Search results for: endpoints

Authors: Nathalie Bolding, Marta Montero, Joaquim Cevallos, Juan F. Martin-Lazaro

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Background: Inhaled epoprostenol (iEPO) have been shown to improve PaO2:FiO2 (PF) in combination with bronchodilators (BD). However, there is not an available device to deliver these two therapies concomitantly. We describe a new method to provide this therapy successfully. Objective: To evaluate the response to continuous nebulization of iEPO and intermittent nebulization of Salbutamol/Ipratropium bromide in adults with severe respiratory failure through a double mesh nebulisation in tandem. Methods: This observational study included two mechanical ventilated adults under hourly ventilatory, gasometrical and clinical measurements during 48h. Both had severe respiratory failure treated with continuous iEPO (50 – 200 micrograms/h) and BD (Salbutamol 2.5 mg and Ipratropium bromide 500 mcg every 6 hours) through double mesh nebulisation (Aerogen solo®) placed in tandem in the dry side of the humidificator. The primary endpoints were the variables associated with a positive response to this tandem nebulised therapy (PaFiO2 index, ROX index). Secondary endpoints were laboratory (ABG) clinical and ventilatory variables. Statistical analysis (SPSS v29) included linear regression and ANOVA. Results: The patients included (n=2) survived, both extubated, one after ECMO therapy. Severe acute respiratory failure had a positive response rate to continuous iEPO and intermittent BD: PaFiO2 increased (7.40 to 30.91; P75: 27%) as well as ROX index (2.91 to 11.43; P75: 33%). There was a linear correlation of improvement between iEPO with PaFiO2 (ANOVA, r=0.393, p<0.002) and ROX (r=0.419, p<0.001). iEPO+BD therapy did not show any complications. Conclusion: Continuous and intermittent mesh tandem nebulisation can be effectively delivered with this method with a positive effect in ventilatory parameters without observed complications. Randomised studies will be able to provide reassurance in this new therapy.

Keywords: tandem, mesh, nebulisers, pulmonary, vasoldilators, bronchodilators, respiratory, failure

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Authors: Helmi Temimi

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In this paper, we study the super-convergence properties of the discontinuous Galerkin (DG) method applied to one-dimensional mth-order ordinary differential equations without introducing auxiliary variables. We found that nth−derivative of the DG solution exhibits an optimal O (hp+1−n) convergence rates in the L2-norm when p-degree piecewise polynomials with p≥1 are used. We further found that the odd-derivatives and the even derivatives are super convergent, respectively, at the upwind and downwind endpoints.

Keywords: discontinuous, galerkin, superconvergence, higherorder, error, estimates

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Authors: Mohammad Reza Esmaili

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One of the most important parts of the restoration process of a power network is the synchronizing of its subsystems. In this situation, the biggest concern of the system operators will be the reduction of the standing phase angle (SPA) between the endpoints of the two islands. In this regard, the system operators perform various actions and maneuvers so that the synchronization operation of the subsystems is successfully carried out and the system finally reaches acceptable stability. The most common of these actions include load control, generation control and, in some cases, changing the network topology. Although these maneuvers are simple and common, due to the weak network and extreme load changes, the restoration will be associated with low speed. One of the best ways to control the SPA is to use FACTS devices. By applying a soft control signal, these tools can reduce the SPA between two subsystems with more speed and accuracy, and the synchronization process can be done in less time. Meanwhile, the unified power controller (UPFC), a series-parallel compensator device with the change of transmission line power and proper adjustment of the phase angle, will be the proposed option in order to realize the subject of this research. Therefore, with the optimal placement of UPFC in a power system, in addition to improving the normal conditions of the system, it is expected to be effective in reducing the SPA during power system restoration. Therefore, the presented paper provides an optimal structure to coordinate the three problems of improving the division of subsystems, reducing the SPA and optimal power flow with the aim of determining the optimal location of UPFC and optimal subsystems. The proposed objective functions in this paper include maximizing the quality of the subsystems, reducing the SPA at the endpoints of the subsystems, and reducing the losses of the power system. Since there will be a possibility of creating contradictions in the simultaneous optimization of the proposed objective functions, the structure of the proposed optimization problem is introduced as a non-linear multi-objective problem, and the Pareto optimization method is used to solve it. The innovative technique proposed to implement the optimization process of the mentioned problem is an optimization algorithm called the water cycle (WCA). To evaluate the proposed method, the IEEE 39 bus power system will be used.

