show accurate results in comparison with the sampled solution of the cavity equations, the exact diagonalization of the Hamiltonian (when possible) and other approximate inference methods in the literature. The computational complexity of this new algorithm scales linearly with the connectivity of the underlying lattice, enabling the study of highly connected networks, as the ones often encountered in quantum machine learning problems.
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- 2022
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10. Severe COPD: Multidisciplinary Consultation to Get the Right Care at the Right Place
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Hekking PP, van Meggelen M, Lie WJ, Hoek RAS, van Ranst D, van der Kleij SCJ, Seghers L, Kappen J, Braunstahl GJ, and In 't Veen J
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Diseases of the respiratory system ,RC705-779 - Abstract
Pieter-Paul Hekking,1 Monique van Meggelen,1 W Johan Lie,2 Rogier Arnaud Sebastiaan Hoek,3,4 Dirk van Ranst,5 Stephan Cornelis Johan van der Kleij,6 Leonard Seghers,4 Jasper Kappen,1,7 Gert-Jan Braunstahl,1,8 Johannes In ’t Veen1 On behalf of Severe Asthma & COPD Network South West Netherlands1Centre of Excellence for Asthma, COPD & Respiratory Allergy, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands; 2Department of Pulmonary Medicine, Maasstad Hospital, Rotterdam, the Netherlands; 3Department of Pulmonary Medicine, Bravis Hospital, Bergen op Zoom, the Netherlands; 4Department of Pulmonary Medicine, Erasmus MC Transplant Institute, Rotterdam, the Netherlands; 5Revant, Pulmonary Rehabilitation, Breda, the Netherlands; 6Department of Intensive Care Medicine and Home Mechanical Ventilation, Rotterdam, the Netherlands; 7Department of National Heart and Lung Institute, Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Imperial College London, London, UK; 8Department of Pulmonary Medicine, Rotterdam, the NetherlandsCorrespondence: Pieter-Paul Hekking, Franciscus Gasthuis & Vlietland, Centre of excellence for asthma, COPD & Respiratory allergy, Kleiweg, 500, Rotterdam, 3045 PM, the Netherlands, Email p.hekking@franciscus.nl
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- 2024
11. Acoustic and prosodic speech features reflect physiological stress but not isolated negative affect: a multi-paradigm study on psychosocial stressors
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Mitchel Kappen, Gert Vanhollebeke, Jonas Van Der Donckt, Sofie Van Hoecke, and Marie-Anne Vanderhasselt
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Medicine ,Science - Abstract
Abstract Heterogeneity in speech under stress has been a recurring issue in stress research, potentially due to varied stress induction paradigms. This study investigated speech features in semi-guided speech following two distinct psychosocial stress paradigms (Cyberball and MIST) and their respective control conditions. Only negative affect increased during Cyberball, while self-reported stress, skin conductance response rate, and negative affect increased during MIST. Fundamental frequency (F0), speech rate, and jitter significantly changed during MIST, but not Cyberball; HNR and shimmer showed no expected changes. The results indicate that observed speech features are robust in semi-guided speech and sensitive to stressors eliciting additional physiological stress responses, not solely decreases in negative affect. These differences between stressors may explain literature heterogeneity. Our findings support the potential of speech as a stress level biomarker, especially when stress elicits physiological reactions, similar to other biomarkers. This highlights its promise as a tool for measuring stress in everyday settings, considering its affordability, non-intrusiveness, and ease of collection. Future research should test these results' robustness and specificity in naturalistic settings, such as freely spoken speech and noisy environments while exploring and validating a broader range of informative speech features in the context of stress.
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- 2024
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12. Pre-asthma: a useful concept? A EUFOREA paper. Part 2—late onset eosinophilic asthma
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G. K. Scadding, C. Gray, D. M. Conti, M. McDonald, V. Backer, G. Scadding, M. Bernal-Sprekelsen, E. De Corso, Z. Diamant, C. Hopkins, M. Jesenak, P. Johansen, J. Kappen, J. Mullol, D. Price, S. Quirce, S. Reitsma, S. Toppila-Salmi, B. Senior, J. P. Thyssen, U. Wahn, and P. W. Hellings
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late onset asthma ,non-allergic rhinitis ,chronic rhinosinusitis with nasal polyps ,eosinophils ,mast cells ,virulence genes ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The concept of pre-diabetes has led to provision of measures to reduce disease progression through identification of subjects at risk of diabetes. We previously considered the idea of pre-asthma in relation to allergic asthma and considered that, in addition to the need to improve population health via multiple measures, including reduction of exposure to allergens and pollutants and avoidance of obesity, there are several possible specific means to reduce asthma development in those most at risk (pre- asthma). The most obvious is allergen immunotherapy (AIT), which when given for allergic rhinitis (AR) has reasonable evidence to support asthma prevention in children (2) but also needs further study as primary prevention. In this second paper we explore the possibilities for similar actions in late onset eosinophilic asthma.
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- 2024
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13. Effects of acute psychosocial stress on source level EEG power and functional connectivity measures
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Vanhollebeke, Gert, Kappen, Mitchel, De Raedt, Rudi, Baeken, Chris, van Mierlo, Pieter, and Vanderhasselt, Marie-Anne
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- 2023
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14. The effect of proactive versus reactive treatment of hypotension on postoperative disability and outcome in surgical patients under anaesthesia (PRETREAT): clinical trial protocol and considerations
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Matthijs Kant, Wilton A. van Klei, Markus W. Hollmann, Denise P. Veelo, Teus H. Kappen, Eline de Klerk, Lisette Vernooij, Luuk C. Otterspoor, Geert-Jan E. Cromheecke, Marlous Huijzer, Jannie Witziers, Lotte E. Terwindt, Tim Bastiaanse, Rogier V. Immink, Magnus Strypet, Niek H. Sperna Weiland, Marije Wijnberge, Marc G.H. Besselink, Lisette M. Vernooij, Yvonne C. Janmaat, and Annemarie Akkermans
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blood pressure ,intraoperative hypotension ,myocardial injury ,organ injury ,renal injury ,Anesthesiology ,RD78.3-87.3 - Abstract
Background: Intraoperative hypotension has been extensively studied for its association with adverse outcomes. However, small sample sizes and methodological issues limit the causal inference that can be drawn. Methods: In this multicentre, adaptive, randomised controlled trial, we will include 5000 adult inpatients scheduled for elective non-cardiac surgery under general or central neuraxial anaesthesia. Patients will be either randomly allocated to the intervention or care-as-usual group using computer-generated blocks of four, six, or eight, with an allocation ratio of 1:1. In the intervention arm patients will be divided into low-, intermediate-, and high-risk groups based on their likelihood to experience intraoperative hypotension, with resulting mean blood pressure targets of 70, 80, and 90 mm Hg, respectively. Anaesthesia teams will be provided with a clinical guideline on how to keep patients at their target blood pressure. During the first 6 months of the trial the intervention strategy will be evaluated and further revised in adaptation cycles of 3 weeks if necessary, to improve successful impact on the clinical process. The primary outcome is postoperative disability after 6 months measured with the World Health Organization Disability Assessment Score (WHODAS) 2.0 questionnaire. Ethics and dissemination: This study protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht (20–749) and all protocol amendments will be communicated to the Medical Ethics Committee. The study protocol is in adherence with the Declaration of Helsinki and the guideline of Good Clinical Practice. Dissemination plans include publication in a peer-reviewed journal. Clinical trial registration: The Dutch Trial Register, NL9391. Registered on 22 March 2021.
