Diagnostiek en herstelmeting van taalproblemen na niet-aangeboren hersenletsel

The main aim of the research reported in this thesis is to provide a practical contribution to the assessment of language problems in brain-damaged patients, e.g. patients suffering from the consequences of a stroke, traumatic brain damage or brain tumour. A broad clinical populations is studied, since apart from aphasics also right-brain-damaged (RBD) patients were included. In the latter case the main language problems are not confined to the linguistic levels of verbal behaviour as in aphasia, but affect the more cognitive and pragmatic aspects of communication. To put it another way, they spread from the level of language functions (phonology, syntaxis, word finding) to the level of participation. Existing Dutch tests for verbal behaviour (Aachen Aphasia Test, Boston Naming Test, Metaphor task) were evaluated and if necessary adjusted and elaborated in order to answer the specific questions that arose from the clinical setting. Besides the emphasis on the practical assessment of language problems we tried to solve a number of fundamental issues dealing with the communicative problems in RBD-patients and the role of the right hemi-sphere in normal language processing

Comparison of various guidance strategies to achieve time constraints in optimal descents

Continuous Descent Operations (CDOs) have been subject of extensive research in the last decades. Even if proving successful in reducing the environmental impact [1], such operations suffer from a well-known drawback: the loss of predictability from the Air Traffic Control (ATC) point of view, in terms of overfly-times at certain fixes along the route. Consequently, existing CDO implementations require ATC to introduce additional sequencing buffers to ensure safe separation among aircraft, thus reducing airport capacity. For all these reasons, in busy airports, CDOs are only feasible in off-peak hours, when the traffic demand is low [2]. In other to face this issue, several Air Traffic Management (ATM) concepts have been proposed that aim to enable CDOs also in high traffic demand scenarios. For instance, several works investigated the use of fixed Fight-Path-Angle (FPA) descents with time control to improve both spatial and temporal predictability [3, 4]. The disadvantage of fixed FPA descents is that predictability is achieved at the cost of thrust settings that might be different from idle. Another potential approach to enable CDOs in dense traffic scenarios consists of assigning controlled times of arrival (CTAs) to each aircraft at some strategic fixes for separation, negotiation starts with the on-board computation of the earliest and latest achievable times of arrival at the metering fix, and the subsequent down-link of this information to the ground automation system. Based on this feasible time window and the surrounding traffic a CTA is computed by a ground-based support tool, such as an arrival manager. Then, the incoming CTA is entered on-board as a Required Time of Arrival (RTA) into the FMS, and the on-board trajectory planner computes a new (optimal) trajectory plan starting at the current state, while satisfying the RTA and other operational constraints (e.g., altitude and speed constraints) [5].Peer ReviewedPostprint (author's final draft

Entanglement of Genetics and Epigenetics in Parkinson’s Disease

Parkinson disease (PD) is a common neurodegenerative disorder that progresses with age, with an increasing number of symptoms. Some of the efforts to understand PD progression have been focusing on the regulation of epigenetic mechanisms, that generally include small molecular modifications to the DNA and histones that are essential for regulating gene activity. Here, we have pointed out difficulties to untangle genetic and epigenetic mechanisms, and reviewed several studies that have aimed for untangling. Some of those have enabled more solid claims on independent roles for epigenetic mechanisms. Hereby, evidence that specific DNA hydroxymethylation, global hyperacetylation, and histone deacetylase (HDAC) dependent regulation of SNCA, one of the hallmark genes involved in PD, have become more prominent from the current perspective, than mechanisms that directly involve DNA methylation. In the absence of current epigenetic clinical targets to counteract PD progression, we also hypothesize how several mechanisms may affect local and global epigenetics in PD neurons, including inflammation, oxidative stress, autophagy and DNA repair mechanisms which may lead to future therapeutic targets

The effect of SSRIs on fear learning: a systematic review and meta-analysis

RATIONALE: Selective serotonin reuptake inhibitors (SSRIs) are considered first-line medication for anxiety-like disorders such as panic disorder, generalized anxiety disorder, and post-traumatic stress disorder. Fear learning plays an important role in the development and treatment of these disorders. Yet, the effect of SSRIs on fear learning are not well known. OBJECTIVE: We aimed to systematically review the effect of six clinically effective SSRIs on acquisition, expression, and extinction of cued and contextual conditioned fear. METHODS: We searched the Medline and Embase databases, which yielded 128 articles that met the inclusion criteria and reported on 9 human and 275 animal experiments. RESULTS: Meta-analysis showed that SSRIs significantly reduced contextual fear expression and facilitated extinction learning to cue. Bayesian-regularized meta-regression further suggested that chronic treatment exerts a stronger anxiolytic effect on cued fear expression than acute treatment. Type of SSRI, species, disease-induction model, and type of anxiety test used did not seem to moderate the effect of SSRIs. The number of studies was relatively small, the level of heterogeneity was high, and publication bias has likely occurred which may have resulted in an overestimation of the overall effect sizes. CONCLUSIONS: This review suggests that the efficacy of SSRIs may be related to their effects on contextual fear expression and extinction to cue, rather than fear acquisition. However, these effects of SSRIs may be due to a more general inhibition of fear-related emotions. Therefore, additional meta-analyses on the effects of SSRIs on unconditioned fear responses may provide further insight into the actions of SSRIs