Keywords: UPFC, SPA, water cycle algorithm, multi-objective problem, pareto

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Authors: Farzad Masoud Kabir, Jamshid Bagheri, Khosro Barkhordari

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This historical cohort study included 17,751 patients patients who underwent isolated CABG at our center between 2007 and 2016. The endpoints of this study were all-cause mortality and major adverse cardio-cerebrovascular events (MACCEs), comprising acute coronary syndromes, cerebrovascular accidents, and all-cause mortality at five years. Our findings suggest that preoperative obesity (BMI>30 kg/m2) in patients who survive early after CABG is associated with an increased risk of 5-year all-cause mortality and 5-year MACCEs.

Keywords: body mass index, surgical outcomes, midterm, cardiac surgery patients

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Authors: Serge B. Provost, Yishan Zhang

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A moment-based adjustment to the saddlepoint approximation is introduced in the context of density estimation. First applied to univariate distributions, this methodology is extended to the bivariate case. It then entails estimating the density function associated with each marginal distribution by means of the saddlepoint approximation and applying a bivariate adjustment to the product of the resulting density estimates. The connection to the distribution of empirical copulas will be pointed out. As well, a novel approach is proposed for estimating the support of distribution. As these results solely rely on sample moments and empirical cumulant-generating functions, they are particularly well suited for modeling massive data sets. Several illustrative applications will be presented.

Keywords: empirical cumulant-generating function, endpoints identification, saddlepoint approximation, sample moments, density estimation

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Authors: Tuğba Horzum, Ahmet Arikan

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This paper was part of a broader study that investigated what blind students (BSs) understood and how they used concept definitions (CDs) and concept images (CIs) for some mathematical concepts. This paper focused on the polygon concept. For this purpose, four open-ended questions were asked to five blind middle school students. During the interviews, BSs were presented with raised-line materials and were given opportunities to construct geometric shapes with magnetic sticks and micro-balls. Qualitative research techniques applied in grounded theory were used for analyzing documents pictures which were taken from magnetic geometric shapes that BSs constructed, raised-line materials and researcher’s observation notes and interviews. At the end of the analysis, it was observed that BSs used mostly their CIs and never took into account the CDs. Besides, BSs encountered with the difficulties associated with the combination of polygon edges’ endpoints consecutively. Additionally, they focused on the interior of the polygon and the angles which have smaller a size. Lastly, BSs were often conflicted about triangle, rectangle, square and circle whether or not a polygon.

Keywords: blind students, concept definition, concept image, polygon

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Authors: Roberta Pecoraro, Elena Maria Scalisi

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Engineered Nanoparticles (ENPs) and Nanomaterials (ENMs) concern an active research area and a sector in full expansion. They have physical-chemical characteristics and small size that improve their performance compared to common materials. Due to the increase in their production and their subsequent release into the environment, new strategies are emerging to assess risk of nanomaterials. NPs can be released into the environment through aquatic systems by human activities and exert toxicity on living organisms. We evaluated the potential toxic effect of cerium oxide (CeO2) nanoparticles because it’s used in different fields due to its peculiar properties. In order to assess nanoparticles toxicity, Fish Embryo Toxicity (FET) test was performed. Powders of CeO2 NPs supplied by the CNR-IMM of Catania are indicated as CeO2 type 1 (as-prepared) and CeO2 type 2 (modified), while CeO2 type 3 (commercial) is supplied by Sigma-Aldrich. Starting from a stock solution (0.001g/10 ml dilution water) of each type of CeO2 NPs, the other concentration solutions were obtained adding 1 ml of the stock solution to 9 ml of dilution water, leading to three different solutions of concentration (10-4, 10-5, 10-6 g/ml). All the solutions have been sonicated to avoid natural tendency of NPs to aggregate and sediment. FET test was performed according to the OECD guidelines for testing chemicals using our internal protocol procedure. A number of eight selected fertilized eggs were placed in each becher filled with 5 ml of each concentration of the three types of CeO2 NPs; control samples were incubated only with dilution water. Replication was performed for each concentration. During the exposure period, we observed four endpoints (embryo coagulation, lack of formation of somites, failure to lift the yolk bag, no heartbeat) by a stereomicroscope every 24 hours. Immunohistochemical analysis on treated larvae was performed to evaluate the expression of metallothioneins (MTs), Heat Shock Proteins 70 (HSP70) and 7-ethoxyresorufin-O-diethylase (EROD). Our results have not shown evident alterations on embryonic development because all embryos completed the development and the hatching of the eggs, started around the 48th hour after exposure, took place within the last observation at 72 hours. A good reactivity, both in the embryos and in the newly hatched larvae, was found. The presence of heartbeat has also been observed in embryos with reduced mobility confirming their viability. A higher expression of EROD biomarker was observed in the larvae exposed to the three types of CeO2, showing a clear difference with the control. A weak positivity was found for MTs biomarker in treated larvae as well as in the control. HSP70 are expressed homogeneously in all the type of nanoparticles tested but not too much greater than control. Our results are in agreement with other studies in the literature, in which the exposure of Danio rerio larvae to other metal oxide nanoparticles does not show adverse effects on survival and hatching time. Further studies are necessary to clarify the role of these NPs and also to solve conflicting opinions.