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- 2024
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15. Posterior Müller Muscle-Conjunctival Resection as a First Step to Treat Eyelid Ptosis: Clinical Results and Treatment Algorithm
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Maarten Fechner, Isabelle Francisca Petronella Maria Kappen, Joep Antonius Franciscus van Rooij, and Berend van der Lei
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Surgery ,RD1-811 - Abstract
Abstract BackgroundThe posterior Müller muscle-conjunctival resection (MMCR) procedure is a straightforward procedure for the correction of eyelid ptosis with a relatively short operating time and fast recovery. Traditionally, its use was limited to patients with mild involutional ptosis and good levator function and a positive phenylephrine test result. ObjectivesTo evaluate the efficacy of the MMCR procedure as a primary step to treat eyelid ptosis with varying etiology and severity, including patients with more severe ptosis and moderate levator function, and to produce a treatment algorithm. MethodsA retrospective analysis of the results of 34 patients, comprising 56 operated eyelids, treated with the MMCR procedure for eyelid ptotis between 2016 and 2018, was performed. Preoperative and postoperative pictures were analyzed for determining the margin-to-reflex distance (MRD1), symmetry, and complications. ResultsWe found a mean preoperative MRD1 of 1.3 mm (SD 1.1) and postoperative MRD1 of 3.2 mm (SD 1.0). The mean postoperative MRD1 for unilateral and bilateral cases was 3.4 (SD 0.8) and 3.2 (SD 1.1), respectively. Only 2 patients (5.9%) had an asymmetrical postoperative result (>1.0 mm MRD1 difference), and both were unilateral cases. Complications were scarce: only 1 patient (2.9%) developed dry eyes and 2 patients experienced temporary discomfort from the conjunctival sutures. ConclusionsThe MMCR procedure appears to be an excellent procedure as a primary step to correct eyelid ptosis with varying etiologies and severity, due to its low risk of asymmetry, short learning curve, and high success rate. A flow chart as treatment algorithm is provided for clinical decision making. Level of Evidence: 4
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- 2024
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16. Pre-asthma: a useful concept for prevention and disease-modification? A EUFOREA paper. Part 1—allergic asthma
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G. K. Scadding, M. McDonald, V. Backer, G. Scadding, M. Bernal-Sprekelsen, D. M. Conti, E. De Corso, Z. Diamant, C. Gray, C. Hopkins, M. Jesenak, P. Johansen, J. Kappen, J. Mullol, D. Price, S. Quirce, S. Reitsma, S. Salmi, B. Senior, J. P. Thyssen, U. Wahn, and P. W. Hellings
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pre-asthma ,asthma ,quality of life ,asthma natural history ,predisposition ,risk factors ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Asthma, which affects some 300 million people worldwide and caused 455,000 deaths in 2019, is a significant burden to suffers and to society. It is the most common chronic disease in children and represents one of the major causes for years lived with disability. Significant efforts are made by organizations such as WHO in improving the diagnosis, treatment and monitoring of asthma. However asthma prevention has been less studied. Currently there is a concept of pre- diabetes which allows a reduction in full blown diabetes if diet and exercise are undertaken. Similar predictive states are found in Alzheimer's and Parkinson's diseases. In this paper we explore the possibilities for asthma prevention, both at population level and also investigate the possibility of defining a state of pre-asthma, in which intensive treatment could reduce progression to asthma. Since asthma is a heterogeneous condition, this paper is concerned with allergic asthma. A subsequent one will deal with late onset eosinophilic asthma.
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- 2024
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17. Invited Discussion on: Changing Aesthetic Surgery Interest in Men: An 18-Year Analysis
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Hodgkinson, Darryl J. and Kappen, Isabelle Francisca Petronella Maria
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- 2023
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18. Effects of acute psychosocial stress on source level EEG power and functional connectivity measures
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Gert Vanhollebeke, Mitchel Kappen, Rudi De Raedt, Chris Baeken, Pieter van Mierlo, and Marie-Anne Vanderhasselt
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Medicine ,Science - Abstract
Abstract The usage of EEG to uncover the influence of psychosocial stressors (PSSs) on neural activity has gained significant attention throughout recent years, but the results are often troubled by confounding stressor types. To investigate the effect of PSSs alone on neural activity, we employed a paradigm where participants are exposed to negative peer comparison as PSS, while other possible stressors are kept constant, and compared this with a condition where participants received neutral feedback. We analyzed commonly used sensor level EEG indices (frontal theta, alpha, and beta power) and further investigated whether source level power and functional connectivity (i.e., the temporal dependence between spatially seperated brain regions) measures, which have to our knowledge not yet been used, are more sensitive to PSSs than sensor level-derived EEG measures. Our results show that on sensor level, no significant frontal power changes are present (all p’s > 0.16), indicating that sensor level frontal power measures are not sensitive enough to be affected by only PSSs. On source level, we find increased alpha power (indicative of decreased cortical activity) in the left- and right precuneus and right posterior cingulate cortex (all p’s
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- 2023
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19. Adaptive Smoothing Path Integral Control
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Thalmeier, Dominik, Kappen, Hilbert J., Totaro, Simone, and Gómez, Vicenç
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Electrical Engineering and Systems Science - Systems and Control ,Computer Science - Machine Learning - Abstract
In Path Integral control problems a representation of an optimally controlled dynamical system can be formally computed and serve as a guidepost to learn a parametrized policy. The Path Integral Cross-Entropy (PICE) method tries to exploit this, but is hampered by poor sample efficiency. We propose a model-free algorithm called ASPIC (Adaptive Smoothing of Path Integral Control) that applies an inf-convolution to the cost function to speedup convergence of policy optimization. We identify PICE as the infinite smoothing limit of such technique and show that the sample efficiency problems that PICE suffers disappear for finite levels of smoothing. For zero smoothing this method becomes a greedy optimization of the cost, which is the standard approach in current reinforcement learning. We show analytically and empirically that intermediate levels of smoothing are optimal, which renders the new method superior to both PICE and direct cost-optimization., Comment: 23 pages, 5 figures, NeurIPS 2019 Optimization Foundations of Reinforcement Learning Workshop (OptRL 2019)
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- 2020
20. An atomic Boltzmann machine capable of on-chip learning
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Kiraly, Brian, Knol, Elze J., Kappen, Hilbert J., and Khajetoorians, Alexander A.
