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Background: The aim of this study was to evaluate the effectiveness of positron emission tomography/computed tomography with [18 F]-fludeoxyglucose (FDG-PET/CT) and radiomics analysis in detecting differences between the native aorta and the abdominal aortic allograft after the total eradication of infection in patients undergoing infected graft removal and in situ reconstruction with cryopreserved allografts. Methods: Between January 2008 and December 2018, 56 vascular reconstructions with allografts have been performed at our department. The present series included 12 patients undergoing abdominal aortic in situ reconstruction with cryopreserved allografts. During the follow-up, all patients underwent a total-body [18 F]FDG PET/CT with subsequent radiomics analysis. In all patients, a comparative analysis between the data extracted from native aorta and cryopreserved graft for each patient was performed. Results: All patients were male with a mean age of 72.8 years (range 63–84). Mean duration of follow-up was 51.3 months (range 3–120). During the follow-up, 2 patients (16.7%) needed a redo allograft-related surgical intervention. Overall, the rate of allograft dilatation was 33.3%. No patient had a redo infection during the follow-up. Radiomics analysis showed a different signature of implanted allograft and native aorta. Comparative analysis between the native aortas and cryopreserved allografts (dilated or not) showed several statistical differences for many texture features. Conclusions: The higher metabolic activity of allografts could indicate a state of immune-mediated degeneration. This theory should be proven with prospective, multicentric studies with larger sample sizes.

Purpose of Review: Cardiovascular infections are serious disease associated with high morbidity and mortality. Their diagnosis is challenging, requiring a proper management for a prompt recognition of the clinical manifestations, and a multidisciplinary approach involving cardiologists, cardiothoracic surgeons, infectious diseases specialist, imagers, and microbiologists. Imaging plays a central role in the diagnostic workout, including molecular imaging techniques. In this setting, two different strategies might be used to image infections: the first is based on the use of agents targeting the microorganism responsible for the infection. Alternatively, we can target the components of the pathophysiological changes of the inflammatory process and/or the host response to the infectious pathogen can be considered. Understanding the strength and limitations of each strategy is crucial to select the most appropriate imaging tool. Recent Findings: Currently, multislice computed tomography (MSCT) and nuclear imaging (18F-fluorodeoxyglucose positron emission tomography/computed tomography, and leucocyte scintigraphy) are part of the diagnostic strategies. The main role of nuclear medicine imaging (PET/CT and SPECT/CT) is the confirmation of valve/CIED involvement and/or associated perivalvular infection and the detection of distant septic embolism. Proper patients’ preparation, imaging acquisition, and reconstruction as well as imaging reading are crucial to maximize the diagnostic information. Summary: In this manuscript, we described the use of molecular imaging techniques, in particular WBC imaging, in patients with infective endocarditis, cardiovascular implantable electronic device infections, and infections of composite aortic graft, underlying the strength and limitations of such approached as compared to the other imaging modalities.

Infective endocarditis is associated with high morbidity and mortality. Early diagnosis is crucial for adequate patient's management, as early treatment improves the prognosis. Hardly diagnosed on the basis of a single symptom, sign or diagnostic test. Rather, the diagnosis requires a multidisciplinary discussion in addition to the integration of clinical signs, microbiology data and imaging data. The application of multimodality imaging, including molecular imaging techniques has improved the sensitivity to detect IE, also allowing for early detection of septic emboli and metastatic infections before these become clinically apparent. In this chapter, we will describe the main epidemiological, clinical and diagnostic challenges in IE with particular regard to the role of WBC SPECT/CT. In addition, the needs of proper hybrid equipment, dedicated imaging acquisition protocols, specific expertise for imaging reading and imaging interpretations in this field are discussed, emphasizing the need of a specific reference framework within a Cardiovascular Multidisciplinary Team Approach.

Cardiovascular (CVS) infections are associated with high morbidity and mortality. Early diagnosis is crucial for adequate patient's management, as early treatment improves the prognosis. Hardly they are diagnosed on the basis of a single symptom, sign or diagnostic test, being a multidisciplinary discussion in addition to the integration of clinical signs, microbiology data and imaging data necessary in many cases. The application of multimodality imaging, including molecular imaging techniques has improved the sensitivity to detect infections involving heart valves and vessels and implanted cardiovascular devices while also allowing for early detection of septic emboli and metastatic infections before these become clinically apparent. In this chapter, we describe the role of WBC SPECT/CT and [18F] FDG PET/CT in most clinically relevant CVS infections including dedicated imaging acquisition protocols, specific imaging reading and interpretations criteria, emphasizing the need of a specific reference framework within a Cardiovascular Multidisciplinary Team Approach to select the best test or combination of tests for each specific clinical situation.

We present a study of the fast, spontaneous rotation regime of tearing modes (TM) in the RFX-mod circular tokamak discharges. Integrated analyses of magnetic, flow and kinetic measurements, are discussed. This analysis of rotation frequency components related to the ion flow and diamagnetic drift shows that the TM fast rotation is mainly driven by the diamagnetic drift. The global decrease of the temperature profile, induced by a growing mode amplitude, can explain the slowing-down of the rotation, which in turn can trigger a potentially disruptive sequence. We show that in RFX-mod the slowing-down cannot be explained solely on the basis of the electromagnetic torque with the external conductive structures, as often reported in literature from other experiments. This analysis, indeed, suggests a strong relationship between the TM dynamics and the transport physics. Statistical analysis of disruptions with slowing down of island rotation shows that TMs take a part in the disruption, even without a locking to the wall.

