Swiss national guideline for reimbursement of enzyme replacement therapy in late-onset Pompe disease.

Glycogen storage disease type II is a rare multi-systemic disorder characterised by an intracellular accumulation of glycogen due a mutation in the acid alpha glucosidase (GAA) gene. The level of residual enzyme activity, the genotype and other yet unknown factors account for the broad variation of the clinical phenotype. The classical infantile form is characterised by severe muscle hypotonia and cardiomyopathy leading to early death. The late-onset form presents as a limb girdle myopathy with or without pulmonary dysfunction. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) in infants is life saving. In contrast, therapeutic efficacy of rhGAA in the late-onset form is modest. High expenses of rhGAA, on-going infusions and poor pharmacokinetic efficacy raised a discussion of the cost effectiveness of ERT in late-onset Pompe disease in Switzerland. This discussion was triggered by a Swiss federal court ruling which confirmed the reluctance of a health care insurer not to reimburse treatment costs in a 67-year-old female suffering from Pompe disease. As a consequence of this judgement ERT was stopped by all insurance companies in late-onset Pompe patients in Switzerland regardless of their clinical condition. Subsequent negotiations lead to the release of a national guideline of the management of late-onset Pompe disease. Initiation and limitation of ERT is outlined in a national Pompe registry. Reimbursement criteria are defined and individual efficacy of ERT with rhGAA is continuously monitored.

The emotional power of music: How music enhances the feeling of affective pictures

Music is an intriguing stimulus widely used in movies to increase the emotional experience. However, no brain imaging study has to date examined this enhancement effect using emotional pictures (the modality mostly used in emotion research) and musical excerpts. Therefore, we designed this functional magnetic resonance imaging study to explore how musical stimuli enhance the feeling of affective pictures. In a classical block design carefully controlling for habituation and order effects, we presented fearful and sad pictures (mostly taken from the IAPS) either alone or combined with congruent emotional musical excerpts (classical pieces). Subjective ratings clearly indicated that the emotional experience was markedly increased in the combined relative to the picture condition. Furthermore, using a second-level analysis and regions of interest approach, we observed a clear functional and structural dissociation between the combined and the picture condition. Besides increased activation in brain areas known to be involved in auditory as well as in neutral and emotional visual-auditory integration processes, the combined condition showed increased activation in many structures known to be involved in emotion processing (including for example amygdala, hippocampus, parahippocampus, insula, striatum, medial ventral frontal cortex, cerebellum, fusiform gyrus). In contrast, the picture condition only showed an activation increase in the cognitive part of the prefrontal cortex, mainly in the right dorsolateral prefrontal cortex. Based on these findings, we suggest that emotional pictures evoke a more cognitive mode of emotion perception, whereas congruent presentations of emotional visual and musical stimuli rather automatically evoke strong emotional feelings and experiences.

The neural circuitry of a broken promise

Promises are one of the oldest human-specific psychological mechanisms fostering cooperation and trust. Here, we study the neural underpinnings of promise keeping and promise breaking. Subjects first make a promise decision (promise stage), then they anticipate whether the promise affects the interaction partner's decision (anticipation stage) and are subsequently free to keep or break the promise (decision stage). Findings revealed that the breaking of the promise is associated with increased activation in the DLPFC, ACC, and amygdala, suggesting that the dishonest act involves an emotional conflict due to the suppression of the honest response. Moreover, the breach of the promise can be predicted by a perfidious brain activity pattern (anterior insula, ACC, inferior frontal gyrus) during the promise and anticipation stage, indicating that brain measurements may reveal malevolent intentions before dishonest or deceitful acts are actually committed.

A Conceptual Model to Combine Creativity Techniques with Fuzzy Cognitive Maps for Enhanced Knowledge Management

This chapter introduces a conceptual model to combine creativity techniques with fuzzy cognitive maps (FCMs) and aims to support knowledge management methods by improving expert knowledge acquisition and aggregation. The aim of the conceptual model is to represent acquired knowledge in a manner that is as computer-understandable as possible with the intention of developing automated reasoning in the future as part of intelligent information systems. The formal represented knowledge thus may provide businesses with intelligent information integration. To this end, we introduce and evaluate various creativity techniques with a list of attributes to define the most suitable to combine with FCMs. This proposed combination enables enhanced knowledge management through the acquisition and representation of expert knowledge with FCMs. Our evaluation indicates that the creativity technique known as mind mapping is the most suitable technique in our set. Finally, a scenario from stakeholder management demonstrates the combination of mind mapping with FCMs as an integrated system.

