The purpose of this study was to determine the impact of vagal nerve stimulation (VNS) on the vocal quality using the dysphonia severity index (DSI). It was hypothesized that the objective vocal quality and other vocal characteristics are disordered in comparison with an age- and gender-matched control group. In addition, the acoustic vocal parameters were compared during three conditions: at rest, during normal stimulation, and raised stimulation. A significant relation between the amount of stimulation and the presence of disturbed acoustic parameters was hypothesized.Subjective (auditory-perceptual evaluation and voice handicap index) and objective (aerodynamic, vocal range, acoustic measurements and determination of the DSI) measurements were used to determine the vocal quality in 13 subjects with VNS in three different conditions (at rest and during normal and raised stimulation) and the age- and gender-matched control group.The subjects with VNS had a disordered perceptual vocal quality mainly characterized by the presence of a moderate roughness and slight breathiness, and the objective vocal quality by means of the DSI value is -2.4. During stimulation and especially during raised stimulation, the fundamental frequency is significantly increased. However, the subjects experienced no psychosocial handicapping effect of the vocal quality on the quality of life.Subjects with VNS have typical vocal characteristics. Ear, nose, and throat specialists and voice therapist must be aware of the presence of this vocal pattern at rest and during normal and raised stimulation. Especially, professional voice users and elite vocal performers must be informed before implantation.
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The user’s experience with a recommender system is significantly shaped by the dynamics of user-algorithm interactions. These interactions are often evaluated using interaction qualities, such as controllability, trust, and autonomy, to gauge their impact. As part of our effort to systematically categorize these evaluations, we explored the suitability of the interaction qualities framework as proposed by Lenz, Dieffenbach and Hassenzahl. During this examination, we uncovered four challenges within the framework itself, and an additional external challenge. In studies examining the interaction between user control options and interaction qualities, interdependencies between concepts, inconsistent terminology, and the entity perspective (is it a user’s trust or a system’s trustworthiness) often hinder a systematic inventory of the findings. Additionally, our discussion underscored the crucial role of the decision context in evaluating the relation of algorithmic affordances and interaction qualities. We propose dimensions of decision contexts (such as ‘reversibility of the decision’, or ‘time pressure’). They could aid in establishing a systematic three-way relationship between context attributes, attributes of user control mechanisms, and experiential goals, and as such they warrant further research. In sum, while the interaction qualities framework serves as a foundational structure for organizing research on evaluating the impact of algorithmic affordances, challenges related to interdependencies and context-specific influences remain. These challenges necessitate further investigation and subsequent refinement and expansion of the framework.
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Experts like Jouslin de Noray, Shiba and Hardjono discern three paradigms in quality management: control, continuous improvement and breakthrough. Van Kemenade argues that before being able to reach breakthrough you need another paradigm: commitment.
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Flying insects like dragonflies, flies, bumblebees are able to couple hovering ability with the ability for a quick transition to forward flight. Therefore, they inspire us to investigate the application of swarms of flapping-wing mini-drones in horticulture. The production and trading of agricultural/horticultural goods account for the 9% of the Dutch gross domestic product. A significant part of the horticultural products are grown in greenhouses whose extension is becoming larger year by year. Swarms of bio-inspired mini-drones can be used in applications such as monitoring and control: the analysis of the data collected enables the greenhouse growers to achieve the optimal conditions for the plants health and thus a high productivity. Moreover, the bio-inspired mini-drones can detect eventual pest onset at plant level that leads to a strong reduction of chemicals utilization and an improvement of the food quality. The realization of these mini-drones is a multidisciplinary challenge as it requires a cross-domain collaboration between biologists, entomologists and engineers with expertise in robotics, mechanics, aerodynamics, electronics, etc. Moreover a co-creation based collaboration will be established with all the stakeholders involved. With this approach we can integrate technical and social-economic aspects and facilitate the adoption of this new technology that will make the Dutch horticulture industry more resilient and sustainable.