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Condensed Matter - Mesoscale and Nanoscale Physics ,Condensed Matter - Disordered Systems and Neural Networks ,Condensed Matter - Materials Science - Abstract
The Boltzmann Machine (BM) is a neural network composed of stochastically firing neurons that can learn complex probability distributions by adapting the synaptic interactions between the neurons. BMs represent a very generic class of stochastic neural networks that can be used for data clustering, generative modelling and deep learning. A key drawback of software-based stochastic neural networks is the required Monte Carlo sampling, which scales intractably with the number of neurons. Here, we realize a physical implementation of a BM directly in the stochastic spin dynamics of a gated ensemble of coupled cobalt atoms on the surface of semiconducting black phosphorus. Implementing the concept of orbital memory utilizing scanning tunnelling microscopy, we demonstrate the bottom-up construction of atomic ensembles whose stochastic current noise is defined by a reconfigurable multi-well energy landscape. Exploiting the anisotropic behaviour of black phosphorus, we build ensembles of atoms with two well-separated intrinsic time scales that represent neurons and synapses. By characterizing the conditional steady-state distribution of the neurons for given synaptic configurations, we illustrate that an ensemble can represent many distinct probability distributions. By probing the intrinsic synaptic dynamics, we reveal an autonomous reorganization of the synapses in response to external electrical stimuli. This self-adaptive architecture paves the way for on-chip learning directly in atomic-scale machine learning hardware.
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- 2020
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21. Decision Support in the Context of a Complex Decision Situation
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Kappen, Teus H., Noordegraaf, Mirko, van Klei, Wilton A., Moons, Karel G. M., and Kalkman, Cor J.
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Computer Science - Human-Computer Interaction - Abstract
The aim of a clinical decision support tool is to reduce the complexity of clinical decisions. However, when decision support tools are poorly implemented they may actually confuse physicians and complicate clinical care. This paper argues that information from decision support tools is often removed from the clinical context of the targeted decisions. Physicians largely depend on clinical context to handle the complexity of their day-to-day decisions. Clinical context enables them to take into account all ambiguous information and patient preferences. Decision support tools that provide analytic information to physicians, without its context, may then complicate the decision process of physicians. It is likely that the joint forces of physicians and technology will produce better decisions than either of them exclusively: after all, they do have different ways of dealing with the complexity of a decision and are thus complementary. Therefore, the future challenges of decision support do not only reside in the optimization of the predictive value of the underlying models and algorithms, but equally in the effective communication of information and its context to doctors.
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- 2020
22. Differential responses to maternal diabetes in embryo and visceral yolk sac
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J. Michael Salbaum, Kirsten P. Stone, Claudia Kruger, and Claudia Kappen
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diabetic pregnancy ,neural tube defect ,somite number ,somite stage ,RNA-seq ,visceral yolk sac ,Biology (General) ,QH301-705.5 - Abstract
Introduction: Maternal diabetes during pregnancy is well known to be associated with a higher risk for structural birth defects in the offspring. Recent searches for underlying mechanisms have largely focused on aberrant processes in the embryo itself, although prior research in rodent models implicated dysfunction also of the visceral yolk sac. The objective of our research was to investigate both tissues within the conceptus simultaneously.Methods: We conducted unbiased transcriptome profiling by RNA sequencing on pairs of individual yolk sacs and their cognate embryos, using the non-obese diabetic (NOD) mouse model. The analysis was performed at gestational day 8.5 on morphologically normal specimen to circumvent confounding by defective development.Results: Even with large sample numbers (n = 33 in each group), we observed considerable variability of gene expression, primarily driven by exposure to maternal diabetes, and secondarily by developmental stage of the embryo. Only a moderate number of genes changed expression in the yolk sac, while in the embryo, the exposure distinctly influenced the relationship of gene expression levels to developmental progression, revealing a possible role for altered cell cycle regulation in the response. Also affected in embryos under diabetic conditions were genes involved in cholesterol biosynthesis and NAD metabolism pathways.Discussion: Exposure to maternal diabetes during gastrulation changes transcriptomic profiles in embryos to a substantially greater effect than in the corresponding yolk sacs, indicating that despite yolk sac being of embryonic origin, different mechanisms control transcriptional activity in these tissues. The effects of maternal diabetes on expression of many genes that are correlated with developmental progression (i.e. somite stage) highlight the importance of considering developmental maturity in the interpretation of transcriptomic data. Our analyses identified cholesterol biosynthesis and NAD metabolism as novel pathways not previously implicated in diabetic pregnancies. Both NAD and cholesterol availability affect a wide variety of cellular signaling processes, and can be modulated by diet, implying that prevention of adverse outcomes from diabetic pregnancies may require broad interventions, particularly in the early stages of pregnancy.
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- 2023
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23. The effect of recorded music on pain endurance (CRESCENDo) – A randomized controlled trial
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Ryan Billar, Pablo Kappen, Sepehr Mohammadian, Corinne van den Berg, Yolanda de Rijke, Erica van den Akker, Joost van Rosmalen, J. Marco Schnater, Arnaud Vincent, Clemens Dirven, Markus Klimek, René Wijnen, Johannes Jeekel, Frank Huygen, and Jitske Tiemensma
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Music ,Stress ,Hypothalamic-pituitary-adrenocortical axis ,Pain endurance ,Tolerance ,Anxiety ,Other systems of medicine ,RZ201-999 - Abstract
Introduction: Clarifying the effect of music on pain endurance in an experimental design could aid in how music should be applied during both surgical and non-surgical interventions. This study aims to investigate the effect of music on pain endurance and the involvement of the sympathetic adrenomedullary axis (SAM) and the hypothalamic-pituitary-adrenocortical axis (HPA). Materials and methods: In this randomized controlled trial all participants received increasing electric stimuli through their non-dominant index finger. Participants were randomly assigned to the music group (M) receiving a 20-minute music intervention or control group (C) receiving a 20-minute resting period. The primary outcome was pain endurance, defined as amount milliampere tolerated. Secondary outcomes included anxiety level, SAM-axis based on heart rate variability (HRV) and salivary alpha-amylase, and HPA-axis activity based on salivary cortisol. Results: In the intention-to-treat analysis, the effect of music on pain tolerance did not statistically differ between the M and C group. A significant positive effect of music on pain endurance was noted after excluding participants with a high skin impedance (p = 0.013, CI 0.35; 2.85). Increased HRV was observed in the M-group compared to the C-group for SDNN (B/95%CI:13.80/2.22;25.39, p = 0.022), RMSSD (B/95%CI:15.97/1.64;30.31, p = 0.032), VLF (B/95%CI:212.08/60.49;363.67, p = 0.008) and HF (B/95%CI:821.15/150.78;1491.52, p = 0.0190). No statistical significance was observed in other secondary outcomes. Conclusions: The effect of the music intervention on pain endurance was not statistically significant in the intention-to-treat analysis. The subgroup analyses revealed an increase in pain endurance in the music group after correcting for skin impedance, which could be attributed to increased parasympathetic activation.