Keywords: Danio rerio, endpoints, fish embryo toxicity test, metallic nanoparticles

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Authors: Horia Păunescu

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Purpose: The study aimed to assess the depressant or antidepressant effects of several Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in mice: the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam, and the non-selective COX-1 and COX-2 inhibitors lornoxicam, sodium metamizole, and ketorolac. The current literature data regarding such effects of these agents are scarce. Materials and methods: The study was carried out on NMRI mice weighing 20-35 g, kept in a standard laboratory environment. The study was approved by the Ethics Committee of the University of Medicine and Pharmacy „Carol Davila”, Bucharest. The study agents were injected intraperitoneally, 10 mL/kg body weight (bw) 1 hour before the assessment of the locomotor activity by cage testing (n=10 mice/ group) and 2 hours before the forced swimming tests (n=15). The study agents were dissolved in normal saline (meloxicam, sodium metamizole), ethanol 11.8% v/v in normal saline (ketorolac), or water (lornoxicam), respectively. Negative and positive control agents were also given (amitryptilline in the forced swimming test). The cage floor used in the locomotor activity assessment was divided into 20 equal 10 cm squares. The forced swimming test involved partial immersion of the mice in cylinders (15/9cm height/diameter) filled with water (10 cm depth at 28C), where they were left for 6 minutes. The cage endpoint used in the locomotor activity assessment was the number of treaded squares. Four endpoints were used in the forced swimming test (immobility latency for the entire 6 minutes, and immobility, swimming, and climbing scores for the final 4 minutes of the swimming session), recorded by an observer that was "blinded" to the experimental design. The statistical analysis used the Levene test for variance homogeneity, ANOVA and post-hoc analysis as appropriate, Tukey or Tamhane tests.Results: No statistically significant increase or decrease in the number of treaded squares was seen in the locomotor activity assessment of any mice group. In the forced swimming test, amitryptilline showed an antidepressant effect in each experiment, at the 10 mg/kg bw dosage. Sodium metamizole was depressant at 100 mg/kg bw (increased the immobility score, p=0.049, Tamhane test), but not in lower dosages as well (25 and 50 mg/kg bw). Ketorolac showed an antidepressant effect at the intermediate dosage of 5 mg/kg bw, but not so in the dosages of 2.5 and 10 mg/kg bw, respectively (increased the swimming score, p=0.012, Tamhane test). Meloxicam and lornoxicam did not alter the forced swimming endpoints at any dosage level. Discussion: 1) Certain NSAIDs caused changes in the forced swimming patterns without interfering with locomotion. 2) Sodium metamizole showed a depressant effect, whereas ketorolac proved antidepressant. Conclusion: NSAID-induced mood changes are not class effects of these agents and apparently are independent of the type of inhibited cyclooxygenase (COX-1 or COX-2). Disclosure: This paper was co-financed from the European Social Fund, through the Sectorial Operational Programme Human Resources Development 2007-2013, project number POSDRU /159 /1.5 /S /138907 "Excellence in scientific interdisciplinary research, doctoral and postdoctoral, in the economic, social and medical fields -EXCELIS", coordinator The Bucharest University of Economic Studies.

Keywords: antidepressant, depressant, forced swim, NSAIDs

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Authors: Bhavini Pandya

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This paper considers Hη: T2 → T2 the Perturbed Cerbelli-Giona map. That is a family of 2-dimensional nonlinear area-preserving transformations on the torus T2=[0,1]×[0,1]= ℝ2/ ℤ2. A single parameter η varies between 0 and 1, taking the transformation from a hyperbolic toral automorphism to the “Cerbelli-Giona” map, a system known to exhibit multifractal properties. Here we study the multifractal properties of the family of maps. We apply a box-counting method by defining a grid of boxes Bi(δ), where i is the index and δ is the size of the boxes, to quantify the distribution of stable and unstable manifolds of the map. When the parameter is in the range 0.51< η <0.58 and 0.68< η <1 the map is ergodic; i.e., the unstable and stable manifolds eventually cover the whole torus, although not in a uniform distribution. For accurate numerical results we require correspondingly accurate construction of the stable and unstable manifolds. Here we use the piecewise linearity of the map to achieve this, by computing the endpoints of line segments which define the global stable and unstable manifolds. This allows the generalized fractal dimension Dq, and spectrum of dimensions f(α), to be computed with accuracy. Finally, the intersection of the unstable and stable manifold of the map will be investigated, and compared with the distribution of periodic points of the system.