Cell-based production processes in bioreactors and fermenters need to be carefully monitored due to the complexity of the biological systems and the growth processes of the cells. Critical parameters are identified and monitored over time to guarantee product quality and consistency and to minimize over-processing and batch rejections. Sensors are already available for monitoring parameters such as temperature, glucose, pH, and CO2, but not yet for low-concentration substances like proteins and nucleic acids (DNA). An interesting critical parameter to monitor is host cell DNA (HCD), as it is considered an impurity in the final product (downstream process) and its concentration indicates the cell status (upstream process). The Molecular Biosensing group at the Eindhoven University of Technology and Helia Biomonitoring are developing a sensor for continuous biomarker monitoring, based on Biosensing by Particle Motion. With this consortium, we want to explore whether the sensor is suitable for the continuous measurement of HCD. Therefore, we need to set-up a joint laboratory infrastructure to develop HCD assays. Knowledge of how cells respond to environmental changes and how this is reflected in the DNA concentration profile in the cell medium needs to be explored. This KIEM study will enable us to set the first steps towards continuous HCD sensing from cell culture conditions controlling cell production processes. It eventually generates input for machine learning to be able to automate processes in bioreactors and fermenters e.g. for the production of biopharmaceuticals. The project entails collaboration with new partners and will set a strong basis for subsequent research projects leading to scientific and economic growth, and will also contribute to the human capital agenda.
Huntington’s disease (HD) and various spinocerebellar ataxias (SCA) are autosomal dominantly inherited neurodegenerative disorders caused by a CAG repeat expansion in the disease-related gene1. The impact of HD and SCA on families and individuals is enormous and far reaching, as patients typically display first symptoms during midlife. HD is characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. SCAs are mainly characterized by ataxia but also other symptoms including cognitive deficits, similarly affecting quality of life and leading to disability. These problems worsen as the disease progresses and affected individuals are no longer able to work, drive, or care for themselves. It places an enormous burden on their family and caregivers, and patients will require intensive nursing home care when disease progresses, and lifespan is reduced. Although the clinical and pathological phenotypes are distinct for each CAG repeat expansion disorder, it is thought that similar molecular mechanisms underlie the effect of expanded CAG repeats in different genes. The predicted Age of Onset (AO) for both HD, SCA1 and SCA3 (and 5 other CAG-repeat diseases) is based on the polyQ expansion, but the CAG/polyQ determines the AO only for 50% (see figure below). A large variety on AO is observed, especially for the most common range between 40 and 50 repeats11,12. Large differences in onset, especially in the range 40-50 CAGs not only imply that current individual predictions for AO are imprecise (affecting important life decisions that patients need to make and also hampering assessment of potential onset-delaying intervention) but also do offer optimism that (patient-related) factors exist that can delay the onset of disease.To address both items, we need to generate a better model, based on patient-derived cells that generates parameters that not only mirror the CAG-repeat length dependency of these diseases, but that also better predicts inter-patient variations in disease susceptibility and effectiveness of interventions. Hereto, we will use a staggered project design as explained in 5.1, in which we first will determine which cellular and molecular determinants (referred to as landscapes) in isogenic iPSC models are associated with increased CAG repeat lengths using deep-learning algorithms (DLA) (WP1). Hereto, we will use a well characterized control cell line in which we modify the CAG repeat length in the endogenous ataxin-1, Ataxin-3 and Huntingtin gene from wildtype Q repeats to intermediate to adult onset and juvenile polyQ repeats. We will next expand the model with cells from the 3 (SCA1, SCA3, and HD) existing and new cohorts of early-onset, adult-onset and late-onset/intermediate repeat patients for which, besides accurate AO information, also clinical parameters (MRI scans, liquor markers etc) will be (made) available. This will be used for validation and to fine-tune the molecular landscapes (again using DLA) towards the best prediction of individual patient related clinical markers and AO (WP3). The same models and (most relevant) landscapes will also be used for evaluations of novel mutant protein lowering strategies as will emerge from WP4.This overall development process of landscape prediction is an iterative process that involves (a) data processing (WP5) (b) unsupervised data exploration and dimensionality reduction to find patterns in data and create “labels” for similarity and (c) development of data supervised Deep Learning (DL) models for landscape prediction based on the labels from previous step. Each iteration starts with data that is generated and deployed according to FAIR principles, and the developed deep learning system will be instrumental to connect these WPs. Insights in algorithm sensitivity from the predictive models will form the basis for discussion with field experts on the distinction and phenotypic consequences. While full development of accurate diagnostics might go beyond the timespan of the 5 year project, ideally our final landscapes can be used for new genetic counselling: when somebody is positive for the gene, can we use his/her cells, feed it into the generated cell-based model and better predict the AO and severity? While this will answer questions from clinicians and patient communities, it will also generate new ones, which is why we will study the ethical implications of such improved diagnostics in advance (WP6).