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- 2023
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24. High-accuracy transmission and fluorescence XAFS of zinc at 10 K, 50 K, 100 K and 150 K using the hybrid technique
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Marcus W. John, Daniel Sier, Ruwini S. K. Ekanayake, Martin J. Schalken, Chanh Q. Tran, Bernt Johannessen, Martin D. de Jonge, Peter Kappen, and Christopher T. Chantler
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xafs ,hybrid technique ,transmission and fluorescence ,zinc ,thermal evolution ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 ,Crystallography ,QD901-999 - Abstract
The most accurate measurements of the mass attenuation coefficient for metals at low temperature for the zinc K-edge from 9.5 keV to 11.5 keV at temperatures of 10 K, 50 K, 100 K and 150 K using the hybrid technique are reported. This is the first time transition metal X-ray absorption fine structure (XAFS) has been studied using the hybrid technique and at low temperatures. This is also the first hybrid-like experiment at the Australian Synchrotron. The measured transmission and fluorescence XAFS spectra are compared and benchmarked against each other with detailed systematic analyses. A recent method for modelling self-absorption in fluorescence has been adapted and applied to a solid sample. The XAFS spectra are analysed using eFEFFIT to provide a robust measurement of the evolution of nanostructure, including such properties as net thermal expansion and mean-square relative displacement. This work investigates crystal dynamics, nanostructural evolution and the results of using the Debye and Einstein models to determine atomic positions. Accuracies achieved, when compared with the literature, exceed those achieved by both relative and differential XAFS, and represent a state-of-the-art for future structural investigations. Bond length uncertainties are of the order of 20–40 fm.
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- 2023
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25. Training quantum Boltzmann machines with the β-variational quantum eigensolver
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Onno Huijgen, Luuk Coopmans, Peyman Najafi, Marcello Benedetti, and Hilbert J Kappen
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quantum Boltzmann machines ,beta-variational quantum eigensolver ,quantum state preparation ,quantum tomography ,quantum machine learning ,Computer engineering. Computer hardware ,TK7885-7895 ,Electronic computers. Computer science ,QA75.5-76.95 - Abstract
The quantum Boltzmann machine (QBM) is a generative machine learning model for both classical data and quantum states. Training the QBM consists of minimizing the relative entropy from the model to the target state. This requires QBM expectation values which are computationally intractable for large models in general. It is therefore important to develop heuristic training methods that work well in practice. In this work, we study a heuristic method characterized by a nested loop: the inner loop trains the β -variational quantum eigensolver ( β -VQE) by Liu et al (2021 Mach. Learn.: Sci. Technol. 2 025011) to approximate the QBM expectation values; the outer loop trains the QBM to minimize the relative entropy to the target. We show that low-rank representations obtained by β -VQE provide an efficient way to learn low-rank target states, such as classical data and low-temperature quantum tomography. We test the method on both classical and quantum target data with numerical simulations of up to 10 qubits. For the cases considered here, the obtained QBMs can model the target to high fidelity. We implement a trained model on a physical quantum device. The approach offers a valuable route towards variationally training QBMs on near-term quantum devices.
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- 2024
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26. Identification of a Chondrocyte-Specific Enhancer in the Hoxc8 Gene
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Stephania A. Cormier and Claudia Kappen
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reporter transgene ,LacZ ,enhancer ,combinatorial regulation ,cartilage ,perichondria ,Biology (General) ,QH301-705.5 - Abstract
Hox genes encode transcription factors whose roles in patterning animal body plans during embryonic development are well-documented. Multiple studies demonstrate that Hox genes continue to act in adult cells, in normal differentiation, in regenerative processes, and, with abnormal expression, in diverse types of cancers. However, surprisingly little is known about the regulatory mechanisms that govern Hox gene expression in specific cell types, as they differentiate during late embryonic development, and in the adult organism. The murine Hoxc8 gene determines the identity of multiple skeletal elements in the lower thoracic and lumbar region and continues to play a role in the proliferation and differentiation of cells in cartilage as the skeleton matures. This study was undertaken to identify regulatory elements in the Hoxc8 gene that control transcriptional activity, specifically in cartilage-producing chondrocytes. We report that an enhancer comprising two 416 and 224 bps long interacting DNA elements produces reporter gene activity when assayed on a heterologous transcriptional promoter in transgenic mice. This enhancer is distinct in spatial, temporal, and molecular regulation from previously identified regulatory sequences in the Hoxc8 gene that control its expression in early development. The identification of a tissue-specific Hox gene regulatory element now allows mechanistic investigations into Hox transcription factor expression and function in differentiating cell types and adult tissues and to specifically target these cells during repair processes and regeneration.
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- 2024
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27. Wissenschaftsausbildung im Medizinstudium: Das Oldenburger Datenanalyseprojekt als Umsetzungsbeispiel [Lessons learned]
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Timmer, Antje, Neuser, Johanna, Uslar, Verena, Kappen, Sanny, Seipp, Alexander, Tiles-Sar, Natalia, de Sordi, Dominik, Beckhaus, Julia, and Otto-Sobotka, Fabian
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science education ,medical curriculum ,teaching goals ,epidemiology and biometry ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Introduction: According to the Master Plan 2020, science education will play a critical role in future medical curricula. Science modules have already been implemented at many locations. Other medical faculties will follow in the next few years, as legislation is expected to make recommendations of the national competence-based learning objectives curriculum for medicine (NKLM) mandatory. This article aims to present an implementation example from epidemiology and biometry as a contribution to the didactic discussions within the data sciences in medicine. Project description: We report on our experiences with a data analysis project for second-year medical students, which has been compulsory at the Faculty of Medicine and Health Sciences since 2019. The project is intended to train the scientific skills required from the subjects of epidemiology and biometry for student research projects. Emphasis is placed on responsible data handling, transparency, and reproducibility. For example, the writing of a statistical analysis plan is required prior to data access. Improved standardization of materials, optional use of the English language, and digital support will be implemented to help manage the project when student numbers increase. Discussion: The experience from five years is very positive, although a formal evaluation of the learning success is still pending. Current challenges concern staffing, additional time and supervision requirements for those students who do statistical programming with R, and improved integration into the medical curriculum.
