Soll eine Präimplantationsdiagnostik eingesetzt werden dürfen?

Biowissenschaft und Technik verschaffen den Verfahren der artifiziellen Reproduktion immer weiteren Raum, der freilich rechtlicher Legitimation bedarf. Zur In-vitro-Fertilisation „mit ihren enormen Misserfolgsraten“ und zur Pränataldiagnostik „mit ihren gravierenden eugenischen Implikationen“ tritt – vor dem Hintergrund weithin preisgegebenen Schutzes des ungeborenen Lebens – die Präimplantationsdiagnostik, das heißt: die Embryonenselektion. Sie bringt die künstliche Befruchtung in einen anderen Zusammenhang als den vom Embryonenschutzgesetz gewollten. Im Unterschied zur Pränataldiagnostik setzt der Mediziner die Erzeugung eines menschlichen Embryos selbst ins Werk, um ihn im Falle eines pathologischen Befundes zu verwerfen. Es geht um ein biomedizinisches Verfahren, bei dem Entscheidungen über Leben und Tod anstehen, also um Fragen der Allgemeinheit und damit des Rechts. Richtlinien eines Berufsstandes können diesem Gegenstand keineswegs gerecht werden. Mit ihrem „Diskussionsentwurf zu einer Richtlinie zur Präimplantationsdiagnostik“ hat die Bundesärztekammer einen voreiligen und verfehlten Schritt getan. Die Präimplantations-diagnostik ist rechtlich nicht legitimiert. Ihr steht vielmehr das geltende Recht entgegen: das Grundgesetz, das Embryonenschutzgesetz und die Berufsordnung. Der Gesetzgeber sollte nicht in die Fortschrittsfalle gehen, die Entscheidung zwischen künstlich erzeugten erwünschten und unerwünschten Menschen nicht zum Programm werden lassen und am Ende auch der verbrauchenden Embryonenforschung nicht den Weg bereiten

Modelling large motion events in fMRI studies of patients with epilepsy

EEG-correlated fMRI can provide localisation information on the generators of epileptiform discharges in patients with focal epilepsy. To increase the technique's clinical potential, it is important to consider ways of optimising the yield of each experiment while minimizing the risk of false-positive activation. Head motion can lead to severe image degradation and result in false-positive activation and is usually worse in patients than in healthy subjects. We performed general linear model fMRI data analysis on simultaneous EEG–fMRI data acquired in 34 cases with focal epilepsy. Signal changes associated with large inter-scan motion events (head jerks) were modelled using modified design matrices that include ‘scan nulling’ regressors. We evaluated the efficacy of this approach by mapping the proportion of the brain for which F-tests across the additional regressors were significant. In 95% of cases, there was a significant effect of motion in 50% of the brain or greater; for the scan nulling effect, the proportion was 36%; this effect was predominantly in the neocortex. We conclude that careful consideration of the motion-related effects in fMRI studies of patients with epilepsy is essential and that the proposed approach can be effective

Dynamic BOLD functional connectivity in humans and its electrophysiological correlates

Neural oscillations subserve many human perceptual and cognitive operations. Accordingly, brain functional connectivity is not static in time, but fluctuates dynamically following the synchronization and desynchronization of neural populations. This dynamic functional connectivity has recently been demonstrated in spontaneous fluctuations of the Blood Oxygen Level-Dependent (BOLD) signal, measured with functional Magnetic Resonance Imaging (fMRI). We analyzed temporal fluctuations in BOLD connectivity and their electrophysiological correlates, by means of long (≈50 min) joint electroencephalographic (EEG) and fMRI recordings obtained from two populations: 15 awake subjects and 13 subjects undergoing vigilance transitions. We identified positive and negative correlations between EEG spectral power (extracted from electrodes covering different scalp regions) and fMRI BOLD connectivity in a network of 90 cortical and subcortical regions (with millimeter spatial resolution). In particular, increased alpha (8-12 Hz) and beta (15-30 Hz) power were related to decreased functional connectivity, whereas gamma (30-60 Hz) power correlated positively with BOLD connectivity between specific brain regions. These patterns were altered for subjects undergoing vigilance changes, with slower oscillations being correlated with functional connectivity increases. Dynamic BOLD functional connectivity was reflected in the fluctuations of graph theoretical indices of network structure, with changes in frontal and central alpha power correlating with average path length. Our results strongly suggest that fluctuations of BOLD functional connectivity have a neurophysiological origin. Positive correlations with gamma can be interpreted as facilitating increased BOLD connectivity needed to integrate brain regions for cognitive performance. Negative correlations with alpha suggest a temporary functional weakening of local and long-range connectivity, associated with an idling state

