75 research outputs found

    The contact electrogram and its architectural determinants in atrial fibrillation

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    The electrogram is the sine qua non of excitable tissues, yet classification in atrial fibrillation (AF) remains poorly related to substrate factors. The objective of this thesis was to establish the relationship between electrograms and two commonly implicated substrate factors, connexin 43 and fibrosis in AF. The substrates and methods chosen to achieve this ranged from human acutely induced AF using open chest surgical mapping (Chapter 6), ex vivo whole heart Langendorff (Chapter 7) with in vivo telemetry confirming spontaneous AF in a new species of rat, the Brown Norway and finally isolated atrial preparations from an older cohort of rats using orthogonal pacing and novel co-localisation methods at sub-millimetre resolution and in some atria, optical mapping (Chapter 8). In rodents, electrode size and spacing was varied (Chapters 5, 10) to study its effects on structure function correlations (Chapter 9). Novel indices of AF organisation and automated electrogram morphology were used to quantify function (Chapter 4). Key results include the discoveries that humans without any history of prior AF have sinus rhythm electrograms with high spectral frequency content, that wavefront propagation velocities correlated with fibrosis and connexin phosphorylation ratios, that AF heterogeneity of conduction correlates to fibrosis and that orthogonal pacing in heavily fibrosed atria causes anisotropy in electrogram-fibrosis correlations. Furthermore, fibrosis and connexin 43 have differing and distinct spatial resolutions in their relationship with AF organisational indices. In conclusion a new model of AF has been found, and structure function correlations shown on an unprecedented scale, but with caveats of electrode size and direction dependence. These findings impact structure function methods and prove the effect of substrate on AF organisation.Open Acces

    Sentinel node localisation using pre-operative lymphoscintigraphy and intraoperative gamma probe in early oral cavity cancer

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    Objectives: To assess the diagnostic value of sentinel lymph node localisation using pre-operative lymphoscintigraphy and intra-operative gamma probe radio localisation in Pakistani patients suffering from early stage squamous cell carcinoma of the oral cavity.Methods: The prospective case series was conducted between September 2007 and April 2010 at the Aga Khan University Hospital, Karachi. It comprised patients with T1and T2 oral cavity cancer with clinically and radiologically negative neck. Pre-operative lymphoscintigraphy was performed one day before surgery and intra-operative gamma probe was used to detect sentinel node. Final histo-pathological evaluation was taken as the gold standard.Results: The study comprised 42 patients: 32(76%) males and 10(24%) females. The primary tumour site was buccal mucosa in 25 (60%) patients, and tongue in 17 (40%). Sentinel lymph node was detected in 38 (90%) patients.On final histopathological identification, 7 (17%) patients had cancer in the neck nodes. In all patients with metastasis, sentinel lymph node technique correctly identified the involved neck level. None of the patients revealed metastasis in non-sentinel lymph nodes.Conclusion: Evidence suggested the use of sentinel node biopsy in patients with head and neck squamous cell carcinoma

    Future Directions for Mapping Atrial Fibrillation

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    Mapping for AF focuses on the identification of regions of interest that may guide management and – in particular – ablation therapy. Mapping may point to specific mechanisms associated with localised scar or fibrosis, or electrical features, such as localised repetitive, rotational or focal activation. In patients in whom AF is caused by disorganised waves with no spatial predilection, as proposed in the multiwavelet theory for AF, mapping would be of less benefit. The role of AF mapping is controversial at the current time in view of the debate over the underlying mechanisms. However, recent clinical expansions of mapping technologies confirm the importance of understanding the state of the art, including limitations of current approaches and potential areas of future development

    An Application of Artificial Intelligence for the Joint Estimation of Amplitude and Two-Dimensional Direction of Arrival of Far Field Sources Using 2-L-Shape Array

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    An easy and efficient approach, based on artificial intelligence technique, is proposed to jointly estimate the amplitude, elevation, and azimuth angles of far field sources impinging on 2-L-shape array. In these proposed artificial intelligence techniques, the metaheuristics based on genetic algorithm and simulated annealing are used as global optimizers assisted with rapid local version of pattern search for optimization of the adaptive parameters. The performance metric is employed on a fitness evaluation function depending on mean square error which is optimum and requires single snapshot to converge. The proposed approaches are easy to understand, and simple to implement; the genetic algorithm specifically hybridized with pattern search generates fairly good results. The comparison of the given schemes is carried out with 1-L-shape array, as well as, with parallel-shape array and is found to be in good agreement in terms of accuracy, convergence rate, computational complexity, and mean square error. The effectiveness and efficiency of the given schemes are examined through Monte Carlo simulations and their inclusive statistical analysis