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- 2023
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28. Prognostic factors for multi-organ dysfunction in pediatric oncology patients admitted to the pediatric intensive care unit
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Marijn Soeteman, Marta F. Fiocco, Joppe Nijman, Casper W. Bollen, Maartje M. Marcelis, Ellen Kilsdonk, Edward E. S. Nieuwenhuis, Teus H. Kappen, Wim J. E. Tissing, and Roelie M. Wösten-van Asperen
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pediatric oncology ,intensive care unit ,multi-organ dysfunction ,critical care ,prognosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundPediatric oncology patients who require admission to the pediatric intensive care unit (PICU) have worse outcomes compared to their non-cancer peers. Although multi-organ dysfunction (MOD) plays a pivotal role in PICU mortality and morbidity, risk factors for MOD have not yet been identified. We aimed to identify risk factors at PICU admission for new or progressive MOD (NPMOD) during the first week of PICU stay.MethodsThis retrospective cohort study included all pediatric oncology patients aged 0 to 18 years admitted to the PICU between June 2018 and June 2021. We used the recently published PODIUM criteria for defining multi-organ dysfunction and estimated the association between covariates at PICU baseline and the outcome NPMOD using a multivariable logistic regression model, with PICU admission as unit of study. To study the predictive performance, the model was internally validated by using bootstrap.ResultsA total of 761 PICU admissions of 571 patients were included. NPMOD was present in 154 PICU admissions (20%). Patients with NPMOD had a high mortality compared to patients without NPMOD, 14% and 1.0% respectively. Hemato-oncological diagnosis, number of failing organs and unplanned admission were independent risk factors for NPMOD. The prognostic model had an overall good discrimination and calibration.ConclusionThe risk factors at PICU admission for NPMOD may help to identify patients who may benefit from closer monitoring and early interventions. When applying the PODIUM criteria, we found some opportunities for fine-tuning these criteria for pediatric oncology patients, that need to be validated in future studies.
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- 2023
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29. Implementing perceptron models with qubits
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Wiersema, Roeland and Kappen, H. J.
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Quantum Physics - Abstract
We propose a method for learning a quantum probabilistic model of a perceptron. By considering a cross entropy between two density matrices we can learn a model that takes noisy output labels into account while learning. A multitude of proposals already exist that aim to utilize the curious properties of quantum systems to build a quantum perceptron, but these proposals rely on a classical cost function for the optimization procedure. We demonstrate the usage of a quantum equivalent of the classical log-likelihood, which allows for a quantum model and training procedure. We show that this allows us to better capture noisyness in data compared to a classical perceptron. By considering entangled qubits we can learn nonlinear separation boundaries, such as XOR.
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- 2019
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30. Acoustic speech features in social comparison: how stress impacts the way you sound
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Mitchel Kappen, Jonas van der Donckt, Gert Vanhollebeke, Jens Allaert, Vic Degraeve, Nilesh Madhu, Sofie Van Hoecke, and Marie-Anne Vanderhasselt
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Medicine ,Science - Abstract
Abstract The use of speech as a digital biomarker to detect stress levels is increasingly gaining attention. Yet, heterogeneous effects of stress on specific acoustic speech features have been observed, possibly due to previous studies’ use of different stress labels/categories and the lack of solid stress induction paradigms or validation of experienced stress. Here, we deployed a controlled, within-subject psychosocial stress induction experiment in which participants received both neutral (control condition) and negative (negative condition) comparative feedback after solving a challenging cognitive task. This study is the first to use a (non-actor) within-participant design that verifies a successful stress induction using both self-report (i.e., decreased reported valence) and physiological measures (i.e., increased heart rate acceleration using event-related cardiac responses during feedback exposure). Analyses of acoustic speech features showed a significant increase in Fundamental Frequency (F0) and Harmonics-to-Noise Ratio (HNR), and a significant decrease in shimmer during the negative feedback condition. Our results using read-out-loud speech comply with earlier research, yet we are the first to validate these results in a well-controlled but ecologically-valid setting to guarantee the generalization of our findings to real-life settings. Further research should aim to replicate these results in a free speech setting to test the robustness of our findings for real-world settings and should include semantics to also take into account what you say and not only how you say it.
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- 2022
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31. Niobium K‑Edge X‑ray Absorption Spectroscopy of Doped TiO2 Produced from Ilmenite Digested in Hydrochloric Acid
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Richard G. Haverkamp, Peter Kappen, Katie H. Sizeland, and Kia S. Wallwork
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Chemistry ,QD1-999 - Published
- 2022
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32. Music to prevent deliriUm during neuroSurgerY (MUSYC): a single-centre, prospective randomised controlled trial
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Marten J Poley, Robert-Jan Osse, Johannes Jeekel, M Klimek, Bronno van der Holt, Arnaud J P E Vincent, Clemens M F Dirven, Michiel Coesmans, Pablo R Kappen, M I Mos, Steven A Kushner, and Mathijs S van Schie
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Medicine - Abstract
Objectives Delirium is a serious complication following neurosurgical procedures. We hypothesise that the beneficial effect of music on a combination of delirium-eliciting factors might reduce delirium incidence following neurosurgery and subsequently improve clinical outcomes.Design Prospective randomised controlled trial.Setting Single centre, conducted at the neurosurgical department of the Erasmus Medical Center, Rotterdam, the Netherlands.Participants Adult patients undergoing craniotomy were eligible.Interventions Patients in the intervention group received preferred recorded music before, during and after the operation until day 3 after surgery. Patients in the control group were treated according to standard of clinical care.Primary and secondary outcome measures Primary outcome was presence or absence of postoperative delirium within the first 5 postoperative days measured with the Delirium Observation Screening Scale (DOSS) and, in case of a daily mean score of 3 or higher, a psychiatric evaluation with the latest Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Secondary outcomes included anxiety, heart rate variability (HRV), depth of anaesthesia, delirium severity and duration, postoperative complications, length of stay and location of discharge.Results We enrolled 189 patients (music=95, control=94) from July 2020 through September 2021. Delirium, as assessed by the DOSS, was less common in the music (n=11, 11.6%) than in the control group (n=21, 22.3%, OR:0.49, p=0.048). However, after DSM-5 confirmation, differences in delirium were not significant (4.2% vs 7.4%, OR:0.47, p=0.342). Moreover, music increased the HRV (root mean square of successive differences between normal heartbeats, p=0.012). All other secondary outcomes were not different between groups.Conclusion Our results support the efficacy of music in reducing the incidence of delirium after craniotomy, as found with DOSS but not after DSM-5 confirmation, substantiated by the effect of music on preoperative autonomic tone. Delirium screening tools should be validated and the long-term implications should be evaluated after craniotomy.Trial registration number Trialregister.nl: NL8503 and ClinicalTrials.gov: NCT04649450.
