Morphological parameters affecting false lumen thrombosis following type B aortic dissection: a systematic study based on simulations of idealized models.

Type B aortic dissection (TBAD) carries a high risk of complications, particularly with a partially thrombosed or patent false lumen (FL). Therefore, uncovering the risk factors leading to FL thrombosis is crucial to identify high-risk patients. Although studies have shown that morphological parameters of the dissected aorta are related to FL thrombosis, often conflicting results have been reported. We show that recent models of thrombus evolution in combination with sensitivity analysis methods can provide valuable insights into how combinations of morphological parameters affect the prospect of FL thrombosis. Based on clinical data, an idealized geometry of a TBAD is generated and parameterized. After implementing the thrombus model in computational fluid dynamics simulations, a global sensitivity analysis for selected morphological parameters is performed. We then introduce dimensionless morphological parameters to scale the results to individual patients. The sensitivity analysis demonstrates that the most sensitive parameters influencing FL thrombosis are the FL diameter and the size and location of intimal tears. A higher risk of partial thrombosis is observed when the FL diameter is larger than the true lumen diameter. Reducing the ratio of the distal to proximal tear size increases the risk of FL patency. In summary, these parameters play a dominant role in classifying morphologies into patent, partially thrombosed, and fully thrombosed FL. In this study, we point out the predictive role of morphological parameters for FL thrombosis in TBAD and show that the results are in good agreement with available clinical studies.

A Bayesian approach to blood rheological uncertainties in aortic hemodynamics.

Computational hemodynamics has received increasing attention recently. Patient-specific simulations require questionable model assumptions, for example, for geometry, boundary conditions, and material parameters. Consequently, the credibility of these simulations is much doubted, and rightly so. Yet, the matter may be addressed by a rigorous uncertainty quantification. In this contribution, we investigated the impact of blood rheological models on wall shear stress uncertainties in aortic hemodynamics obtained in numerical simulations. Based on shear-rheometric experiments, we compare the non-Newtonian Carreau model to a simple Newtonian model and a Reynolds number-equivalent Newtonian model. Bayesian Probability Theory treats uncertainties consistently and allows to include elusive assumptions such as the comparability of flow regimes. We overcome the prohibitively high computational cost for the simulation with a surrogate model, and account for the uncertainties of the surrogate model itself, too. We have two main findings: (1) The Newtonian models mostly underestimate the uncertainties as compared to the non-Newtonian model. (2) The wall shear stresses of specific persons cannot be distinguished due to largely overlapping uncertainty bands, implying that a more precise determination of person-specific blood rheological properties is necessary for person-specific simulations. While we refrain from a general recommendation for one rheological model, we have quantified the error of the uncertainty quantification associated with these modeling choices.

Monitoring of false lumen thrombosis in type B aortic dissection by impedance cardiography - A multiphysics simulation study.

Aortic dissection is caused by a tear on the aortic wall that allows blood to flow through the wall layers. Usually, this tear involves the intimal and partly the medial layer of the aortic wall. As a result, a new false lumen develops besides the original aorta, denoted then as the true lumen. The local hemodynamic conditions such as flow disturbances, recirculations and low wall shear stress may cause thrombus formation and growth in the false lumen. Since the false lumen status is a significant predictor for late-dissection-related deaths, it is of great importance in the medical management of patients with aortic dissection. The hemodynamic changes in the aorta also alter the electrical conductivity of blood. Since the blood is much more conductive than other tissues in the body, such changes can be identified with non-invasive methods such as impedance cardiography. Therefore, in this study, the capability of impedance cardiography in monitoring thrombosis in the false lumen is studied by multiphysics simulations to assist clinicians in the medical management of patients under treatment. To tackle this problem, a 3D computational fluid dynamics simulation has been set up to model thrombosis in the false lumen and its impact on the blood flow-induced conductivity changes. The electrical conductivity changes of blood have been assigned as material properties of the blood-filled aorta in a 3D finite element electric simulation model to investigate the impact of conductivity changes on the measured impedance from the body's surface. The results show remarkable changes in the electrical conductivity distribution in the measurement region due to thrombosis in the false lumen, which significantly impacts the morphology of the impedance cardiogram. Thus, frequent monitoring of impedance cardiography signals may allow tracking the thrombus formation and growth in the false lumen.