The results are presented of an experimental activity performed in the RFX-mod device aimed at characterizing plasma dynamics in the so-called Ultralow-q (ULq) magnetic configuration, which corresponds to edge safety factor values below 1. The role of the edge safety factor in determining plasma dynamics is studied. In particular, a characterization of MHD activity is performed. The results of dedicated non-linear 3D visco-resistive MHD simulations are in good quantitative agreement with the experimental observations. In particular, the predicted tendency for ULq plasmas to be characterized by magnetic spectra dominated by a single mode (either a kink or a double resonant internal mode) is confirmed by experiment. Magnetic reconnection plays a relevant role in determining the dynamics of the magnetic topology. Both almost quiescent and largely fluctuating plasmas are observed with a strong sensitivity on the edge safety factor. The main MHD properties of the ULq are compared to those of RFP and tokamak discharges, also produced in the RFX-mod device. MHD modes exhibit toroidal rotation at a frequency depending on mode amplitude. Differently from what encountered in RFP plasmas at comparable current levels, no wall locking is detected.

Coordination of cell behaviour is key to a myriad of biological processes including tissue morphogenesis, wound healing, and tumour growth. As such, individual-based computational models, which explicitly describe inter-cellular interactions, are commonly used to model collective cell dynamics. However, when using individual-based models, it is unclear how descriptions of cell boundaries affect overall population dynamics. In order to investigate this we define three cell boundary descriptions of varying complexities for each of three widely used off-lattice individual-based models: overlapping spheres, Voronoi tessellation, and vertex models. We apply our models to multiple biological scenarios to investigate how cell boundary description can influence tissue-scale behaviour. We find that the Voronoi tessellation model is most sensitive to changes in the cell boundary description with basic models being inappropriate in many cases. The timescale of tissue evolution when using an overlapping spheres model is coupled to the boundary description. The vertex model is demonstrated to be the most stable to changes in boundary description, though still exhibits timescale sensitivity. When using individual-based computational models one should carefully consider how cell boundaries are defined. To inform future work, we provide an exploration of common individual-based models and cell boundary descriptions in frequently studied biological scenarios and discuss their benefits and disadvantages.

Wound healing is a complex process occurring across multiple temporal and spatial scales. In this thesis we use individual-based computational and mathematical models to explore the epidermal re-epithelialisation stage of wound healing. We focus specifically on the overlapping spheres, Voronoi tessellation and vertex dynamics models in two dimensions and the computational choices available for each model that may impact healing dynamics. We find that the overlapping spheres and Voronoi tessellation models are highly sensitive to model choice, whereas the vertex dynamics model is insensitive to model choice. Therefore, we use the vertex dynamics model to investigate six re-epithelialisation mechanisms in small, acute wounds: cell compression, proliferation, cell edge contractility, the purse-string mechanism, cell crawling in response to local cues and cell crawling towards a point source. The scale of the mechanism can affect not only the time scale of re-epithelialisation, but also the shape of the wound over time. The most significant mechanisms for larger wounds are cell proliferation and crawling in response to local cues. We incorporate these mechanisms into a model of a larger wound to study the interplay between cell migration and proliferation during re-epithelialisation. Drawbacks of the individual-based approach include the computational costs and limited mathematical frameworks for model analysis. Hence, we convert our two-dimensional individual-based model of a larger wound into a one-dimensional model and derive a partial differential equation continuum approximation that can provide further insights into the re-epithelialisation process. From the one-dimensional model we can investigate the relationship between mechanical relaxation and tissue growth and derive an upper bound on tissue growth over time. We conclude that increasing the amount of cell proliferation or migration alone is insufficient to promote re-epithelialisation and that there is an in

Pain is an alarm mechanism to prevent body damage in response to noxious stimuli. The nerve growth factor (NGF)/TrkA axis plays an essential role as pain mediator, and several clinical trials using antibodies against NGF have yielded promising results, but side effects have precluded their clinical approval. A better understanding of the mechanism of NGF/TrkA-mediated nociception is needed. Here, we find that ARMS/Kidins220, a scaffold protein for Trk receptors, is a modulator of nociception. Male mice, with ARMS/Kidins220 reduction exclusively in TrkA-expressing cells, displayed hyperalgesia to heat, inflammatory, and capsaicin stimuli, but not to cold or mechanical stimuli. Simultaneous deletion of brain-derived neurotrophic factor (BDNF) reversed the effects of ARMS/Kidins220 knock down alone. Mechanistically, ARMS/Kidins220 levels are reduced in vitro and in vivo in response to capsaicin through calpains, and this reduction leads to enhanced regulated BDNF secretion from dorsal root ganglion. Altogether, these data indicate that ARMS/Kidins220 protein levels have a role as a pain modulator in the NGF/TrkA axis regulating BDNF secretion.