The Combination of Amoxicillin-Clavulanic Acid and Ketoconazole in the Treatment of Madurella mycetomatis Eumycetoma and Staphylococcus aureus Co-infection

Eumycetoma is a chronic progressive disabling and destructive inflammatory disease which is commonly caused by the fungus Madurella mycetomatis. It is characterized by the formation of multiple discharging sinuses. It is usually treated by antifungal agents but it is assumed that the therapeutic efficiency of these agents is reduced by the co-existence of Staphylococcus aureus co-infection developing in these sinuses. This prospective study was conducted to investigate the safety, efficacy and clinical outcome of combined antibiotic and antifungal therapy in eumycetoma patients with superimposed Staphylococcus aureus infection. The study enrolled 337 patients with confirmed M. mycetomatis eumycetoma and S. aureus co-infection. Patients were allocated into three groups; 142 patients received amoxicillin-clavulanic acid and ketoconazole, 93 patients received ciprofloxacin and ketoconazole and 102 patients received ketoconazole only. The study showed that, patients who received amoxicillin-clavulanic acid and ketoconazole treatment had an overall better clinical outcome compared to those who had combined ciprofloxacin and ketoconazole or to those who received ketoconazol

Guided wave-based characterisation of cracks in pipes utilising approximate Bayesian computation

Available online 29 August 2023This paper proposed a probabilistic framework of damage characterisation to detect and identify early-state cracks in pipe-like structures using ultrasonic guided waves. The crack location, crack sizes (e.g., depth and width of the crack), and Young’s modulus are considered as unknown parameters in the model updating using a Bayesian approach, by which their values and the associated uncertainties are quantified. The proposed framework is developed based on approximate Bayesian computation (ABC) by subset simulation, which is a likelihood-free Bayesian approach. This algorithm estimates the posterior distributions of unknown parameters by directly accessing the similarity between the measured signals from experiments and the simulated guided wave (GW) signals from the numerical model. In this case, the evaluation of likelihood functions can be smartly circumvented during Bayesian inference. A time-domain spectral finite element (SFE) method with a cracked finite element model is employed to model the pipes to enhance the computational efficiency of the simulation and model updating. Numerical and experimental case studies are carried out to evaluate the performance of the proposed likelihood-free approach. Numerical results show the accuracy and robustness of the proposed approach in identifying unknown parameters under different scenarios. The associated uncertainties of each parameter are also quantified by analysing the statistical properties of the sample set, such as mean and coefficient of variation (COV) values. Experimental results show that the proposed method can accurately identify the unknown parameters, which further verifies the accuracy and practicability of the probabilistic damage characterisation framework.Zijie Zeng, Min Gao, Ching Tai Ng, Abdul Hamid Sheik

Fourier Method for Approximating Eigenvalues of Indefinite Stekloff Operator

We introduce an efficient method for computing the Stekloff eigenvalues associated with the Helmholtz equation. In general, this eigenvalue problem requires solving the Helmholtz equation with Dirichlet and/or Neumann boundary condition repeatedly. We propose solving the related constant coefficient Helmholtz equation with Fast Fourier Transform (FFT) based on carefully designed extensions and restrictions of the equation. The proposed Fourier method, combined with proper eigensolver, results in an efficient and clear approach for computing the Stekloff eigenvalues.Comment: 12 pages, 4 figure

Kontsevich product and gauge invariance

We analyze the question of $U_{\star} (1)$ gauge invariance in a flat non-commutative space where the parameter of non-commutativity, $\theta^{\mu\nu} (x)$, is a local function satisfying Jacobi identity (and thereby leading to an associative Kontsevich product). We show that in this case, both gauge transformations as well as the definitions of covariant derivatives have to modify so as to have a gauge invariant action. We work out the gauge invariant actions for the matter fields in the fundamental and the adjoint representations up to order $\theta^{2}$ while we discuss the gauge invariant Maxwell theory up to order $\theta$. We show that despite the modifications in the gauge transformations, the covariant derivative and the field strength, Seiberg-Witten map continues to hold for this theory. In this theory, translations do not form a subgroup of the gauge transformations (unlike in the case when $\theta^{\mu\nu}$ is a constant) which is reflected in the stress tensor not being conserved.Comment: 7 page

Teleparallel Gravity and Dimensional Reductions of Noncommutative Gauge Theory

We study dimensional reductions of noncommutative electrodynamics on flat space which lead to gauge theories of gravitation. For a general class of such reductions, we show that the noncommutative gauge fields naturally yield a Weitzenbock geometry on spacetime and that the induced diffeomorphism invariant field theory can be made equivalent to a teleparallel formulation of gravity which macroscopically describes general relativity. The Planck length is determined in this setting by the Yang-Mills coupling constant and the noncommutativity scale. The effective field theory can also contain higher-curvature and non-local terms which are characteristic of string theory. Some applications to D-brane dynamics and generalizations to include the coupling of ordinary Yang-Mills theory to gravity are also described.Comment: 31 pages LaTeX; References adde

