Bi-ventricular axial micropump: impact on blood cell integrity.

BACKGROUND AND OBJECTIVE: Off-pump coronary artery bypass grafting has stimulated the development of micro-pumps designed to prevent the hemodynamic instability induced by heart luxation for the exposure of target vessels of the posterior wall. Impella (Aachen, Germany) developed micro-pumps with a miniaturized propeller system for both sides of the heart. The aim of this study was to analyze the impact of both pumps working together on blood cell integrity. MATERIALS AND METHODS: Both right and left-sided micro-pumps were implanted in 5 calves (body weight, 72_4 Kg) during 3 h. Blood samples for hematology and hemolysis parameters were drawn hourly. RESULTS: Both pumps performed well with a flow of 3.6 L +/- 0.3 L during the 3 h of the experiment with stable hemodynamic conditions. Mixed venous oxygen saturation was 63.4 +/- 15.2% at baseline and 63.8 +/- 16.3% at the end of the experiment (P = ns). Red cell count, LDH and free plasma hemoglobin were 6.7 +/- 2.1 x 10(12)/L, 1807 +/- 437 IU/L, and 32 +/- 9 mg/L at baseline vs. 6.1 +/- 2.1 x 10(12)/L, 1871 +/- 410 IU/L, and 52 +/- 9 mg/L at the end of the experiment (P = ns for all comparisons). Platelet count exhibited a non-significant drop (872 +/- 126 vs. 715 +/- 22 x 10(9)/L). CONCLUSIONS: This double pump system based on the Archimed screw principle is hematologically well tolerated under conditions of prolonged cardiac assist.

Spatial learning by rats across visually disconnected environments

Experiments were designed to examine some properties of spatial representations in rats. Adult subjects were trained to escape through a hole at a fixed position in a large circular arena (see Schenk 1989). The experiments were conducted in the dark, with a limited number of controlled visual light cues in order to assess the minimal cue requirement for place learning. Three identical light cues (shape, height and distance from the table) were used. Depending on the condition, they were either permanently on, or alternatively on or off, depending on the position of the rat in the field. Two questions were asked: a) how many identical visual cues were necessary for spatial discrimination in the dark, and b) could rats integrate the relative positions of separate cues, under conditions in which the rat was never allowed to perceive all three cues simultaneously. The results suggest that rats are able to achieve a place discrimination task even if the three cues necessary for efficient orientation can never be seen simultaneously. A dissociation between the discrimination of the spatial position of the goal and the capacity to reach it by a direct path suggests that a reduced number of cues might require prolonged locomotion to allow an accurate orientation in the environment.

Indirect effects of peri-and postnatal choline treatment on place-learning abilities in rat.

This work was aimed at analyzing the effects of perinatal choline supplementation on the development of spatial abilities and upon adult performance. Choline supplementation (3.5 g/L in 0.02 M saccharin solution in tap water) was maintained for two weeks before birth and for up to four weeks postnatally. Additional supplementation was maintained from the fifth to the tenth week postnatally. Spatial-learning capacities were studied at the ages of 26, 65, or 80 days in a circular swimming pool (Morris place-navigation task) and at the age of 7 months in a homing arena. Treatment effects were found in both juvenile and adult rats, and thus persisted for several months after the cessation of the supplementation. The choline supplementation improved the performance in the water maze in a very selective manner. The most consistent effect was a reduction in the latency to reach a cued platform at a fixed position in space, whereas the improvement was limited when the platform was invisible and had to be located relative to distant cues only. However, after removal of the goal cue, the treated rats showed a better retention of the training position than did the control rats. A similar effect was observed in a dry-land task conducted in the homing arena. The choline supplementation thus induced a significant improvement of spatial memory. But since this effect was only evident following training with a salient cue, it might be regarded as an indirect effect promoted by an optimal combination of cue guidance with a place strategy.