    Knowledge, attitudes, and practices of the general population of Pakistan regarding typhoid conjugate vaccine: findings of a cross-sectional study

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    Typhoid fever, a common enteric disease in Pakistan, caused by Salmonella typhi, is becoming an extended drug-resistant organism and is preventable through the typhoid conjugate vaccine (TCV). Public adherence to preventive measures is influenced by knowledge and attitude toward the vaccine. This study investigates the knowledge, attitudes, and practices of the general population of Pakistan toward TCV. The differences in mean scores and factors associated with typhoid conjugate vaccine knowledge, attitudes, and practices were investigated. A total of 918 responses were received with a mean age of 25.9 ± 9.6, 51% were women, and 59.6% had graduation-level education. The majority of them responded that vaccines prevent illness (85.3%) and decrease mortality and disability (92.6%), and typhoid could be prevented by vaccination (86.7%). In total, 77.7 and 80.8% considered TCV safe and effective, respectively. Of 389 participants with children, 53.47% had vaccinated children, according to the extended program on immunization (EPI). Higher family income has a higher odds ratio (OR) for willingness toward booster dose of TCV [crude odds ratio (COR) = 4.920, p–value <0.01; adjusted odds ratio (aOR) = 2.853, value of p <0.001], and negative attitude regarding the protective effect of TCV has less willingness toward the booster dose with statistical significance (COR = 0.388, value of p = 0.017; aOR = 0.198, value of p = 0.011). The general population of Pakistan had a good level of knowledge about the benefits of TCV, and attitude and practices are in favor of the usage of TCV. However, a few religious misconceptions are prevalent in public requiring the efforts to overcome them to promote the usage of vaccines to prevent the disease and antibiotic resistance

    Inguinal lymph node metastases from a testicular seminoma: a case report and a review of the literature

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    <p>Abstract</p> <p>Introduction</p> <p>We report the case of a true hermaphrodite with testicular seminoma with resulting metastases to the inguinal lymph nodes eight months after radical orchidectomy. This is an unusual presentation of testicular cancer and, to the best of our knowledge, the first report of this kind in the literature.</p> <p>Case presentation</p> <p>A 45-year-old Caucasian true hermaphrodite, raised as a male, developed a testicular seminoma. He had undergone a left orchidopexy at the age of 10 for undescended testes. Metastases from testicular tumors to inguinal lymph nodes are a rare occurrence. It has been suggested that previous inguinal or scrotal surgery may alter the pattern of nodal metastasis of testicular cancer. We review the literature to evaluate the incidence of inguinal lymph node involvement in early stage testicular cancer and discuss possible routes of metastases to this unusual site. We also discuss the management of the inguinal lymph nodes in patients with testicular tumors and a previous history of inguinal or scrotal surgery, as this remains controversial.</p> <p>Conclusion</p> <p>Inguinal lymph node metastases from testicular cancer are rare. A history of inguinal or scrotal surgery may predispose involvement of the inguinal nodes. During radical inguinal orchidectomy, the surgeon should be careful to minimize the handling of the testis and ensure high ligation of the spermatic cord up to the internal inguinal ring to reduce the risk of inguinal lymph node metastasis.</p

    Deep eutectic solvent coated cerium oxide nanoparticles based polysulfone membrane to mitigate environmental toxicology

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    In this study, ceria nanoparticles (NPs) and deep eutectic solvent (DES) were synthesized, and the ceria-NP’s surfaces were modified by DES to form DES-ceria NP filler to develop mixed matrix membranes (MMMs). For the sake of interface engineering, MMMs of 2%, 4%, 6% and 8% filler loadings were fabricated using solution casting technique. The characterizations of SEM, FTIR and TGA of synthesized membranes were performed. SEM represented the surface and cross-sectional morphology of membranes, which indicated that the filler is uniformly dispersed in the polysulfone. FTIR was used to analyze the interaction between the filler and support, which showed there was no reaction between the polymer and DES-ceria NPs as all the peaks were consistent, and TGA provided the variation in the membrane materials with respect to temperature, which categorized all of the membranes as very stable and showed that the trend of stability increases with respect to DES-ceria NPs filler loading. For the evaluation of efficiency of the MMMs, the gas permeation was tested. The permeability of CO2 was improved in comparison with the pristine Polysulfone (PSF) membrane and enhanced selectivities of 35.43 (αCO2/CH4) and 39.3 (αCO2/N2) were found. Hence, the DES-ceria NP-based MMMs proved useful in mitigating CO2 from a gaseous mixture