Time-Space Noncommutativity in Gravitational Quantum Well scenario

A novel approach to the analysis of the gravitational well problem from a second quantised description has been discussed. The second quantised formalism enables us to study the effect of time space noncommutativity in the gravitational well scenario which is hitherto unavailable in the literature. The corresponding first quantized theory reveals a leading order perturbation term of noncommutative origin. Latest experimental findings are used to estimate an upper bound on the time--space noncommutative parameter. Our results are found to be consistent with the order of magnitude estimations of other NC parameters reported earlier.Comment: 7 pages, revTe

Diagnostic yield of rare skeletal dysplasia conditions in the radiogenomics era

Background Skeletal dysplasia (SD) conditions are rare genetic diseases of the skeleton, encompassing a heterogeneous group of over 400 disorders, and represent approximately 5% of all congenital anomalies. Developments in genetic and treatment technologies are leading to unparalleled therapeutic advances; thus, it is more important than ever to molecularly confirm SD conditions. Data on ‘rates-of-molecular yields’ in SD conditions, through exome sequencing approaches, is limited. Figures of 39% and 52.5% have been reported in the USA (n = 54) and South Korea (n = 185) respectively. Methods We discuss a single-centre (in the UK) experience of whole-exome sequencing (WES) in a cohort of 15 paediatric patients (aged 5 months to 12 years) with SD disorders previously molecularly unconfirmed. Our cohort included patients with known clinical diagnoses and undiagnosed skeletal syndromes. Extensive phenotyping and expert radiological review by a panel of international SD radiology experts, coupled with a complex bioinformatics pipeline, allowed for both gene-targeted and gene-agnostic approaches. Results Significant variants leading to a likely or confirmed diagnosis were identified in 53.3% (n = 8/15) of patients; 46.7% (n = 7/15) having a definite molecular diagnosis and 6.7% (n = 1/15) having a likely molecular diagnosis. We discuss this in the context of a rare disease in general and specifically SD presentations. Of patients with known diagnoses pre-WES (n = 10), molecular confirmation occurred in 7/10 cases, as opposed to 1/5 where a diagnosis was unknown pre-test. Thus, diagnostic return is greatest where the diagnosis is known pre-test. For WGS (whole genome sequencing, the next iteration of WES), careful case selection (ideally of known diagnoses pre-test) will yield highest returns. Conclusions Our results highlight the cost-effective use of WES-targeted bioinformatic analysis as a diagnostic tool for SD, particularly patients with presumed SD, where detailed phenotyping is essential. Thorough co-ordinated clinical evaluation between clinical, radiological, and molecular teams is essential for improved yield and clinical care. WES (and WGS) yields will increase with time, allowing faster diagnoses, avoiding needless investigations, ensuring individualised patient care and patient reassurance. Further diagnoses will lead to increased information on natural history/mechanistic details, and likely increased therapies and clinical trials

Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts

Background To identify in vivo new cardiac binding sites of serum response factor (SRF) in genes and to study the response of these genes to mild over-expression of SRF, we employed a cardiac-specific, transgenic mouse model, with mild over-expression of SRF (Mild-O SRF Tg). Methodology Microarray experiments were performed on hearts of Mild-O-SRF Tg at 6 months of age. We identified 207 genes that are important for cardiac function that were differentially expressed in vivo. Among them the promoter region of 192 genes had SRF binding motifs, the classic CArG or CArG-like (CArG-L) elements. Fifty-one of the 56 genes with classic SRF binding sites had not been previously reported. These SRF-modulated genes were grouped into 12 categories based on their function. It was observed that genes associated with cardiac energy metabolism shifted toward that of carbohydrate metabolism and away from that of fatty acid metabolism. The expression of genes that are involved in transcription and ion regulation were decreased, but expression of cytoskeletal genes was significantly increased. Using public databases of mouse models of hemodynamic stress (GEO database), we also found that similar altered expression of the SRF-modulated genes occurred in these hearts with cardiac ischemia or aortic constriction as well. Conclusion and significance SRF-modulated genes are actively regulated under various physiological and pathological conditions. We have discovered that a large number of cardiac genes have classic SRF binding sites and were significantly modulated in the Mild-O-SRF Tg mouse hearts. Hence, the mild elevation of SRF protein in the heart that is observed during typical adult aging may have a major impact on many SRF-modulated genes, thereby affecting Cardiac structure and performance. The results from our study could help to enhance our understanding of SRF regulation of cellular processes in the aged heart

Quantum Gravity, Field Theory and Signatures of Noncommutative Spacetime

A pedagogical introduction to some of the main ideas and results of field theories on quantized spacetimes is presented, with emphasis on what such field theories may teach us about the problem of quantizing gravity. We examine to what extent noncommutative gauge theories may be regarded as gauge theories of gravity. UV/IR mixing is explained in detail and we describe its relations to renormalization, to gravitational dynamics, and to deformed dispersion relations in models of quantum spacetime of interest in string theory and in doubly special relativity. We also discuss some potential experimental probes of spacetime noncommutativity.Comment: 26 pages, 4 figures; v2: comments and references added; v3: typos corrected, clarifying comments and references added; Based on Plenary Lecture delivered at the XXIX Encontro Nacional de Fisica de Particulas e Campos, Sao Lourenco, Brasil, September 22-26, 2008; Final version to be published in General Relativity and Gravitatio