Keywords: feed forward, gradient descent, neural network, integral equation

Procedia PDF Downloads 152

Authors: Ibrahim Alsendid, Rob Sturman, Benjamin Sharp

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In this paper, we consider a family of 2-dimensional nonlinear area-preserving transformations on the torus. A single parameter η varies between 0 and 1, taking the transformation from a hyperbolic toral automorphism to the “Cerbelli-Giona” map, a system known to exhibit multifractal properties. Here we study the multifractal properties of the family of maps. We apply a box-counting method by defining a grid of boxes Bi(δ), where i is the index and δ is the size of the boxes, to quantify the distribution of stable and unstable manifolds of the map. When the parameter is in the range 0.51< η <0.58 and 0.68< η <1 the map is ergodic; i.e., the unstable and stable manifolds eventually cover the whole torus, although not in a uniform distribution. For accurate numerical results, we require correspondingly accurate construction of the stable and unstable manifolds. Here we use the piecewise linearity of the map to achieve this, by computing the endpoints of line segments that define the global stable and unstable manifolds. This allows the generalized fractal dimension Dq, and spectrum of dimensions f(α), to be computed with accuracy. Finally, the intersection of the unstable and stable manifold of the map will be investigated and compared with the distribution of periodic points of the system.

Keywords: Discrete-time dynamical systems, Fractal geometry, Multifractal behaviour of the Perturbed map, Multifractal of Dynamical systems

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Authors: Peter Fedichev

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We studied fundamental aspects of aging to develop a mathematical model of gene regulatory network. We show that aging manifests itself as an inherent instability of gene network leading to exponential accumulation of regulatory errors with age. To validate our approach we studied age-dependent omic data such as transcriptomes, metabolomes etc. of different model organisms and humans. We build a computational platform based on our model to identify the targets and biomarkers of aging to design new drugs against aging and age-related diseases. As biomarkers of aging, we choose the rate of aging and the biological age since they completely determine the state of the organism. Since rate of aging rapidly changes in response to an external stress, this kind of biomarker can be useful as a tool for quantitative efficacy assessment of drugs, their combinations, dose optimization, chronic toxicity estimate, personalized therapies selection, clinical endpoints achievement (within clinical research), and death risk assessments. According to our model, we propose a method for targets identification for further interventions against aging and age-related diseases. Being a biotech company, we offer a complete pipeline to develop an anti-aging drug-candidate.

Keywords: aging, longevity, biomarkers, senescence

Procedia PDF Downloads 244

Authors: Amy Halseth, Kevin Shan, Kye Gilder, John Buse

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The study assessed the effect of prolonged-release naltrexone 32 mg/bupropion 360 mg (NB) on cardiovascular (CV) events in overweight/obese participants at elevated CV risk. Participants must lose ≥ 2% body weight at 16 wks, without a sustained increase in blood pressure, to continue drug. The study was terminated early after second interim analysis with 50% of all CV events. Data on CV endpoints has been published. Current analyses focus on weight change. Intent-to-treat (ITT) population (placebo [PBO] N=4450, NB N=4455) was 54.5% female, 83.5% white, mean age 61 yrs, mean BMI 37.3 kg/m2; 85.2% had type 2 diabetes, 32.1% had CV disease, 17.4% had both. At 52 wks, ITT-LOCF analysis showed greater least squares mean percent change in weight (LSM%ΔBW) with NB (-3.1%; 95% CI -4.8, -1.4) vs PBO (-0.3%; 95% CI -1.9, 1.4). Both groups demonstrated greater weight loss while on-treatment (NB [-7.3%], PBO [-3.9%]). Odds ratios of 5% and 10% weight loss were 3.3 and 4.1 (ITT-LOCF), respectively, in NB over PBO. At 104 wks, on-treatment LSM%ΔBW was -6.3% with NB (n=1137) vs -3.5% with PBO (n=741). Major reasons for NB withdrawal were adverse events (AE, 29%) and patient decision (21%), with GI disorders being the most common. Weight loss with NB in this study, in an older population predominantly with diabetes and elevated CV risk, was somewhat lower than that observed in overweight/obese participants without diabetes and similar to participants with diabetes in Phase 3 studies.

