Outcomes of three different ways to train medical students as ultrasound tutors.

BACKGROUND: In order to provide faculty-wide undergraduate ultrasound training in times of scarce resources, many medical faculties employ trained peer-student tutors to oversee the hands-on training. However, data to guide the training of ultrasound peer-student tutors are scarce. We conducted a prospective quasi-randomized study to assess the gain in theoretical knowledge and practical scanning skills of peer-student tutors who were trained with a course only, an internship only, or the combination of a course and an internship. METHODS: A total of 44 peer-student tutors were trained by a one-week course only (C-Group, n = 21), by an internship only (I-Group, n = 10) or by a course and an internship (CI-Group, n = 13). Prior to and after the completion of the training the peer-student tutors completed an MC-test (theoretical knowledge) and an OSCE (practical scanning skills). RESULTS: With all three education concepts, the peer-student tutors had significant and comparable gains in theoretical knowledge (C-group + 90%, I-group + 61.5%, CI-group + 114.0%) and practical scanning skills (C-group + 112.0%, I-group + 155.0% and CI-group + 123.5%), all p < 0.001. CONCLUSION: Peer-student tutors, who were trained with a course or an internship or a course and internship improved their theoretical knowledge and their practical scanning skills significantly and to a comparable degree.

TRAF5 deficiency accelerates atherogenesis in mice by increasing inflammatory cell recruitment and foam cell formation.

RATIONALE: Tumor necrosis factor receptor-associated factors (TRAFs) are cytoplasmic adaptor proteins for the TNF/interleukin-1/Toll-like receptor superfamily. Ligands of this family comprise multiple important cytokines such as TNFα, CD40L, and interleukin-1ß that promote chronic inflammatory diseases such as atherosclerosis. We recently reported overexpression of TRAF5 in murine and human atheromata and that TRAF5 promotes inflammatory functions of cultured endothelial cells and macrophages. OBJECTIVE: This study tested the hypothesis that TRAF5 modulates atherogenesis in vivo. METHODS AND RESULTS: Surprisingly, TRAF5(-/-)/LDLR(-/-) mice consuming a high-cholesterol diet for 18 weeks developed significantly larger atherosclerotic lesions than did TRAF5(+/+)/LDLR(-/-) controls. Plaques of TRAF5-deficient animals contained more lipids and macrophages, whereas smooth muscle cells and collagen remained unchanged. Deficiency of TRAF5 in endothelial cells or in leukocytes enhanced adhesion of inflammatory cells to the endothelium in dynamic adhesion assays in vitro and in murine vessels imaged by intravital microscopy in vivo. TRAF5 deficiency also increased expression of adhesion molecules and chemokines and potentiated macrophage lipid uptake and foam cell formation. These findings coincided with increased activation of JNK and appeared to be independent of TRAF2. Finally, patients with stable or acute coronary heart disease had significantly lower amounts of TRAF5 mRNA in blood compared with healthy controls. CONCLUSIONS: Unexpectedly, TRAF5 deficiency accelerates atherogenesis in mice, an effect likely mediated by increased inflammatory cell recruitment to the vessel wall and enhanced foam cell formation.

Tumor necrosis factor receptor-associated factor 1 (TRAF1) deficiency attenuates atherosclerosis in mice by impairing monocyte recruitment to the vessel wall.