    Estimates, trends, and drivers of the global burden of type 2 diabetes attributable to PM2.5 air pollution, 1990-2019 : an analysis of data from the Global Burden of Disease Study 2019

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    Background Experimental and epidemiological studies indicate an association between exposure to particulate matter (PM) air pollution and increased risk of type 2 diabetes. In view of the high and increasing prevalence of diabetes, we aimed to quantify the burden of type 2 diabetes attributable to PM2.5 originating from ambient and household air pollution.Methods We systematically compiled all relevant cohort and case-control studies assessing the effect of exposure to household and ambient fine particulate matter (PM2.5) air pollution on type 2 diabetes incidence and mortality. We derived an exposure-response curve from the extracted relative risk estimates using the MR-BRT (meta-regression-Bayesian, regularised, trimmed) tool. The estimated curve was linked to ambient and household PM2.5 exposures from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, and estimates of the attributable burden (population attributable fractions and rates per 100 000 population of deaths and disability-adjusted life-years) for 204 countries from 1990 to 2019 were calculated. We also assessed the role of changes in exposure, population size, age, and type 2 diabetes incidence in the observed trend in PM2.5-attributable type 2 diabetes burden. All estimates are presented with 95% uncertainty intervals.Findings In 2019, approximately a fifth of the global burden of type 2 diabetes was attributable to PM2.5 exposure, with an estimated 3.78 (95% uncertainty interval 2.68-4.83) deaths per 100 000 population and 167 (117-223) disability-adjusted life-years (DALYs) per 100 000 population. Approximately 13.4% (9.49-17.5) of deaths and 13.6% (9.73-17.9) of DALYs due to type 2 diabetes were contributed by ambient PM2.5, and 6.50% (4.22-9.53) of deaths and 5.92% (3.81-8.64) of DALYs by household air pollution. High burdens, in terms of numbers as well as rates, were estimated in Asia, sub-Saharan Africa, and South America. Since 1990, the attributable burden has increased by 50%, driven largely by population growth and ageing. Globally, the impact of reductions in household air pollution was largely offset by increased ambient PM2.5.Interpretation Air pollution is a major risk factor for diabetes. We estimated that about a fifth of the global burden of type 2 diabetes is attributable PM2.5 pollution. Air pollution mitigation therefore might have an essential role in reducing the global disease burden resulting from type 2 diabetes. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe

    Estimates, trends, and drivers of the global burden of type 2 diabetes attributable to PM2.5 air pollution, 1990-2019 : An analysis of data from the Global Burden of Disease Study 2019

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    Background Experimental and epidemiological studies indicate an association between exposure to particulate matter (PM) air pollution and increased risk of type 2 diabetes. In view of the high and increasing prevalence of diabetes, we aimed to quantify the burden of type 2 diabetes attributable to PM2·5 originating from ambient and household air pollution. Methods We systematically compiled all relevant cohort and case-control studies assessing the effect of exposure to household and ambient fine particulate matter (PM2·5) air pollution on type 2 diabetes incidence and mortality. We derived an exposure–response curve from the extracted relative risk estimates using the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. The estimated curve was linked to ambient and household PM2·5 exposures from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, and estimates of the attributable burden (population attributable fractions and rates per 100 000 population of deaths and disability-adjusted life-years) for 204 countries from 1990 to 2019 were calculated. We also assessed the role of changes in exposure, population size, age, and type 2 diabetes incidence in the observed trend in PM2·5-attributable type 2 diabetes burden. All estimates are presented with 95% uncertainty intervals. Findings In 2019, approximately a fifth of the global burden of type 2 diabetes was attributable to PM2·5 exposure, with an estimated 3·78 (95% uncertainty interval 2·68–4·83) deaths per 100 000 population and 167 (117–223) disability-adjusted life-years (DALYs) per 100 000 population. Approximately 13·4% (9·49–17·5) of deaths and 13·6% (9·73–17·9) of DALYs due to type 2 diabetes were contributed by ambient PM2·5, and 6·50% (4·22–9·53) of deaths and 5·92% (3·81–8·64) of DALYs by household air pollution. High burdens, in terms of numbers as well as rates, were estimated in Asia, sub-Saharan Africa, and South America. Since 1990, the attributable burden has increased by 50%, driven largely by population growth and ageing. Globally, the impact of reductions in household air pollution was largely offset by increased ambient PM2·5. Interpretation Air pollution is a major risk factor for diabetes. We estimated that about a fifth of the global burden of type 2 diabetes is attributable PM2·5 pollution. Air pollution mitigation therefore might have an essential role in reducing the global disease burden resulting from type 2 diabetes
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