In vivo myocardial tissue characterization of all four chambers using high-resolution quantitative MRI

Quantitative native T(1) Mapping of the myocardium without the application of contrast agents can be used to detect fibrosis in the left ventricle. Spatial resolution of standard native T(1) mapping is limited by cardiac motion and hence is not sufficient to resolve small myocardial structures, such as the right ventricle and the atria. Here, we present a novel MR approach which provides cardiac motion information and native T(1) maps from the same data. Motion information is utilized to optimize data selection for T(1) mapping and a model-based iterative reconstruction scheme ensures high-resolution T(1) maps for the entire heart. Feasibility of the approach was demonstrated in three healthy volunteers. In the T(1) maps, the myocardium of all four chambers can be visualized and T(1) values of the left atrium and right chambers were comparable to left ventricular T(1) values

(Quantum) Space-Time as a Statistical Geometry of Fuzzy Lumps and the Connection with Random Metric Spaces

We develop a kind of pregeometry consisting of a web of overlapping fuzzy lumps which interact with each other. The individual lumps are understood as certain closely entangled subgraphs (cliques) in a dynamically evolving network which, in a certain approximation, can be visualized as a time-dependent random graph. This strand of ideas is merged with another one, deriving from ideas, developed some time ago by Menger et al, that is, the concept of probabilistic- or random metric spaces, representing a natural extension of the metrical continuum into a more microscopic regime. It is our general goal to find a better adapted geometric environment for the description of microphysics. In this sense one may it also view as a dynamical randomisation of the causal-set framework developed by e.g. Sorkin et al. In doing this we incorporate, as a perhaps new aspect, various concepts from fuzzy set theory.Comment: 25 pages, Latex, no figures, some references added, some minor changes added relating to previous wor

Strong Field Control of the Interatomic Coulombic Decay Process in Quantum Dots

In recent years the laser induced interatomic Coulombic decay ICD process in paired quantum dots has been predicted [J. Chem. Phys. 138 2013 214104]. In this work we target the enhancement of ICD by scanning over a range of strong field laser intensities. The GaAs quantum dots are modeled by a one dimensional double well potential in which simulations are done with the space resolved multi configuration time dependent Hartree method including antisymmetrization to account for the fermions. As a novelty a complementary state resolved ansatz is developed to consolidate the interpretation of transient state populations, widths obtained for the ICD and the competing direct ionization channel, and Fano peak profiles in the photoelectron spectra. The major results are that multi photon processes are unimportant even for the strongest fields. Further, below pi to pi pulses display the highest ICD efficiency while the direct ionization becomes less dominan

High spatial resolution and temporally resolved t(2) (*) mapping of normal human myocardium at 7.0 tesla: an ultrahigh field magnetic resonance feasibility study

Myocardial tissue characterization using T(2) (*) relaxation mapping techniques is an emerging application of (pre)clinical cardiovascular magnetic resonance imaging. The increase in microscopic susceptibility at higher magnetic field strengths renders myocardial T(2) (*) mapping at ultrahigh magnetic fields conceptually appealing. This work demonstrates the feasibility of myocardial T(2) (*) imaging at 7.0 T and examines the applicability of temporally-resolved and high spatial resolution myocardial T(2) (*) mapping. In phantom experiments single cardiac phase and dynamic (CINE) gradient echo imaging techniques provided similar T(2) (*) maps. In vivo studies showed that the peak-to-peak B(0) difference following volume selective shimming was reduced to approximately 80 Hz for the four chamber view and mid-ventricular short axis view of the heart and to 65 Hz for the left ventricle. No severe susceptibility artifacts were detected in the septum and in the lateral wall for T(2) (*) weighting ranging from TE = 2.04 ms to TE = 10.2 ms. For TE >7 ms, a susceptibility weighting induced signal void was observed within the anterior and inferior myocardial segments. The longest T(2) (*) values were found for anterior (T(2) (*) = 14.0 ms), anteroseptal (T(2) (*) = 17.2 ms) and inferoseptal (T(2) (*) = 16.5 ms) myocardial segments. Shorter T(2) (*) values were observed for inferior (T(2) (*) = 10.6 ms) and inferolateral (T(2) (*) = 11.4 ms) segments. A significant difference (p = 0.002) in T(2) (*) values was observed between end-diastole and end-systole with T(2) (*) changes of up to approximately 27% over the cardiac cycle which were pronounced in the septum. To conclude, these results underscore the challenges of myocardial T(2) (*) mapping at 7.0 T but demonstrate that these issues can be offset by using tailored shimming techniques and dedicated acquisition schemes

High glucose exposure promotes proliferation and in vivo network formation of adipose-tissue-derived microvascular fragments

High glucose concentrations have been shown to activate endothelial cells and promote angiogenesis. In the present study, it was investigated whether high glucose concentrations could improve the vascularisation capacity of adipose-tissue-derived microvascular fragments (ad-MVF). Ad-MVF were isolated from the epididymal fat pads of donor mice and cultivated for 24 h in University of Wisconsin (UW) solution supplemented with vehicle or 30 mM glucose. Protein expression, morphology, viability and proliferation of the cultivated ad-MVF were analysed by means of proteome profiler mouse angiogenesis array, scanning electron microscopy and immunohistochemistry. Additional cultivated ad-MVF were seeded on to collagen-glycosaminoglycan scaffolds to study their in vivo vascularisation capacity in the dorsal skinfold chamber model by intravital fluorescence microscopy, histology and immunohistochemistry. In vitro, high glucose exposure changed the protein expression pattern of ad-MVF with endoglin, interleukin (IL)-1β and monocyte chemoattractant protein (MCP)-1 as the most up-regulated pro-angiogenic factors. Moreover, high glucose exposure induced the formation of nanopores in the ad-MVF wall. In addition, ad-MVF contained significantly larger numbers of proliferating endothelial and perivascular cells while exhibiting a comparable number of apoptotic cells when compared to vehicle-treated controls. In vivo, scaffolds seeded with high-glucose-exposed ad-MVF exhibited an improved vascularisation and tissue incorporation. These findings demonstrated that the exposure of cultivated ad-MVF to high glucose concentrations is a promising approach to improve their in vivo performance as vascularisation units for tissue engineering and regenerative medicine