Keywords: contrave, mysimba, obesity, pharmacotherapy, weight loss

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Authors: Samir Dekali, David Crouzier

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Due to their new physico-chemical properties engineered nanoparticles (ENPs) are increasingly employed in numerous industrial sectors (such as electronics, textile, aerospace, cosmetics, pharmaceuticals, food industry, etc). These new physico-chemical properties can also represent a threat for the human health. Consumers can notably be exposed involuntarily by different routes such as inhalation, ingestion or through the skin. Several studies recently reported a possible biodistribution of these ENPs on the blood-brain barrier (BBB). Consequently, there is a great need for developing BBB in vitro models representative of the in vivo situation and capable of rapidly and accurately assessing ENPs toxic effects and their potential translocation through this barrier. In this study, several in vitro models established with micro-endothelial brain cell lines of different origins (bEnd.3 mouse cell line or a new human cell line) co-cultivated or not with astrocytic cells (C6 rat or C8-B4 mouse cell lines) on Transwells® were compared using different endpoints: trans-endothelial resistance, permeability of the Lucifer yellow and protein junction labeling. Impact of NIST diesel exhaust particles on BBB cell viability is also discussed.

Keywords: nanoparticles, blood-brain barrier, diesel exhaust particles, toxicology

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Authors: Kye Gilder, Kevin Shan, Amy Halseth, Steve Smith

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This study assessed the effect of prolonged-release naltrexone 32 mg/bupropion 360 mg (NB) on cardiovascular (CV) events in overweight/obese participants at elevated CV risk. Participants must lose ≥2% body weight at 16 wks, without a sustained increase in blood pressure, to continue drug. Only serious adverse events (SAE) and adverse events leading to discontinuation of study drug (AELDSD) were collected. The study was terminated early after second interim analysis with 50% of all CV events. Data on CV endpoints has been published. Current analyses focused on AEs in participants on antidepressants at baseline, as these individuals were excluded from Phase 3 trials. Intent-to-treat (ITT) population (placebo [PBO] N=4450, NB N=4455) was 54.5% female, 83.5% white, mean age of 61 yrs, mean BMI 37.3 kg/m2, 22.8% with a history of depression, 23.1% on antidepressants, including 15.4% on an SSRI. SAEs in participants receiving antidepressants was similar between NB (10.7%) and PBO (9.9%) and also similar to overall population (9.5% NB, 8.1% PBO). SAEs in those on SSRIs were similar, 10.1% NB and PBO 9.4%. For those on SSRIs or other antidepressants, AELDSDs were similar to overall population and were primarily GI disorders. Obesity increases the risk of developing depression. For participants taking NB and antidepressants, including SSRIs, there is a similar AE profile as the overall population and data revealed no evidence of an additional health risk with combined use.

Keywords: antidepressant, Contrave, Mysimba, obesity, pharmacotherapy

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Authors: Mohhamed El Habib Labdouni

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Introduction: Co-infection with VIH and tuberculosis poses one of the major ongoing challenges for global TB and AIDS prevention and control. The objective of this study is to raise the issue of the resurgence of TB, in People living with VIH supported in a referent center in western Algeria. Its epidemiological, clinical, biological and radiological new trends, and to compare the mortality rate between early and delayed ART. Methods: It was a prospective study, during 36 months from the 01st/01/2012 to 31st/12/2014, by identifying and analyzing cases of TB-VIH co-infection. Our population was devised in two groups/ early ART and delayed ART. The primary and secondary endpoints were analyzed with Kaplan-Meier curves and log-rank test the period of follow up, which was fixed at 300 weeks. Results: Sixty cases of co-infection TB -VIH were enrolled in our study: 78.3% had pulmonary tuberculosis associated with extra-pulmonary, 13.3% had only pulmonary tuberculosis and 08.3% presented strictly extra-pulmonary TB. The clinical particularity of this co-infection is the frequency of serious localization such us: pleural 23.3%, peritoneal 31.7%, and meningeal suffusion 13.3%.y-.biologicaly we notice the predominance both of pancytopenia and leucoanemia, hyponatremia in 38,6% and hypokalemia in 19,3%. By analyzing Kaplan-Meier survival curves, we notice that early ART initiation is associated with a significant reduction of all-cause mortality (p = 0,000), and we have identified several prognostic factors such as hypokalemia hyponatremia, leukocytosis thrombopenemia leucothrombopenia (p = 0,005). Conclusion: Our study confirms most of the results reported in the literature. Early ART initiation reduces the rate of all-cause mortality, despite the probability of the occurrence of TB-IRIS.