MENTAL IMAGERY IN PERCEPTUAL LEARNING

L'imagerie mentale est définie comme une expérience similaire à la perception mais se déroulant en l'absence d'une stimulation physique. Des recherches antérieures ont montré que l'imagerie mentale améliore la performance dans certains domaines, comme par exemple le domaine moteur. Cependant, son rôle dans l'apprentissage perceptif n'a pas encore été étudié. L'apprentissage perceptif correspond à l'amélioration permanente des performances suite à la répétition de la même tâche. Cette thèse présente une série des résultats empiriques qui montrent que l'apprentissage perceptif peut aussi être achevé en l'absence des stimuli physiques. En effet, imaginer des stimuli visuels amène à une meilleure performance avec les stimuli réels. Donc, les processus sous-jacents l'apprentissage perceptif ne sont pas uniquement déclenchés par les stimuli sensoriels, mais également par des signaux internes. En plus, l'apprentissage perceptif à travers l'imagerie mentale ne se réalise que seule-ment quand les stimuli ne sont pas (complètement) présents, mais gaiement quand les stimuli montrés ne sont pas utiles quant à la résolution de la tâche. - Mental imagery is described as an experience that resembles pereeptnal ex-perience but which occurs in the absence ef a physical stimulation. Despite its beneficial effects in, among others, motor performance, the role of mental imagery m perceptual learning has not yet been addressed. Here we focus on a specific sensory modality: vision. Perceptual learning is the ability to improve perception in a stable way through the repetition of a given task Here I demonstrate by a series of empirical results that a perceptual improve¬ment can also occur in the absence of a stimulation. Imagining visual stimuli is sufficient for successful perceptual learning. Hence, processes underlying perceptual learning are not only stimulus-driven but can also be driven by internally generated signals. Moreover, I also show that perceptual learning via mental imagery can occur not only when physical stimuli are (partially) absent, but also in conditions where stimuli are uninformative with respect to the task that has to be learned.

LDLs stimulate p38 MAPKs and wound healing through SR-BI independently of Ras and PI3 kinase.

Intracellular signals elicited by LDLs are likely to play a role in the pathogenesis associated with increased LDL blood levels. We have previously determined that LDL stimulation of human skin fibroblasts, used as a model system for adventitial fibroblasts, activates p38 mitogen-activated protein kinases (MAPKs), followed by IL-8 production and increased wound-healing capacity of the cells. The proximal events triggering these responses had not been characterized, however. Here we show that MAPK kinases MKK3 and MKK6, but not MKK4, are the upstream kinases responsible for the activation of the p38 MAPKs and stimulation of wound closure in response to LDLs. Phosphoinositide 3 kinases (PI3Ks) and Ras have been suggested to participate in lipoprotein-induced MAPK activation. However, specific PI3K inhibitors or expression of a dominant-negative form of Ras failed to blunt LDL-induced p38 MAPK activation. The classical LDL receptor does not participate in LDL signaling, but the contribution of other candidate lipoprotein receptors has not been investigated. Using cells derived from scavenger receptor class B type I (SR-BI) knockout mice or the BLT-1 SR-BI inhibitor, we now show that this receptor is required for LDLs to stimulate p38 MAPKs and to promote wound healing. Identification of MKK3/6 and SR-BI as cellular relays in LDL-mediated p38 activation further defines the signaling events that could participate in LDL-mediated pathophysiological responses.

Reduced learning ability as a consequence of evolutionary adaptation to nutritional stress in Drosophila melanogaster

1. Dietary conditions affect cognitive abilities of many species, but it is unclear to what extent this physiological effect translates into an evolutionary relationship. 2. A reduction of competitive ability under nutritional stress has been reported as a correlated response to selection for learning ability in Drosophila melanogaster. Here we test whether the reverse holds as well, i.e. whether an evolutionary adaptation to poor food conditions leads to a decrease in learning capacities. 3. Populations of D. melanogaster were: (i) not subject to selection (control), (ii) selected for improved learning ability, (iii) selected for survival and fast development on poor food, or (iv) subject to both selection regimes. 4. There was no detectable response to selection for learning ability. 5. Selection on poor food led to higher survival, faster development and smaller adult size as a direct response, and to reduced learning ability as a correlated response. This study supports the hypothesis that adaptation to poor nutrition is likely to trade off with the evolution of improved learning ability.

On optimal learning schedules and the marginal value of cumulative cultural evolution.