An investigation of the relationship between BOLD and perfusion signal changes during epileptic generalised spike wave activity

In pathological conditions interpretation of functional magnetic resonance imaging (fMRI) results can be difficult. This is due to a reliance on the assumed coupling between neuronal activity and changes in cerebral blood flow (CBF) and oxygenation. We wanted to investigate the coupling between blood oxygen level dependant contrast (BOLD) and CBF time courses in epilepsy patients with generalised spike wave activity (GSW) to better understand the underlying mechanisms behind the EEG-fMRI signal changes observed, especially in regions of negative BOLD response (NBR). Four patients with frequent GSW were scanned with simultaneous electroencephalographic (EEG)-fMRI with BOLD and arterial spin labeling (ASL) sequences. We examined the relationship between simultaneous CBF and BOLD measurements by looking at the correlation of the two signals in terms of percentage signal change on a voxel-by-voxel basis. This method is not reliant on coincident activation. BOLD and CBF were positively correlated in patients with epilepsy during background EEG activity and GSW. The subject average value of the ΔCBF/ΔBOLD slope lay between +19 and +36 and also showed spatial variation which could indicate areas with altered vascular response. There was not a significant difference between ΔCBF/ΔBOLD during GSW, suggesting that neurovascular coupling to BOLD signal is generally maintained between states and, in particular, within areas of NBR

BOLD and perfusion changes during epileptic generalised spike wave activity

It is unclear whether neurovascular coupling is maintained during epileptic discharges. Knowing this is important to allow appropriate inferences from functional imaging studies of epileptic activity. Recent blood oxygen level-dependent (BOLD) functional MRI (fMRI) studies have demonstrated negative BOLD responses (NBR) in frontal, parietal and posterior cingulate cortices during generalised spike wave activity (GSW). We hypothesized that GSW-related NBR commonly reflect decreased cerebral blood flow (CBF). We measured BOLD and cerebral blood flow responses using simultaneous EEG with BOLD and arterial spin label (ASL) fMRI at 3 T. Four patients with epilepsy were studied; two with idiopathic generalized epilepsy (IGE) and two with secondary generalized epilepsy (SGE). We found GSW-related NBR in frontal, parietal and posterior cingulate cortices. We measured the coupling between BOLD and CBF changes during GSW and normal background EEG and found a positive correlation between the simultaneously measured BOLD and CBF throughout the imaged volume. Frontal and thalamic activation were seen in two patients with SGE, concordant with the electro-clinical features of their epilepsy. There was striking reproducibility of the GSW-associated BOLD response in subjects previously studied at 1.5 T. Our results show a preserved relationship between BOLD and CBF changes during rest and GSW activity consistent with normal neurovascular coupling in patients with generalized epilepsy and in particular during GSW activity. Cortical activations appear to reflect areas of discharge generation whilst deactivations reflect changes in conscious resting state activity

Potential for banks´ private mortgage financing business through the application of predictive analytics

Private mortgage financing accounts for a growing share of banks’ lending business and, thus, their profits. Yet increasing competition and tightening market conditions are pressuring profitability. This work project analyzes predictive analytics as a means to alleviate these challenges, focusing on the German market and relying on guided expert interviews for primary research. In particular, it outlines 17 existing and potential fields of application, and examines corresponding types of predictive analytics models and data sources. Furthermore, 12 major challenges associated with the implementation of predictive analytics are identified

Noncanonical spike-related BOLD responses in focal epilepsy

Till now, most studies of the Blood Oxygen Level-Dependent (BOLD) response to interictal epileptic discharges (IED) have assumed that its time course matches closely to that of brief physiological stimuli, commonly called the canonical event-related haemodynamic response function (canonical HRF). Analyses based on that assumption have produced significant response patterns that are generally concordant with prior electroclinical data. In this work, we used a more flexible model of the event-related response, a Fourier basis set, to investigate the presence of other responses in relation to individual IED in 30 experiments in patients with focal epilepsy. We found significant responses that had a noncanonical time course in 37% of cases, compared with 40% for the conventional, canonical HRF-based approach. In two cases, the Fourier analysis suggested activations where the conventional model did not. The noncanonical activations were almost always remote from the presumed generator of epileptiform activity. In the majority of cases with noncanonical responses, the noncanonical responses in single-voxel clusters were suggestive of artifacts. We did not find evidence for IED-related noncanonical HRFs arising from areas of pathology, suggesting that the BOLD response to IED is primarily canonical. Noncanonical responses may represent a number of phenomena, including artefacts and propagated epileptiform activity