Keywords: TB-HIV co-infection, early ART, hyponatremia, extrapulmonary tuberculosis

Procedia PDF Downloads 155

Authors: Fedili Benamar, Beloulou Mohamed Lamine, Ouahes Hassane, Ghattas Samir

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 Background and aims: Peripheral regional anesthesia has been integrated into most analgesia protocols for total knee arthroplasty which considered among the most painful surgeries with a huge potential for chronicization. The adductor canal block (ACB) has gained popularity. Similarly, the IPACK block has been described to provide analgesia of the posterior knee capsule. This study aimed to evaluate the analgesic efficacy of this block in patients undergoing primary PTG. Methods: 90 patients were randomized to receive either an IPACK, an anterior sciatic block, or a sham block (30 patients in each group + multimodal analgesia and a catheter in the KCA adductor canal). GROUP 1 KCA GROUP 2 KCA+BSA GROUP 3 KCA+IPACK The analgesic blocks were done under echo-guidance preoperatively respecting the safety rules, the dose administered was 20 cc of ropivacaine 0.25% was used. We were to assess posterior knee pain 6 hours after surgery. Other endpoints included quality of recovery after surgery, pain scores, opioid requirements (PCA morphine)(EPI info 7.2 analysis). Results: -groups were matched -A predominance of women (4F/1H). -average age: 68 +/-7 years -the average BMI =31.75 kg/m2 +/- 4. -70% of patients ASA2 ,20% ASA3. -The average duration of the intervention: 89 +/- 19 minutes. -Morphine consumption (PCA) significantly higher in group 1 (16mg) & group 2 (8mg) group 3 (4mg) - The groups were matched . -There was a correlation between the use of the ipack block and postoperative pain Conclusions :In a multimodal analgesic protocol, the addition of IPACK block decreased pain scores and morphine consumption ,

Keywords: regional anesthesia, analgesia, total knee arthroplasty, the adductor canal block (acb), the ipack block, pain

Procedia PDF Downloads 33

Authors: Byung Keun Yang, Jae Eun Ku, Young Seon Joo, Je Sung You, Sung Phil Chung, Hahn Shick Lee

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The purpose of this study is to review the evidence comparing the efficacy and safety between L-carnitine and extracorporeal elimination therapy in the management of acute valproic acid L-carnitine vs Extracorporeal Elimination for Acute Valproic acid Intoxication. PubMed, Embase, Cochrane library, Web of Science, KoreaMed, KMbase, and KISS were searched, using the terms carnitine and valproic acid. All studies, regardless of design, reporting efficacy or safety endpoints were included. Reference citations from identified publications were reviewed. Both English and Korean languages were included. Two authors extracted primary data elements including poisoning severity, presenting features, clinical management, and outcomes. Thirty two articles including 33 cases were identified. Poisoning severity was classified as 3 mild, 11 moderate, and 19 severe cases. Nine cases were treated with L-carnitine while 24 cases received extracorporeal therapy without L-carnitine. All patients except one expired patient treated with hemodialysis recovered clinically and no adverse effects were noted. A case report comparing two patients who ingested the same amount of valproic acid showed increased ICU stay (3 vs. 11 days) in case of delayed extracorporeal therapy. Published evidence comparing L-carnitine with extracorporeal therapy is limited. Based on the available evidence, it is reasonable to consider L-carnitine for patients with acute valproic acid overdose. In case of severe poisoning, extracorporeal therapy would also be considered in the early phase of treatment.

Keywords: carnitine, overdose, poisoning, renal dialysis, valproic acid

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Authors: Nitish Suvarna, Anjali Awasthi

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In an era marked by rapid technological advancements, the integration of Autonomous Vehicles into supply chain networks represents a transformative shift, promising to redefine the paradigms of logistics and transportation. This thesis delves into a comprehensive assessment of the impact of autonomous vehicles on supply chain performance, with a particular focus on network design, operational efficiency, and environmental sustainability. Employing the advanced simulation capabilities of anyLogistix (ALX), the study constructs a digital twin of a conventional supply chain network, encompassing suppliers, production facilities, distribution centers, and customer endpoints. The research methodically integrates Autonomous Vehicles into this intricate network, aiming to unravel the multifaceted effects on transportation logistics including transit times, cost-efficiency, and sustainability. Through simulations and scenarios analysis, the study scrutinizes the operational resilience and adaptability of supply chains in the face of dynamic market conditions and disruptive technologies like Autonomous Vehicles. Furthermore, the thesis undertakes carbon footprint analysis, quantifying the environmental benefits and challenges associated with the adoption of Autonomous Vehicles in supply chain operations. The insights from this research are anticipated to offer a strategic framework for industry stakeholders, guiding the adoption of Autonomous Vehicles to foster a more efficient, responsive, and sustainable supply chain ecosystem. The findings aim to serve as a cornerstone for future research and practical implementations in the realm of intelligent transportation and supply chain management.