The age-dependent choice between expressing individual learning (IL) or social learning (SL) affects cumulative cultural evolution. A learning schedule in which SL precedes IL is supportive of cumulative culture because the amount of nongenetically encoded adaptive information acquired by previous generations can be absorbed by an individual and augmented. Devoting time and energy to learning, however, reduces the resources available for other life-history components. Learning schedules and life history thus coevolve. Here, we analyze a model where individuals may have up to three distinct life stages: "infants" using IL or oblique SL, "juveniles" implementing IL or horizontal SL, and adults obtaining material resources with learned information. We study the dynamic allocation of IL and SL within life stages and how this coevolves with the length of the learning stages. Although no learning may be evolutionary stable, we find conditions where cumulative cultural evolution can be selected for. In that case, the evolutionary stable learning schedule causes individuals to use oblique SL during infancy and a mixture between IL and horizontal SL when juvenile. We also find that the selected pattern of oblique SL increases the amount of information in the population, but horizontal SL does not do so.

Train-the-trainer: E-learning zur Förderung einer praxisorientiertem Vermittlung von evidenzbasierter Medizin

Hintergrund: Trotz ihrer Etablierung als essentieller Bestandteil der medizinischen Weiter-/Fortbildung werden europa- wie schweizweit kaum Kurse in evidenzbasierter Medizin (ebm) angeboten, die - integriert im klinischen Alltag - gezielt Fertigkeiten in ebm vermitteln. Noch grössere Defizite finden sich bei ebm- Weiterbildungsmöglichkeiten für klinische Ausbilder (z.B. Oberärzte). Als Weiterführung eines EU-finanzierten, klinisch integrierten E-learning- Programms für Weiterbildungsassistenten (www.ebm-unity.org) entwickelte eine europäische Gruppe von medical educators gezielt für Ausbilder ein e-learning-Curriculum zur Vermittlung von ebm im Rahmen der klinischen Weiterbildung. Methode: Die Entwicklung des Curriculums umfasst folgende Schritte: Beschreibung von Lernzielen, Identifikation von klinisch relevanten Lernumgebungen, Entwicklung von Lerninhalten und exemplarischen didaktischen Strategien, zugeschnitten auf die jeweilige Lernumgebungen, Design von web-basierten Selbst-Lernsequenzen mit Möglichkeiten zur Selbstevaluation, Erstellung eines Handbuchs. Ergebnisse: Lernziele des Tutoren-Lehrgangs sind der Erwerb von Fertigkeiten zur Vermittlung der 5 klassischen ebm-Schritte: PICO- (Patient-Intervention-Comparison-Outcome)-Fragen, Literatursuche, kritische Literaturbewertung, Übertragung der Ergebnisse im eigenen Setting und Implementierung). Die Lehrbeispiele zeigen angehenden ebm-Tutoren, wie sich typische klinische Situationen wie z.B. Stationsvisite, Ambulanzsprechstunde, Journalclub, offizielle Konferenzen, Audit oder das klinische Assessment von Weiterbildungsassistenten gezielt für die Vermittlung von ebm nutzen lassen. Kurze E-Learning-Module mit exemplarischen «real-life»-Video-Clips erlauben flexibles Lernen zugeschnitten auf das knappe Zeitkontingent von Ärzten. Eine Selbst-Evaluation ermöglicht die Überprüfung der gelernten Inhalte. Die Pilotierung des Tutoren-Lehrgangs mit klinisch tätigen Tutoren sowie die Übersetzung des Moduls in weitere Sprachen sind derzeit in Vorbereitung. chlussfolgerung: Der modulare Train-the-Trainer-Kurs zur Vermittlung von ebm im klinischen Alltag schliesst eine wichtige Lücke in der Dissemination von klinischer ebm. Webbasierte Beispiele mit kurzen Sequenzen demonstrieren typische Situationen zur Vermittlung der ebm-Kernfertigkeiten und bieten medical educators wie Oberärzten einen niedrigschwelligen Einstieg in «ebm» am Krankenbett. Langfristiges Ziel ist eine europäische Qualifikation für ebm- Learning und -Teaching in der Fort- und Weiterbildung. Nach Abschluss der Evaluation steht das Curriculum interessierten Personen und Gruppen unter «not-for-profit»-Bedingungen zur Verfügung. Auskünfte erhältlich von rkunz@uhbs.ch. Finanziert durch die Europäische Kommission - Leonardo da Vinci Programme - Transfer of Innovation - Pilot Project for Lifelong Learn- ing 2007 und das Schweizerische Staatssekretariat für Bildung und Forschung.