Educational Approach of Blended Learning in Teaching Benign Paroxysmal Positional Vertigo in an Emergency Department.

OBJECTIVE: To investigate the efficacy of blended learning (BL) in emergency medical resident education related to the diagnosis and treatment of benign paroxysmal positional vertigo. STUDY DESIGN: A mixed-method study. PLACE AND DURATION OF STUDY: Emergency Department of Hamad General Hospital, Doha, Qatar from 1st to 31st January 2018. METHODOLOGY: Participating emergency medical residents were assigned to either traditional lecturing (TL) or BL groups and they used several instruments to review medical knowledge and skills before and after instruction. The residents' opinions were sought through semi-structured interviews. RESULTS: Students in both groups possessed similar knowledge and skills improvement, but reported a strong preference for TL. CONCLUSION: There is a need for further evaluation of learning technology and students' learning styles to maximise medical education.

[Panic disorder and agoraphobia in general practice: Advantages and pitfalls of a practice team-supported exposure training from the general practitioner's perspective - a qualitative study]. / Panikstörung und Agoraphobie hausärztlich behandelt: Vorzüge und Fallstricke eines Praxisteam-unterstützten Expositionstrainings aus Sicht von Hausärztinnen und Hausärzten ­ eine qualitative Studie.

INTRODUCTION: For the treatment of anxiety disorders behavior therapy-oriented methods are recommended for primary care as well. Within the trial "Jena-PARADISE" a primary care practice team-supported exposure training for patients with panic disorder with or without agoraphobia was developed and evaluated. The present paper gives an overview of general practitioners' subjective views on the practicability, feasibility and effectiveness of this new intervention for both patients and GP teams. METHODS: Questions were operationalized based on Bellg's intervention fidelity framework. Fourteen GPs of the intervention group were sampled purposefully and interviewed in a semi-structured way. Generated data were analyzed following Mayring's content analysis approach. RESULTS: The treatment program was positively assessed among the GPs and seen as a useful therapeutic option for inadequately treated patients. The therapy elements 'psycho-education' and 'interoceptive exposure exercises' were described as feasible, while situational exercises and relapse prevention got a less positive rating. The active participation of the nurse in the treatment program was seen as supportive. CONCLUSION: From the GP perspective, the treatment program for patients with panic disorder and/or agoraphobia seems to be a viable therapeutic option in primary care.

[The Jena Anxiety Monitoring List (JAMoL) - a tool for the evidence-based treatment of panic disorder with or without agoraphobia in primary care]. / Die Jena Angst-Monitoring-Liste (JAMoL) - ein Instrument zur evidenzbasierten Behandlung von Panikstörung mit oder ohne Agoraphobie in der Hausarztpraxis.

BACKGROUND: Behavior therapy-oriented methods are recommended for treating anxiety disorders in primary care. The treatment of patients with long-term conditions can be improved by case management and structured clinical monitoring. The present paper describes the rationale, design and application of the 'Jena Anxiety Monitoring List' (JAMoL), a monitoring tool for the treatment of patients with panic disorder, with or without agoraphobia, in primary care. METHODS: JAMoL's design was based on established clinical measures, the rationale of exposure-based anxiety treatment, and research on family practice-based case management. After piloting, the JAMoL was used in the clinical study 'Jena-PARADISE' (ISRCTN64669297), where non-physician practice staff monitored patients with panic disorder by telephone. Using semi-structured interviews in concomitant studies, study participants were asked about the instrument's functionality. RESULTS: The JAMoL assesses the severity of anxiety symptoms (6 items) as well as the patient's adherence to therapy (4 items) and fosters the case management-related information exchange (3 items). An integrated traffic light scheme facilitates the evaluation of monitoring results. Within the clinical study, non-physician practice staff carried out a total of 1,525 JAMoL-supported monitoring calls on 177 patients from 30 primary care practices (median calls per patient: 10 [interquartile range, 9-10]). Qualitative analyses revealed that most practice teams and patients rated the JAMoL as a practicable and treatment-relevant tool. CONCLUSIONS: The JAMoL enables primary care practice teams to continuously monitor anxiety symptoms and treatment adherence in patients with panic disorder with or without agoraphobia. Within the behavior therapy-oriented treatment program 'Jena-PARADISE', the JAMoL constitutes an important case management tool.

A synthetic biology approach to transform Yarrowia lipolytica into a competitive biotechnological producer of ß-carotene.