Keywords: autonomous vehicle, agri-food supply chain, ALX simulation, anyLogistix

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Authors: Terentes Printzios Dimitrios, Loanna Gourgouli, Vlachopoulos Charalambos

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Aims: Atrial fibrillation (AF) remains one of the major causes of stroke, heart failure, sudden death and cardiovascular morbidity. Ablation techniques are becoming more appealing after the latest results of randomized trials showing the overall clinical benefit. On the other hand, imaging techniques and the frontier application of 3D printing are emerging as a valuable ally for cardiac procedures. However, no randomized trial has directly assessed the impact of preprocedural imaging and especially 3D printing guidance for AF ablation. The present study is designed to investigate for the first time the effect of 3D printing of the heart on the safety and effectiveness of the ablation procedure. Methods and design: The 3D-GALA trial is a randomized, open-label, controlled, multicentre clinical trial of 2 parallel groups designed to enroll a total of 100 patients undergoing ablation using cryo-balloon for paroxysmal and persistent AF. Patients will be randomized with a patient allocation ratio of 1: 1 to preprocedural MRI scan of the heart and 3D printing of left atrium and pulmonary veins and cryoablation versus standard cryoablation without imaging. Patients will be followed up to 6 months after the index procedure. The primary outcome measure is the reduction of radiation dose and contrast amount during pulmonary veins isolation. Secondary endpoints will include the percentage of atrial fibrillation relapse at 24h-Holter electrocardiogram monitoring at 6 months after initial treatment. Discussion: To our knowledge, the 3D-GALA trial will be the first study to provide evidence about the clinical impact of preprocedural imaging and 3D printing before cryoablation.

Keywords: atrial fibrillation, cardiac MRI, cryoablation, 3-d printing

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Authors: S. Shafiee Ardestani, A. Najafi, N. Valizadeh, E. Payani, H. Karimian

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Objectives: Treatment of mild traumatic brain injury in emergency ward patients with any type of traumatic intracranial hemorrhage is flexible. The aim of this study is to assess the clinical outcomes of mild traumatic brain injury patients who had acute traumatic intracranial hemorrhage on initial emergency ward neuroimaging. Materials-Methods: From March 2011 to November 2012 in a retrospective cohort study we enrolled emergency ward patients with mild traumatic brain injury with Glasgow Coma Scale (GCS) scores of 14 or 15 and who had stable vital signs. Patients who had any type of intracranial hemorrhage on first head CT and repeat head CT within 24 hours were included. Patients with initial GCS < 14, injury > 24 hours old, pregnancy, concomitant non-minor injuries, and coagulopathy were excluded. Primary endpoints were neurosurgical procedures and/or death and for discharged patients, return to the emergency ward during one week. Results: Among 755 patients who were referred to the emergency ward and underwent two head CTs during first 24 hours, 302 (40%) were included. The median interval between CT scans was 6 hours (ranging 4 to 8 hours). Consequently, 135 (45%) patients had subarachnoid hemorrhage, 124 (41%) patients had subdural hemorrhage, 15 (5%) patients had epidural hemorrhage, 28 (9%) patients had cerebral contusions, and 54 (18%) patients had intra-parenchymal hemorrhage. Six of 302 patients died within 15 days of injury. 200 patients (66%) have been discharged from the emergency ward, 25 (12%) of whom returned to the emergency ward after one week. Conclusion: Discharge of the head trauma patients after a repeat head CT and brief period of observation in the emergency ward lead to early discharge of mild traumatic brain injury patients with traumatic ICH without adverse events.

Keywords: clinical outcomes, emergency ward, mild traumatic intracranial hemorrhage, Glasgow Coma Scale (GCS)

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Authors: Mahshid Hodjat, Maryam Baeeri, Mohammad Amin Rezvanfar, Mohammad Abdollahi

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Ethephon is one of the most widely used plant growth regulator in agriculture that its application has been increased in recent years. The toxicity of organophosphate compounds is mostly attributed to their potent inhibition of acetylcholinesterase and their involvement in neurodegenerative disease. Although there are few reports on butyrylcholinesterase inhibitory role of ethephon, still there is no evidence on neurotoxicity and genotoxicity of this compound. The aim of the current study is to assess the potential genotoxic effect of ethephon using two genotoxic endpoints; γH2AX expression and comet assay on embryonic murine fibroblast. γH2AX serves as an early and sensitive biomarker for evaluating the genotoxic effects of chemicals. Oxidative stress biomarkers, including intracellular reactive oxygen species, lipid peroxidation and antioxidant capacity were also examined. The results showed a significant increase in cell proliferation 24h post-treatment with 10, 40,160µg/ml ethephon. The γH2AX expression and γH2AX foci count per cell were increased at low concentration of ethephon that was concomitant with increased DNA damage break at 40 and 160 µg/ml as illustrated by increased comet tail moment. A significant increase in lipid peroxidation and ROS formation were observed at 160 µg/ml and higher doses. The results showed that low-dose of ethephon promoted cell proliferation while induce DNA damage, raising the possibility of ethephon mutagenicity. Ethephon-induced genotoxic effect of low dose might not related to oxidative damage. However, ethephon was found to increase oxidative stress at higher doses, lead to cellular cytotoxicity. Taken together, all data indicated that ethylene, deserves more attention as a plant regulator with potential genotoxicity for which appropriate control is needed to reduce its usage.