Implementing statistical learning methods through Bayesian networks (Part 2): bayesian evaluations for results of black toner analyses in forensic document examination

This paper presents and discusses the use of Bayesian procedures - introduced through the use of Bayesian networks in Part I of this series of papers - for 'learning' probabilities from data. The discussion will relate to a set of real data on characteristics of black toners commonly used in printing and copying devices. Particular attention is drawn to the incorporation of the proposed procedures as an integral part in probabilistic inference schemes (notably in the form of Bayesian networks) that are intended to address uncertainties related to particular propositions of interest (e.g., whether or not a sample originates from a particular source). The conceptual tenets of the proposed methodologies are presented along with aspects of their practical implementation using currently available Bayesian network software.

Morphologic and electroretinographic phenotype of SR-BI knockout mice after a long-term atherogenic diet.

PURPOSE: To evaluate functional and ultrastructural changes in the retina of scavenger receptor B1 (SR-BI) knockout (KO) mice consuming a high fat cholate (HFC) diet. METHODS: Three-month-old male KO and wild-type (WT) mice were fed an HFC diet for 30 weeks. After diet supplementation, plasma cholesterol levels and electroretinograms were analyzed. Neutral lipids were detected with oil red O, and immunohistochemistry was performed on cryostat ocular tissue sections. The retina, Bruch's membrane (BM), retinal pigment epithelium (RPE), and choriocapillaris (CC) were analyzed by transmission electron microscopy. RESULTS: Using the WT for reference, ultrastructural changes were recorded in HFC-fed SR-BI KO mice, including lipid inclusions, a patchy disorganization of the photoreceptor outer segment (POS) and the outer nuclear layer (ONL), and BM thickening with sparse sub-RPE deposits. Within the CC, there was abnormal disorganization of collagen fibers localized in ectopic sites with sparse and large vacuolization associated with infiltration of macrophages in the subretinal space, reflecting local inflammation. These lesions were associated with electroretinographic abnormalities, particularly increasing implicit time in a- and b-wave scotopic responses. Abnormal vascular endothelial growth factor (VEGF) staining was detected in the outer nuclear layer. CONCLUSIONS: HFC-fed SR-BI KO mice thus presented sub-RPE lipid-rich deposits and functional and morphologic alterations similar to some features observed in dry AMD. The findings lend further support to the hypothesis that atherosclerosis causes retinal and subretinal damage that increases susceptibility to some forms of AMD.

Learning spatial filters for multispectral image segmentation

We present a novel filtering method for multispectral satellite image classification. The proposed method learns a set of spatial filters that maximize class separability of binary support vector machine (SVM) through a gradient descent approach. Regularization issues are discussed in detail and a Frobenius-norm regularization is proposed to efficiently exclude uninformative filters coefficients. Experiments carried out on multiclass one-against-all classification and target detection show the capabilities of the learned spatial filters.

Kernel-based methods for change detection in remote sensing images

Nowadays, the joint exploitation of images acquired daily by remote sensing instruments and of images available from archives allows a detailed monitoring of the transitions occurring at the surface of the Earth. These modifications of the land cover generate spectral discrepancies that can be detected via the analysis of remote sensing images. Independently from the origin of the images and of type of surface change, a correct processing of such data implies the adoption of flexible, robust and possibly nonlinear method, to correctly account for the complex statistical relationships characterizing the pixels of the images. This Thesis deals with the development and the application of advanced statistical methods for multi-temporal optical remote sensing image processing tasks. Three different families of machine learning models have been explored and fundamental solutions for change detection problems are provided. In the first part, change detection with user supervision has been considered. In a first application, a nonlinear classifier has been applied with the intent of precisely delineating flooded regions from a pair of images. In a second case study, the spatial context of each pixel has been injected into another nonlinear classifier to obtain a precise mapping of new urban structures. In both cases, the user provides the classifier with examples of what he believes has changed or not. In the second part, a completely automatic and unsupervised method for precise binary detection of changes has been proposed. The technique allows a very accurate mapping without any user intervention, resulting particularly useful when readiness and reaction times of the system are a crucial constraint. In the third, the problem of statistical distributions shifting between acquisitions is studied. Two approaches to transform the couple of bi-temporal images and reduce their differences unrelated to changes in land cover are studied. The methods align the distributions of the images, so that the pixel-wise comparison could be carried out with higher accuracy. Furthermore, the second method can deal with images from different sensors, no matter the dimensionality of the data nor the spectral information content. This opens the doors to possible solutions for a crucial problem in the field: detecting changes when the images have been acquired by two different sensors.