Choosing the Path of Austerity: How Policy Coalitions Shape Welfare-policy Choices in Periods of Fiscal Consolidation

In general, fiscal adjustments are associated with significant reductions in social spending. Hence, the welfare state is not spared from austerity. Because the welfare state is still central to party competition, this is electorally risky. The paper addresses the following questions: Do left parties differ from their centrist and rightist competitors in the design of austerity measures? And does government type has an impact on the extent to which austerity policies rely on social spending cuts? By comparing 17 OECD countries between 1982 and 2009 we show that if governments embark on a path to austerity, their ideology does not have a significant effect on the magnitude of welfare state retrenchment. However, if major opposition parties and interest groups rally against social spending cuts, a broad pro-reform coalition is a crucial precondition for large fiscal consolidation programs to rely on substantial cuts to social security.

Politische Voraussetzungen von Austeritätspolitik: Ein internationaler Vergleich von 17 etablierten Demokratien zwischen 1978 und 2009

Welche politischen Voraussetzungen müssen gegeben sein, damit Regierungen den Staatshaushalt konsolidieren? In diesem Beitrag konzentrieren wir uns auf zwei Erklärungsgrößen: Die parteipolitische Zusammensetzung einer Regierung und die Breite der Regierungskoalition. Wir zeigen einerseits, dass die Wahrscheinlichkeit der Initiierung eines Konsolidierungsprogramms unter Parteien der politischen Rechten sowie unter kleinen Reformkoalitionen (Einparteienregierungen und minimal winning Koalitionen) am höchsten ist. Andererseits finden wir ein nahezu entgegengesetztes Muster bezüglich des Umfangs der verabschiedeten Sparmaßnahmen. Hier zeigt sich, dass die Breite der Regierungskoalition grundsätzlich einen positiven Einfluss auf die Größe des Konsolidierungsprogramms ausübt. Zudem fallen die Sparpakete rechter Parteien generell bescheidener aus als jene ihrer Konkurrenten der politischen Mitte und Linken. Wir erklären diese Ergebnisse mit den strategischen und wahlpolitischen Optionen der Akteure, auf Basis eines Vergleichs von 17 OECD-Ländern zwischen 1978 und 2009.

Effect of irradiation distance on image contrast in epi-optoacoustic imaging of human volunteers

In combined clinical optoacoustic (OA) and ultrasound (US) imaging, epi-mode irradiation and detection integrated into one single probe offers flexible imaging of the human body. The imaging depth in epi-illumination is, however, strongly affected by clutter. As shown in previous phantom experiments, the location of irradiation plays an important role in clutter generation. We investigated the influence of the irradiation geometry on the local image contrast of clinical images, by varying the separation distance between the irradiated area and the acoustic imaging plane of a linear ultrasound transducer in an automated scanning setup. The results for different volunteers show that the image contrast can be enhanced on average by 25% and locally by more than a factor of two, when the irradiated area is slightly separated from the probe. Our findings have an important impact on the design of future optoacoustic probes for clinical application.

Computed Ultrasound Tomography in Echo mode (CUTE) of speed of sound for diagnosis and for aberration correction in pulse-echo sonography

Sound speed as a diagnostic marker for various diseases of human tissue has been of interest for a while. Up to now, mostly transmission ultrasound computed tomography (UCT) was able to detect spatially resolved sound speed, and its promise as a diagnostic tool has been demonstrated. However, UCT is limited to acoustically transparent samples such as the breast. We present a novel technique where spatially resolved detection of sound speed can be achieved using conventional pulse-echo equipment in reflection mode. For this purpose, pulse-echo images are acquired under various transmit beam directions and a two-dimensional map of the sound speed is reconstructed from the changing phase of local echoes using a direct reconstruction method. Phantom results demonstrate that a high spatial resolution (1 mm) and contrast (0.5 % of average sound speed) can be achieved suitable for diagnostic purposes. In comparison to previous reflection-mode based methods, CUTE works also in a situation with only diffuse echoes, and its direct reconstruction algorithm enables real-time application. This makes it suitable as an addition to conventional clinical ultrasound where it has the potential to benefit diagnosis in a multimodal approach. In addition, knowledge of the spatial distribution of sound speed allows full aberration correction and thus improved spatial resolution and contrast of conventional B-mode ultrasound. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.