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- 2023
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33. Continuous Data-Driven Monitoring in Critical Congenital Heart Disease: Clinical Deterioration Model Development
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Ruben S Zoodsma, Rian Bosch, Thomas Alderliesten, Casper W Bollen, Teus H Kappen, Erik Koomen, Arno Siebes, and Joppe Nijman
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundCritical congenital heart disease (cCHD)—requiring cardiac intervention in the first year of life for survival—occurs globally in 2-3 of every 1000 live births. In the critical perioperative period, intensive multimodal monitoring at a pediatric intensive care unit (PICU) is warranted, as their organs—especially the brain—may be severely injured due to hemodynamic and respiratory events. These 24/7 clinical data streams yield large quantities of high-frequency data, which are challenging in terms of interpretation due to the varying and dynamic physiology innate to cCHD. Through advanced data science algorithms, these dynamic data can be condensed into comprehensible information, reducing the cognitive load on the medical team and providing data-driven monitoring support through automated detection of clinical deterioration, which may facilitate timely intervention. ObjectiveThis study aimed to develop a clinical deterioration detection algorithm for PICU patients with cCHD. MethodsRetrospectively, synchronous per-second data of cerebral regional oxygen saturation (rSO2) and 4 vital parameters (respiratory rate, heart rate, oxygen saturation, and invasive mean blood pressure) in neonates with cCHD admitted to the University Medical Center Utrecht, the Netherlands, between 2002 and 2018 were extracted. Patients were stratified based on mean oxygen saturation during admission to account for physiological differences between acyanotic and cyanotic cCHD. Each subset was used to train our algorithm in classifying data as either stable, unstable, or sensor dysfunction. The algorithm was designed to detect combinations of parameters abnormal to the stratified subpopulation and significant deviations from the patient’s unique baseline, which were further analyzed to distinguish clinical improvement from deterioration. Novel data were used for testing, visualized in detail, and internally validated by pediatric intensivists. ResultsA retrospective query yielded 4600 hours and 209 hours of per-second data in 78 and 10 neonates for, respectively, training and testing purposes. During testing, stable episodes occurred 153 times, of which 134 (88%) were correctly detected. Unstable episodes were correctly noted in 46 of 57 (81%) observed episodes. Twelve expert-confirmed unstable episodes were missed in testing. Time-percentual accuracy was 93% and 77% for, respectively, stable and unstable episodes. A total of 138 sensorial dysfunctions were detected, of which 130 (94%) were correct. ConclusionsIn this proof-of-concept study, a clinical deterioration detection algorithm was developed and retrospectively evaluated to classify clinical stability and instability, achieving reasonable performance considering the heterogeneous population of neonates with cCHD. Combined analysis of baseline (ie, patient-specific) deviations and simultaneous parameter-shifting (ie, population-specific) proofs would be promising with respect to enhancing applicability to heterogeneous critically ill pediatric populations. After prospective validation, the current—and comparable—models may, in the future, be used in the automated detection of clinical deterioration and eventually provide data-driven monitoring support to the medical team, allowing for timely intervention.
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- 2023
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34. Speech as an indicator for psychosocial stress: A network analytic approach
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Kappen, Mitchel, Hoorelbeke, Kristof, Madhu, Nilesh, Demuynck, Kris, and Vanderhasselt, Marie-Anne
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- 2022
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35. Atom-by-atom construction of attractors in a tunable finite size spin array
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Kolmus, Alex, Katsnelson, Mikhail I., Khajetoorians, Alexander A., and Kappen, Hilbert J.
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Condensed Matter - Statistical Mechanics ,Condensed Matter - Disordered Systems and Neural Networks ,Condensed Matter - Mesoscale and Nanoscale Physics - Abstract
We demonstrate that a two-dimensional finite and periodic array of Ising spins coupled via RKKY-like exchange can exhibit tunable magnetic states ranging from three distinct magnetic regimes: (1) a conventional ferromagnetic regime, (2) a glass-like regime, and (3) a new multi-well regime. These magnetic regimes can be tuned by one gate-like parameter, namely the ratio between the lattice constant and the oscillating interaction wavelength. We characterize the various magnetic regimes, quantifying the distribution of low energy states, aging relaxation dynamics, and scaling behavior. The glassy and multi-well behavior results from the competing character of the oscillating long-range exchange interactions. The multi-well structure features multiple attractors, each with a sizable basin of attraction. This may open the possible application of such atomic arrays as associative memories.
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- 2018
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36. Learning quantum models from quantum or classical data
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Kappen, Hilbert J
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Quantum Physics - Abstract
In this paper, we address the problem how to represent a classical data distribution in a quantum system. The proposed method is to learn quantum Hamiltonian that is such that its ground state approximates the given classical distribution. We review previous work on the quantum Boltzmann machine (QBM) and how it can be used to infer quantum Hamiltonians from quantum statistics. We then show how the proposed quantum learning formalism can also be applied to a purely classical data analysis. Representing the data as a rank one density matrix introduces quantum statistics for classical data in addition to the classical statistics. We show that quantum learning yields results that can be significantly more accurate than the classical maximum likelihood approach, both for unsupervised learning and for classification. The data density matrix and the QBM solution show entanglement, quantified by the quantum mutual information $I$. The classical mutual information in the data $I_c\le I/2=C$, with $C$ maximal classical correlations obtained by choosing a suitable orthogonal measurement basis. We suggest that the remaining mutual information $Q=I/2$ is obtained by non orthogonal measurements that may violate the Bell inequality. The excess mutual information $I-I_c$ may potentially be used to improve the performance of quantum implementations of machine learning or other statistical methods., Comment: 28 pages, 7 figures
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- 2018
37. Nonlinear Deconvolution by Sampling Biophysically Plausible Hemodynamic Models
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Ruiz-Euler, Hans-Christian, Marques, Jose R. Ferreira, and Kappen, Hilbert J.
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Quantitative Biology - Neurons and Cognition ,Physics - Data Analysis, Statistics and Probability - Abstract
Non-invasive methods to measure brain activity are important to understand cognitive processes in the human brain. A prominent example is functional magnetic resonance imaging (fMRI), which is a noisy measurement of a delayed signal that depends non-linearly on the neuronal activity through the neurovascular coupling. These characteristics make the inference of neuronal activity from fMRI a difficult but important step in fMRI studies that require information at the neuronal level. In this article, we address this inference problem using a Bayesian approach where we model the latent neural activity as a stochastic process and assume that the observed BOLD signal results from a realistic physiological (Balloon) model. We apply a recently developed smoothing method called APIS to efficiently sample the posterior given single event fMRI time series. To infer neuronal signals with high likelihood for multiple time series efficiently, a modification of the original algorithm is introduced. We demonstrate that our adaptive procedure is able to compensate the lacking of inputs in the model to infer the neuronal activity and that it outperforms dramatically the standard bootstrap particle filter-smoother in this setting. This makes the proposed procedure especially attractive to deconvolve resting state fMRI data. To validate the method, we evaluate the quality of the signals inferred using the timing information contained in them. APIS obtains reliable event timing estimates based on fMRI data gathered during a reaction time experiment with short stimuli. Hence, we show for the first time that one can obtain accurate absolute timing of neuronal activity by reconstructing the latent neural signal.
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- 2018
38. Consistent Adaptive Multiple Importance Sampling and Controlled Diffusions
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Thijssen, Sep and Kappen, H. J.
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Mathematics - Optimization and Control - Abstract
Recent progress has been made with Adaptive Multiple Importance Sampling (AMIS) methods that show improvement in effective sample size. However, consistency for the AMIS estimator has only been established in very restricted cases. Furthermore, the high computational complexity of the re-weighting in AMIS (called balance heuristic) makes it expensive for applications involving diffusion processes. In this work we consider sequential and adaptive importance sampling that is particularly suitable for diffusion processes. We propose a new discarding-re-weighting scheme that is of lower computational complexity, and we prove that the resulting AMIS is consistent. Using numerical experiments, we demonstrate that discarding-re-weighting performs very similar to the balance heuristic, but at a fraction of the computational cost.
