Novel Identification of LYVE-1 Positive Macrophages in Rheumatoid Synovial Tissue

Objective: LYVE-1+ macrophages are observed in a range of cancers, where they play a role in tumour lymphangiogenesis. In rheumatoid arthritis (RA), lymphangiogenesis increases in the early stage of the disease and decreases as it progresses, potentially exacerbating inflammatory cell persistence. We investigated whether LYVE-1+ macrophages were present in RA synovium. Methods: Synovial tissue from RA patients was obtained at joint replacement surgery and immunohistochemistry was performed to visualise LYVE-1+ and CD68+ cells. Results: LYVE-1+ macrophages were present in rheumatoid synovial tissue, the first observation of this kind. Conclusion: Despite the reduction in lymphangiogenesis in chronic RA, LYVE-1 positive macrophages are present and there is a potential role for macrophages in the generation of lymphatic vessels

Synopsis of an engineering solution for a painful problem Phantom Limb Pain

This paper is synopsis of a recently proposed solution for treating patients who suffer from Phantom Limb Pain (PLP). The underpinning approach of this research and development project is based on an extension of “mirror box” therapy which has had some promising results in pain reduction. An outline of an immersive individually tailored environment giving the patient a virtually realised limb presence, as a means to pain reduction is provided. The virtual 3D holographic environment is meant to produce immersive, engaging and creative environments and tasks to encourage and maintain patients’ interest, an important aspect in two of the more challenging populations under consideration (over-60s and war veterans). The system is hoped to reduce PLP by more than 3 points on an 11 point Visual Analog Scale (VAS), when a score less than 3 could be attributed to distraction alone

Tissue drives lesion: computational evidence of interspecies variability in cardiac radiofrequency ablation

Radiofrequency catheter ablation (RFCA) is widely used for the treatment of various types of cardiac arrhythmias. Typically, the efficacy and the safety of the ablation protocols used in the clinics are derived from tests carried out on animal specimens, including swines. However, these experimental findings cannot be immediately translated to clinical practice on human patients, due to the difference in the physical properties of the types of tissue. Computational models can assist in the quantification of this variability and can provide insights in the results of the RFCA for different species. In this work, we consider a standard ablation protocol of 10g force, 30W power for 30s. We simulate its application on a porcine cardiac tissue, a human ventricle and a human atrium. Using a recently developed computational model that accounts for the mechanical properties of the tissue, we explore the onset and the growth of the lesion along time by tracking its depth and width, and we compare the lesion size and dimensions at the end of the ablation

Lagrangian Reachabililty

We introduce LRT, a new Lagrangian-based ReachTube computation algorithm that conservatively approximates the set of reachable states of a nonlinear dynamical system. LRT makes use of the Cauchy-Green stretching factor (SF), which is derived from an over-approximation of the gradient of the solution flows. The SF measures the discrepancy between two states propagated by the system solution from two initial states lying in a well-defined region, thereby allowing LRT to compute a reachtube with a ball-overestimate in a metric where the computed enclosure is as tight as possible. To evaluate its performance, we implemented a prototype of LRT in C++/Matlab, and ran it on a set of well-established benchmarks. Our results show that LRT compares very favorably with respect to the CAPD and Flow* tools.Comment: Accepted to CAV 201

Sharper and Simpler Nonlinear Interpolants for Program Verification

Interpolation of jointly infeasible predicates plays important roles in various program verification techniques such as invariant synthesis and CEGAR. Intrigued by the recent result by Dai et al.\ that combines real algebraic geometry and SDP optimization in synthesis of polynomial interpolants, the current paper contributes its enhancement that yields sharper and simpler interpolants. The enhancement is made possible by: theoretical observations in real algebraic geometry; and our continued fraction-based algorithm that rounds off (potentially erroneous) numerical solutions of SDP solvers. Experiment results support our tool's effectiveness; we also demonstrate the benefit of sharp and simple interpolants in program verification examples

Mitochondrial dysfunction in sepsis is associated with diminished intramitochondrial TFAM despite its increased cellular expression

Sepsis is characterized by a dysregulated immune response, metabolic derangements and bioenergetic failure. These alterations are closely associated with a profound and persisting mitochondrial dysfunction. This however occurs despite increased expression of the nuclear-encoded transcription factor A (TFAM) that normally supports mitochondrial biogenesis and functional recovery. Since this paradox may relate to an altered intracellular distribution of TFAM in sepsis, we tested the hypothesis that enhanced extramitochondrial TFAM expression does not translate into increased intramitochondrial TFAM abundance. Accordingly, we prospectively analyzed PBMCs both from septic patients (n = 10) and lipopolysaccharide stimulated PBMCs from healthy volunteers (n = 20). Extramitochondrial TFAM protein expression in sepsis patients was 1.8-fold greater compared to controls (p = 0.001), whereas intramitochondrial TFAM abundance was approximate 80% less (p < 0.001). This was accompanied by lower mitochondrial DNA copy numbers (p < 0.001), mtND1 expression (p < 0.001) and cellular ATP content (p < 0.001) in sepsis patients. These findings were mirrored in lipopolysaccharide stimulated PBMCs taken from healthy volunteers. Furthermore, TFAM-TFB2M protein interaction within the human mitochondrial core transcription initiation complex, was 74% lower in septic patients (p < 0.001). In conclusion, our findings, which demonstrate a diminished mitochondrial TFAM abundance in sepsis and endotoxemia, may help to explain the paradox of lacking bioenergetic recovery despite enhanced TFAM expression

Positive Semidefiniteness and Positive Definiteness of a Linear Parametric Interval Matrix

We consider a symmetric matrix, the entries of which depend linearly on some parameters. The domains of the parameters are compact real intervals. We investigate the problem of checking whether for each (or some) setting of the parameters, the matrix is positive definite (or positive semidefinite). We state a characterization in the form of equivalent conditions, and also propose some computationally cheap sufficient\,/\,necessary conditions. Our results extend the classical results on positive (semi-)definiteness of interval matrices. They may be useful for checking convexity or non-convexity in global optimization methods based on branch and bound framework and using interval techniques

Synopsis of an engineering solution for a painful problem: Phantom limb pain

This paper is synopsis of a recently proposed solution for treating patients who suffer from Phantom Limb Pain (PLP). The underpinning approach of this research and development project is based on an extension of "mirror box" therapy which has had some promising results in pain reduction. An outline of an immersive individually tailored environment giving the patient a virtually realised limb presence, as a means to pain reduction is provided. The virtual 3D holographic environment is meant to produce immersive, engaging and creative environments and tasks to encourage and maintain patients' interest, an important aspect in two of the more challenging populations under consideration (over-60s and war veterans). The system is hoped to reduce PLP by more than 3 points on an 11 point Visual Analog Scale (VAS), when a score less than 3 could be attributed to distraction alone. Copyright © 2014 SCITEPRESS - Science and Technology Publications. All rights reserved.Published versio