BACKGROUND: Members of the tumor necrosis factor superfamily, such as tumor necrosis factor-alpha, potently promote atherogenesis in mice and humans. Tumor necrosis factor receptor-associated factors (TRAFs) are cytoplasmic adaptor proteins for this group of cytokines. METHODS AND RESULTS: This study tested the hypothesis that TRAF1 modulates atherogenesis in vivo. TRAF1(-/-)/LDLR(-/-) mice that consumed a high-cholesterol diet for 18 weeks developed significantly smaller atherosclerotic lesions than LDLR(-/-) (LDL receptor-deficient) control animals. As the most prominent change in histological composition, plaques of TRAF1-deficient animals contained significantly fewer macrophages. Bone marrow transplantations revealed that TRAF1 deficiency in both hematopoietic and vascular resident cells contributed to the reduction in atherogenesis observed. Mechanistic studies showed that deficiency of TRAF1 in endothelial cells and monocytes reduced adhesion of inflammatory cells to the endothelium in static and dynamic assays. Impaired adhesion coincided with reduced cell spreading, actin polymerization, and CD29 expression in macrophages, as well as decreased expression of the adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in endothelial cells. Small interfering RNA studies in human cells verified these findings. Furthermore, TRAF1 messenger RNA levels were significantly elevated in the blood of patients with acute coronary syndrome. CONCLUSIONS: TRAF1 deficiency attenuates atherogenesis in mice, most likely owing to impaired monocyte recruitment to the vessel wall. These data identify TRAF1 as a potential treatment target for atherosclerosis.

Online EEG-Based Workload Adaptation of an Arithmetic Learning Environment.

In this paper, we demonstrate a closed-loop EEG-based learning environment, that adapts instructional learning material online, to improve learning success in students during arithmetic learning. The amount of cognitive workload during learning is crucial for successful learning and should be held in the optimal range for each learner. Based on EEG data from 10 subjects, we created a prediction model that estimates the learner's workload to obtain an unobtrusive workload measure. Furthermore, we developed an interactive learning environment that uses the prediction model to estimate the learner's workload online based on the EEG data and adapt the difficulty of the learning material to keep the learner's workload in an optimal range. The EEG-based learning environment was used by 13 subjects to learn arithmetic addition in the octal number system, leading to a significant learning effect. The results suggest that it is feasible to use EEG as an unobtrusive measure of cognitive workload to adapt the learning content. Further it demonstrates that a promptly workload prediction is possible using a generalized prediction model without the need for a user-specific calibration.

Asynchronous P300 classification in a reactive brain-computer interface during an outlier detection task.

OBJECTIVE: In this study, the feasibility of detecting a P300 via an asynchronous classification mode in a reactive EEG-based brain-computer interface (BCI) was evaluated. The P300 is one of the most popular BCI control signals and therefore used in many applications, mostly for active communication purposes (e.g. P300 speller). As the majority of all systems work with a stimulus-locked mode of classification (synchronous), the field of applications is limited. A new approach needs to be applied in a setting in which a stimulus-locked classification cannot be used due to the fact that the presented stimuli cannot be controlled or predicted by the system. APPROACH: A continuous observation task requiring the detection of outliers was implemented to test such an approach. The study was divided into an offline and an online part. MAIN RESULTS: Both parts of the study revealed that an asynchronous detection of the P300 can successfully be used to detect single events with high specificity. It also revealed that no significant difference in performance was found between the synchronous and the asynchronous approach. SIGNIFICANCE: The results encourage the use of an asynchronous classification approach in suitable applications without a potential loss in performance.

Cognitive state monitoring and the design of adaptive instruction in digital environments: lessons learned from cognitive workload assessment using a passive brain-computer interface approach.

According to Cognitive Load Theory (CLT), one of the crucial factors for successful learning is the type and amount of working-memory load (WML) learners experience while studying instructional materials. Optimal learning conditions are characterized by providing challenges for learners without inducing cognitive over- or underload. Thus, presenting instruction in a way that WML is constantly held within an optimal range with regard to learners' working-memory capacity might be a good method to provide these optimal conditions. The current paper elaborates how digital learning environments, which achieve this goal can be developed by combining approaches from Cognitive Psychology, Neuroscience, and Computer Science. One of the biggest obstacles that needs to be overcome is the lack of an unobtrusive method of continuously assessing learners' WML in real-time. We propose to solve this problem by applying passive Brain-Computer Interface (BCI) approaches to realistic learning scenarios in digital environments. In this paper we discuss the methodological and theoretical prospects and pitfalls of this approach based on results from the literature and from our own research. We present a strategy on how several inherent challenges of applying BCIs to WML and learning can be met by refining the psychological constructs behind WML, by exploring their neural signatures, by using these insights for sophisticated task designs, and by optimizing algorithms for analyzing electroencephalography (EEG) data. Based on this strategy we applied machine-learning algorithms for cross-task classifications of different levels of WML to tasks that involve studying realistic instructional materials. We obtained very promising results that yield several recommendations for future work.