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- 2018
39. Effective Connectivity from Single Trial fMRI Data by Sampling Biologically Plausible Models
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Ruiz-Euler, H. C. and Kappen, H. J.
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Quantitative Biology - Neurons and Cognition ,Physics - Data Analysis, Statistics and Probability - Abstract
The estimation of causal network architectures in the brain is fundamental for understanding cognitive information processes. However, access to the dynamic processes underlying cognition is limited to indirect measurements of the hidden neuronal activity, for instance through fMRI data. Thus, estimating the network structure of the underlying process is challenging. In this article, we embed an adaptive importance sampler called Adaptive Path Integral Smoother (APIS) into the Expectation-Maximization algorithm to obtain point estimates of causal connectivity. We demonstrate on synthetic data that this procedure finds not only the correct network structure but also the direction of effective connections from random initializations of the connectivity matrix. In addition--motivated by contradictory claims in the literature--we examine the effect of the neuronal timescale on the sensitivity of the BOLD signal to changes in the connectivity and on the maximum likelihood solutions of the connectivity. We conclude with two warnings: First, the connectivity estimates under the assumption of slow dynamics can be extremely biased if the data was generated by fast neuronal processes. Second, the faster the time scale, the less sensitive the BOLD signal is to changes in the incoming connections to a node. Hence, connectivity estimation using realistic neural dynamics timescale requires extremely high-quality data and seems infeasible in many practical data sets.
- Published
- 2018
40. On the role of synaptic stochasticity in training low-precision neural networks
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Baldassi, Carlo, Gerace, Federica, Kappen, Hilbert J., Lucibello, Carlo, Saglietti, Luca, Tartaglione, Enzo, and Zecchina, Riccardo
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Condensed Matter - Disordered Systems and Neural Networks ,Computer Science - Machine Learning ,Computer Science - Neural and Evolutionary Computing ,Statistics - Machine Learning - Abstract
Stochasticity and limited precision of synaptic weights in neural network models are key aspects of both biological and hardware modeling of learning processes. Here we show that a neural network model with stochastic binary weights naturally gives prominence to exponentially rare dense regions of solutions with a number of desirable properties such as robustness and good generalization performance, while typical solutions are isolated and hard to find. Binary solutions of the standard perceptron problem are obtained from a simple gradient descent procedure on a set of real values parametrizing a probability distribution over the binary synapses. Both analytical and numerical results are presented. An algorithmic extension aimed at training discrete deep neural networks is also investigated., Comment: 7 pages + 14 pages of supplementary material
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- 2017
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41. Invited Discussion on “Comparison of Effectiveness and Safety of a Botulinum Toxin Mono Therapy and a Combination Therapy with Hyaluronic Acid Filler for Improving Glabellar Frown”
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Hodgkinson, Darryl J. and Kappen, Isabelle F. P. M.
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- 2022
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42. Aberrant lipid accumulation in the mouse visceral yolk sac resulting from maternal diabetes and obesity
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Man Zhang, J. Michael Salbaum, Sydney Jones, David Burk, and Claudia Kappen
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lipid droplet ,lipid transporter ,lipid deficiency ,neural tube defect ,hyperglycemic ,hyperlipidemia ,Biology (General) ,QH301-705.5 - Abstract
Maternal diabetes and obesity in pregnancy are well-known risk factors for structural birth defects, including neural tube defects and congenital heart defects. Progeny from affected pregnancies are also predisposed to developing cardiometabolic disease in later life. Based upon in vitro embryo cultures of rat embryos, it was postulated that nutrient uptake by the yolk sac is deficient in diabetic pregnancies. In contrast, using two independent mouse models of maternal diabetes, and a high-fat diet-feeding model of maternal obesity, we observed excessive lipid accumulation at 8.5 days in the yolk sac. The numbers as well as sizes of intracellular lipid droplets were increased in yolk sacs of embryos from diabetic and obese pregnancies. Maternal metabolic disease did not affect expression of lipid transporter proteins, including ApoA1, ApoB and SR-B1, consistent with our earlier report that expression of glucose and fatty acid transporter genes was also unchanged in diabetic pregnancy-derived yolk sacs. Colocalization of lipid droplets with lysosomes was significantly reduced in the yolk sacs from diabetic and obese pregnancies compared to yolk sacs from normal pregnancies. We therefore conclude that processing of lipids is defective in pregnancies affected by maternal metabolic disease, which may lead to reduced availability of lipids to the developing embryo. The possible implications of insufficient supply of lipids -and potentially of other nutrients-to the embryos experiencing adverse pregnancy conditions are discussed.
- Published
- 2023
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43. The effect of musicality on language recovery after awake glioma surgery
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Pablo R. Kappen, Jan van den Brink, Johannes Jeekel, Clemens M. F. Dirven, Markus Klimek, Marike Donders-Kamphuis, Christa S. Docter-Kerkhof, Saskia A. Mooijman, Ellen Collee, Rishi D. S. Nandoe Tewarie, Marike L. D. Broekman, Marion Smits, Arnaud J. P. E. Vincent, and Djaina Satoer
- Subjects
music ,neuro-oncology ,neuroplasticity ,corpus callosum ,aphasia ,brain tumors ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
IntroductionAwake craniotomy is increasingly used to resect intrinsic brain tumors while preserving language. The level of musical training might affect the speed and extend of postoperative language recovery, as increased white matter connectivity in the corpus callosum is described in musicians compared to non-musicians.MethodsIn this cohort study, we included adult patients undergoing treatment for glioma with an awake resection procedure at two neurosurgical centers and assessed language preoperatively (T1) and postoperatively at three months (T2) and one year (T3) with the Diagnostic Instrument for Mild Aphasia (DIMA), transferred to z-scores. Moreover, patients’ musicality was divided into three groups based on the Musical Expertise Criterion (MEC) and automated volumetric measures of the corpus callosum were conducted.ResultsWe enrolled forty-six patients, between June 2015 and September 2021, and divided in: group A (non-musicians, n = 19, 41.3%), group B (amateur musicians, n = 17, 36.9%) and group C (trained musicians, n = 10, 21.7%). No significant differences on postoperative language course between the three musicality groups were observed in the main analyses. However, a trend towards less deterioration of language (mean/SD z-scores) was observed within the first three months on the phonological domain (A: −0.425/0.951 vs. B: −0.00100/1.14 vs. C: 0.0289/0.566, p-value = 0.19) with a significant effect between non-musicians vs. instrumentalists (A: −0.425/0.951 vs. B + C: 0.201/0.699, p = 0.04). Moreover, a non-significant trend towards a larger volume (mean/SD cm3) of the corpus callosum was observed between the three musicality groups (A: 6.67/1.35 vs. B: 7.09/1.07 vs. C: 8.30/2.30, p = 0.13), with the largest difference of size in the anterior corpus callosum in non-musicians compared to trained musicians (A: 3.28/0.621 vs. C: 4.90/1.41, p = 0.02).ConclusionWith first study on this topic, we support that musicality contributes to language recovery after awake glioma surgery, possibly attributed to a higher white matter connectivity at the anterior part of the corpus callosum. Our conclusion should be handled with caution and interpreted as hypothesis generating only, as most of our results were not significant. Future studies with larger sample sizes are needed to confirm our hypothesis.