Radiographic, Biomechanical and Histological Characterization of Femoral Fracture Healing in Aged CD-1 Mice

With a gradually increasing elderly population, the treatment of geriatric patients represents a major challenge for trauma and reconstructive surgery. Although, it is well established that aging affects bone metabolism, it is still controversial if aging impairs bone healing. Accordingly, we investigated fracture healing in young adult (3–4 months) and aged (16–18 months) CD-1 mice using a stable closed femoral fracture model. Bone healing was analyzed by radiographic, biomechanical and histological analysis at 1, 2, 3, 4 and 5 weeks after fracture. Our results demonstrated an increased callus diameter to femoral diameter ratio in aged animals at later time points of fracture healing when compared to young adult mice. Moreover, our biomechanical analysis revealed a significantly decreased bending stiffness at 3 and 4 weeks after fracture in aged animals. In contrast, at 5 weeks after fracture, the analysis showed no significant difference in bending stiffness between the two study groups. Additional histological analysis showed a delayed endochondral ossification in aged animals as well as a higher amounts of fibrous tissue at early healing time points. These findings indicate a delayed process of callus remodeling in aged CD-1 mice, resulting in a delayed fracture healing when compared to young adult animals. However, the overall healing capacity of the fractured femora was not affected by aging

Efficiency in Multi-objective Games

In a multi-objective game, each agent individually evaluates each overall action-profile on multiple objectives. I generalize the price of anarchy to multi-objective games and provide a polynomial-time algorithm to assess it. This work asserts that policies on tobacco promote a higher economic efficiency

Pantoprazole impairs fracture healing in aged mice

Proton pump inhibitors (PPIs) belong to the most common medication in geriatric medicine. They are known to reduce osteoclast activity and to delay fracture healing in young adult mice. Because differentiation and proliferation in fracture healing as well as pharmacologic actions of drugs markedly differ in the elderly compared to the young, we herein studied the effect of the PPI pantoprazole on bone healing in aged mice using a murine fracture model. Bone healing was analyzed by biomechanical, histomorphometric, radiological and protein biochemical analyses. The biomechanical analysis revealed a significantly reduced bending stiffness in pantoprazole-treated animals when compared to controls. This was associated with a decreased amount of bone tissue within the callus, a reduced trabecular thickness and a higher amount of fibrous tissue. Furthermore, the number of osteoclasts in pantoprazole-treated animals was significantly increased at 2 weeks and decreased at 5 weeks after fracture, indicating an acceleration of bone turnover. Western blot analysis showed a lower expression of the bone morphogenetic protein-4 (BMP-4), whereas the expression of the pro-angiogenic parameters was higher when compared to controls. Thus, pantoprazole impairs fracture healing in aged mice by affecting angiogenic and osteogenic growth factor expression, osteoclast activity and bone formation

Diclofenac, a NSAID, delays fracture healing in aged mice

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, belong to the most prescribed analgesic medication after traumatic injuries. However, there is accumulating evidence that NSAIDs impair fracture healing. Because bone regeneration in aged patients is subject to significant changes in cell differentiation and proliferation as well as a markedly altered pharmacological action of drugs, we herein analyzed the effects of diclofenac on bone healing in aged mice using a stable closed femoral facture model. Thirty-three mice (male n = 14, female n = 19) received a daily intraperitoneal injection of diclofenac (5 mg/kg body weight). Vehicletreated mice (n = 29; male n = 13, female n = 16) served as controls. Fractured mice femora were analyzed by means of X-ray, biomechanics, micro computed tomography (μCT), histology and Western blotting. Biomechanical analyses revealed a significantly reduced bending stiffness in diclofenac-treated animals at 5 weeks after fracture when compared to vehicle-treated controls. Moreover, the callus tissue in diclofenac-treated aged animals exhibited a significantly reduced amount of bone tissue and higher amounts of fibrous tissue. Further histological analyses demonstrated less lamellar bone after diclofenac treatment, indicating a delay in callus remodeling. This was associated with a decreased number of osteoclasts and an increased expression of osteoprotegerin (OPG) during the early phase of fracture healing. These findings indicate that diclofenac delays fracture healing in aged mice by affecting osteogenic growth factor expression and bone formation as well as osteoclast activity and callus remodeling

Making sense of violence risk predictions using clinical notes

Violence risk assessment in psychiatric institutions enables interventions to avoid violence incidents. Clinical notes written by practitioners and available in electronic health records (EHR) are valuable resources that are seldom used to their full potential. Previous studies have attempted to assess violence risk in psychiatric patients using such notes, with acceptable performance. However, they do not explain why classification works and how it can be improved. We explore two methods to better understand the quality of a classifier in the context of clinical note analysis: random forests using topic models, and choice of evaluation metric. These methods allow us to understand both our data and our methodology more profoundly, setting up the groundwork for improved models that build upon this understanding. This is particularly important when it comes to the generalizability of evaluated classifiers to new data, a trustworthiness problem that is of great interest due to the increased availability of new data in electronic format