Tumor necrosis factor receptor associated factor 6 is not required for atherogenesis in mice and does not associate with atherosclerosis in humans.

BACKGROUND: Tumor necrosis factor receptor-associated factors (TRAFs) are important signaling molecules for a variety of pro-atherogenic cytokines including CD40L, TNF alpha, and IL1beta. Several lines of evidence identified TRAF6 as a pro-inflammatory signaling molecule in vitro and we previously demonstrated overexpression of TRAF6 in human and Murine atherosclerotic plaques. This study investigated the role of TRAF6-deficiency in mice developing atherosclerosis, a chronic inflammatory disease. METHODOLOGY/PRINCIPAL FINDINGS: Lethally irradiated low density lipoprotein receptor-deficient mice (TRAF6(+/+)/LDLR(-/-)) were reconstituted with TRAF6-deficient fetal liver cells (FLC) and consumed high cholesterol diet for 18 weeks to assess the relevance of TRAF6 in hematopoietic cells for atherogenesis. Additionally, TRAF6(+/-)/LDLR(-/-) mice received TRAF6-deficient FLC to gain insight into the role of TRAF6 deficiency in resident cells. Surprisingly, atherosclerotic lesion size did not differ between the three groups in both aortic roots and abdominal aortas. Similarly, no significant differences in plaque composition could be observed as assessed by immunohistochemistry for macrophages, lipids, smooth muscle cells, T-cells, and collagen. In accord, in a small clinical study TRAF6/GAPDH total blood RNA ratios did not differ between groups of patients with stable coronary heart disease (0.034+/-0.0021, N = 178), acute coronary heart disease (0.029+/-0.0027, N = 70), and those without coronary heart disease (0.032+/-0.0016, N = 77) as assessed by angiography. CONCLUSION: Our study demonstrates that TRAF6 is not required for atherogenesis in mice and does not associate with clinical disease in humans. These data suggest that pro- and anti-inflammatory features of TRAF6 signaling outweigh each other in the context of atherosclerosis.

CD40L induces inflammation and adipogenesis in adipose cells--a potential link between metabolic and cardiovascular disease.

CD40L figures prominently in atherogenesis. Recent data demonstrate elevated levels of sCD40L in the serum of patients with the metabolic syndrome (MS). This study investigated the role of CD40L in pro-inflammatory gene expression and cellular differentiation in adipose tissue to obtain insight into mechanisms linking the MS with atherosclerosis. Human adipocytes and preadipocytes expressed CD40 but not CD40L. Stimulation with recombinant CD40L or membranes over-expressing CD40L induced a time- and dose-dependent expression of IL-6, MCP-1, IL-8, and PAI-1. Supernatants of CD40L-stimulated adipose cells activated endothelial cells, suggesting a systemic functional relevance of our findings. Neutralising antibodies against CD40L attenuated these effects substantially. Signalling studies revealed the involvement of mitogen-activated protein kinases and NFkB. Furthermore, stimulation with CD40L resulted in enhanced activation of C/EBPa and PPARg and promoted adipogenesis of preadipose cells in the presence and absence of standard adipogenic conditions. Finally, patients suffering from the metabolic syndrome with high levels of sCD40L also displayed high levels of IL-6, in line with the concept that CD40L may induce the expression of inflammatory cytokines in vivo in this population. Our data reveal potent metabolic functions of CD40L aside from its known pivotal pro-inflammatory role within plaques. Our data suggest that CD40L may mediate risk at the interface of metabolic and atherothrombotic disease.