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- 2023
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44. Delirium in neurosurgery: a systematic review and meta-analysis
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Kappen, P. R., Kakar, E., Dirven, C. M. F., van der Jagt, M., Klimek, M., Osse, R. J., and Vincent, A. P. J. E.
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- 2022
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45. STOP: an open label crossover trial to study ICS withdrawal in patients with a combination of obesity and low-inflammatory asthma and evaluate its effect on asthma control and quality of life
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Witte, Jan A., Braunstahl, Gert-Jan, Blox, Wouter J. B., van ’t Westeinde, Susan C., in ’t Veen, Johannes C. C. M., Kappen, Jasper H., and van Rossum, Elisabeth F. C.
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- 2022
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46. Author Correction: Novel mode of defective neural tube closure in the non-obese diabetic (NOD) mouse strain
- Author
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Salbaum, J. Michael, Kruger, Claudia, MacGowan, Jacalyn, Herion, Nils J., Burk, David, and Kappen, Claudia
- Published
- 2022
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47. Acoustic speech features in social comparison: how stress impacts the way you sound
- Author
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Kappen, Mitchel, van der Donckt, Jonas, Vanhollebeke, Gert, Allaert, Jens, Degraeve, Vic, Madhu, Nilesh, Van Hoecke, Sofie, and Vanderhasselt, Marie-Anne
- Published
- 2022
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48. STOP: an open label crossover trial to study ICS withdrawal in patients with a combination of obesity and low-inflammatory asthma and evaluate its effect on asthma control and quality of life
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Jan A. Witte, Gert-Jan Braunstahl, Wouter J. B. Blox, Susan C. van ’t Westeinde, Johannes C. C. M. in ’t Veen, Jasper H. Kappen, and Elisabeth F. C. van Rossum
- Subjects
Asthma ,Obesity ,T2-low ,Corticosteroids ,ICS tapering ,RCT ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Asthma patients with obesity often have a high disease burden, despite the use of high-dose inhaled corticosteroids (ICS). In contrast to asthmatics with normal weight, the efficacy of ICS in patients with obesity and asthma is often relatively low. Meanwhile, patients do suffer from side effects, such as weight gain, development of diabetes, cataract, or high blood pressure. The relatively poor response to ICS might be explained by the low prevalence of type 2 inflammatory patterns (T2-low) in patients with asthma and obesity. T2-low inflammation is characterized by low eosinophilic count, low Fractional exhaled NO (FeNO), no clinically allergy-driven asthma, and no need for maintenance oral corticosteroids (OCS). We aim to study whether ICS can be safely withdrawn in patients with T2-low asthma and obesity while maintaining an equal level of asthma control. Secondary outcomes focus on the prevalence of ‘false-negative’ T2-low phenotypes (i.e. T2-hidden) and the effect of ICS withdrawal on parameters of the metabolic syndrome. This study will lead to a better understanding of this poorly understood subgroup and might find new treatable traits. Methods The STOP trial is an investigator-initiated, multicenter, non-inferiority, open-label, crossover study aiming to assess whether ICS can be safely withdrawn in adults aged 17–75 years with T2-low asthma and obesity (body mass index (BMI) ≥ 30 kg/m2). Patients will be randomly divided into two arms (both n = 60). One arm will start with fixed-dose ICS (control group) and one arm will taper and subsequently stop ICS (intervention group). Patients in the intervention group will remain ICS naïve for ten weeks. After a washout of 4 weeks, patients will crossover to the other study arm. The crossover study takes 36 weeks to complete. Patients will be asked to participate in the extension study, to investigate the long-term metabolic benefits of ICS withdrawal. Discussion This study yields valuable data on ICS tapering in patients with T2-low asthma and obesity. It informs future guidelines and committees on corticosteroid-sparing algorithms in these patients. Trial registration Netherlands Trial Register, NL8759, registered 2020–07-06, https://www.trialregister.nl/trial/8759 . Protocol version and date: version 2.1, 20 November 2020.
- Published
- 2022
- Full Text
- View/download PDF
49. Efficient Optical flow and Stereo Vision for Velocity Estimation and Obstacle Avoidance on an Autonomous Pocket Drone
- Author
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McGuire, Kimberly, de Croon, Guido, De Wagter, Christophe, Tuyls, Karl, and Kappen, Hilbert
- Subjects
Computer Science - Robotics - Abstract
Miniature Micro Aerial Vehicles (MAV) are very suitable for flying in indoor environments, but autonomous navigation is challenging due to their strict hardware limitations. This paper presents a highly efficient computer vision algorithm called Edge-FS for the determination of velocity and depth. It runs at 20 Hz on a 4 g stereo camera with an embedded STM32F4 microprocessor (168 MHz, 192 kB) and uses feature histograms to calculate optical flow and stereo disparity. The stereo-based distance estimates are used to scale the optical flow in order to retrieve the drone's velocity. The velocity and depth measurements are used for fully autonomous flight of a 40 g pocket drone only relying on on-board sensors. The method allows the MAV to control its velocity and avoid obstacles., Comment: 7 pages, 10 figures, Published at IEEE Robotics and Automation Letters
- Published
- 2016
- Full Text
- View/download PDF
50. Broad spectrum of CRISPR-induced edits in an embryonic lethal gene
- Author
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Kayla T. B. Fuselier, J. Michael Salbaum, and Claudia Kappen
- Subjects
Medicine ,Science - Abstract
Abstract Mendelian genetics poses practical limitations on the number of mutant genes that can be investigated simultaneously for their roles in embryonic development in the mouse. While CRISPR-based gene editing of multiple genes at once offers an attractive alternative strategy, subsequent breeding or establishment of permanent mouse lines will rapidly segregate the different mutant loci again. Direct phenotypic analysis of genomic edits in an embryonic lethal gene in F0 generation mice, or F0 mouse embryos, circumvents the need for breeding or establishment of mutant mouse lines. In the course of genotyping a large cohort of F0 CRISPants, where the embryonic lethal gene T/brachyury was targeted, we noted the presence of multiple CRISPR-induced modifications in individual embryos. Using long-read single-molecule Nanopore sequencing, we identified a wide variety of deletions, ranging up to 3 kb, that would not have been detected or scored as wildtype with commonly used genotyping methods that rely on subcloning and short-read or Sanger sequencing. Long-read sequencing results were crucial for accurate genotype–phenotype correlation in our F0 CRISPants. We thus demonstrate feasibility of screening manipulated F0 embryos for mid-gestation phenotypic consequences of CRISPR-induced mutations without requiring derivation of permanent mouse lines.
- Published
- 2021
- Full Text
- View/download PDF
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