The increasing market demands of ß-carotene as colorant, antioxidant and vitamin precursor, requires novel biotechnological production platforms. Yarrowia lipolytica, is an industrial organism unable to naturally synthesize carotenoids but with the ability to produce high amounts of the precursor Acetyl-CoA. We first found that a lipid overproducer strain was capable of producing more ß-carotene than a wild type after expressing the heterologous pathway. Thereafter, we developed a combinatorial synthetic biology approach base on Golden Gate DNA assembly to screen the optimum promoter-gene pairs for each transcriptional unit expressed. The best strain reached a production titer of 1.5 g/L and a maximum yield of 0.048 g/g of glucose in flask. ß-carotene production was further increased in controlled conditions using a fed-batch fermentation. A total production of ß-carotene of 6.5 g/L and 90 mg/g DCW with a concomitant production of 42.6 g/L of lipids was achieved. Such high titers suggest that engineered Y. lipolytica is a competitive producer organism of ß-carotene.

Contrast adaptation: paradoxical effects when the temporal frequencies of adaptation and test differ.

Previous studies of human contrast adaptation employing visually evoked potentials (VEP) have revealed contradictory results, namely, either a reduction or an enhancement in VEP amplitude. In a cross-adaptation experiment, we explored the possibility that differences in the temporal frequency of adapting and test patterns played a role. Phase-reversing checkerboard stimuli [1-deg check size, temporal frequency 8.5 or 17 reversals per second (rps)] served as adaptation and test pattern with contrasts of 0 or 97%. In 13 subjects, we recorded both retinal (PERG) and cortical (VEP) steady-state responses simultaneously. In a balanced block design, all four combinations of the temporal adaptation and test frequencies were employed. Contrast adaptation reduced the PERG amplitude by about 20% in every temporal condition (P < 0.001). The VEP amplitude was strongly affected by adaptation, but the effect differed in magnitude and sign depending on condition: With identical adaptation and test frequency, amplitude was reduced by 15% (P = 0.07) at 8.5 rps and by 38% at 17 rps (P < 0.05). Adapting at 8.5 rps and testing at 17 rps had a tiny (14%) insignificant effect, whereas adapting at 17 rps and testing at 8.5 rps revealed an amplitude enhancement of 27% (P < 0.05). These strong temporal cross-adaptation effects (in the VEP, but not in the PERG) suggest that the adaptable cortical mechanisms (gain control) can be narrowly tuned in their temporal properties. A sizable adaptation effect can even change its sign when varying the temporal frequency by a factor of two. This finding resolves contradictions between previous VEP adaptation studies and reconciles them with psychophysical findings.

Contrast adaptation in retinal and cortical evoked potentials: no adaptation to low spatial frequencies.

Contrast adaptation occurs in both the retina and the cortex. Defining its spatial dependence is crucial for understanding its potential roles. We thus asked to what degree contrast adaptation depends on spatial frequency, including cross-adaptation. Measuring the pattern electroretinogram (PERG) and the visual evoked potential (VEP) allowed separating retinal and cortical contributions. In ten subjects we recorded simultaneous PERGs and VEPs. Test stimuli were sinusoidal gratings of 98% contrast with spatial frequencies of 0.5 or 5.0 cpd, phase reversing at 17 reversals/s. Adaptation was controlled by prolonged presentation of these test stimuli or homogenous gray fields of the same luminance. When adaptation and test frequency were identical, we observed significant contrast adaptation only at 5 cpd: an amplitude reduction in the PERG (-22%) and VEP (-58%), and an effective reduction of latency in the PERG (-0.95 ms). When adapting at 5 cpd and testing at 0.5 cpd, the opposite effect was observed: enhancement of VEP amplitude by +26% and increase in effective PERG latency by + 1.35 ms. When adapting at 0.5 cpd and testing at 5 cpd, there was no significant amplitude change in PERG and VEP, but a small effective PERG latency increase of +0.65 ms. The 0.5-cpd channel was not adapted by spatial frequencies of 0.5 cpd. The adaptability of the 5-cpd channel may mediate improved detail recognition after prolonged blur. The existence of both adaptable and nonadaptable mechanisms in the retina allows for the possibility that by comparing the adaptational state of spatial-frequency channels the retina can discern between overall low contrast and defocus in emmetropization control.