Keywords: ethephon, DNA damage, γH2AX, oxidative stress

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Authors: Venkat S. Somayajula

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Ground surface temperature history prediction model plays a vital role in determining standards for international nuclear waste management. International standards for borehole based nuclear waste disposal require paleoclimate cycle predictions on scale of a million forward years for the place of waste disposal. This research focuses on developing a paleoclimate cycle prediction model using Bayesian long-short term memory (LSTM) neural architecture operated on accumulated borehole temperature history data. Bayesian models have been previously used for paleoclimate cycle prediction based on Monte-Carlo weight method, but due to limitations pertaining model coupling with certain other prediction networks, Bayesian models in past couldn’t accommodate prediction cycle’s over 1000 years. LSTM has provided frontier to couple developed models with other prediction networks with ease. Paleoclimate cycle developed using this process will be trained on existing borehole data and then will be coupled to surface temperature history prediction networks which give endpoints for backpropagation of LSTM network and optimize the cycle of prediction for larger prediction time scales. Trained LSTM will be tested on past data for validation and then propagated for forward prediction of temperatures at borehole locations. This research will be beneficial for study pertaining to nuclear waste management, anthropological cycle predictions and geophysical features

Keywords: Bayesian long-short term memory neural network, borehole temperature, ground surface temperature history, paleoclimate cycle

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Authors: Mohammad Hossain Mohammadi, Saif Al Ameri, Sana Ziaei, Jinane Mounsef

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Automated enumeration of the number of hand fingers is widely used in several motion gaming and distance control applications, and is discussed in several published papers as a starting block for hand recognition systems. The automated finger enumeration technique should not only be accurate, but also must have a fast response for a moving-picture input. The high performance of video in motion games or distance control will inhibit the program’s overall speed, for image processing software such as Matlab need to produce results at high computation speeds. Since an automated finger enumeration with minimum error and processing time is desired, a comparative study between two finger enumeration techniques is presented and analyzed in this paper. In the pre-processing stage, various image processing functions were applied on a real-time video input to obtain the final cleaned auto-cropped image of the hand to be used for the two techniques. The first technique uses the known morphological tool of skeletonization to count the number of skeleton’s endpoints for fingers. The second technique uses a radial distance method to enumerate the number of fingers in order to obtain a one dimensional hand representation. For both discussed methods, the different steps of the algorithms are explained. Then, a comparative study analyzes the accuracy and speed of both techniques. Through experimental testing in different background conditions, it was observed that the radial distance method was more accurate and responsive to a real-time video input compared to the skeletonization method. All test results were generated in Matlab and were based on displaying a human hand for three different orientations on top of a plain color background. Finally, the limitations surrounding the enumeration techniques are presented.

Keywords: comparative study, hand recognition, fingertip detection, skeletonization, radial distance, Matlab

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Authors: Stephanie Boue, Nicolas Sierro, Julia Hoeng, Manuel C. Peitsch

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Systems biology relies on large numbers of data points and sophisticated methods to extract biologically meaningful signal and mechanistic understanding. For example, analyses of transcriptomics and proteomics data enable to gain insights into the molecular differences in tissues exposed to diverse stimuli or test items. Whereas the interpretation of endpoints specifically measuring a mechanism is relatively straightforward, the interpretation of big data is more complex and would benefit from comparing results obtained with diverse analysis methods. The sbv IMPROVER project was created to implement solutions to verify systems biology data, methods, and conclusions. Computational challenges leveraging the wisdom of the crowd allow benchmarking methods for specific tasks, such as signature extraction and/or samples classification. Four challenges have already been successfully conducted and confirmed that the aggregation of predictions often leads to better results than individual predictions and that methods perform best in specific contexts. Whenever the scientific question of interest does not have a gold standard, but may greatly benefit from the scientific community to come together and discuss their approaches and results, datathons are set up. The inaugural sbv IMPROVER datathon was held in Singapore on 23-24 September 2016. It allowed bioinformaticians and data scientists to consolidate their ideas and work on the most promising methods as teams, after having initially reflected on the problem on their own. The outcome is a set of visualization and analysis methods that will be shared with the scientific community via the Garuda platform, an open connectivity platform that provides a framework to navigate through different applications, databases and services in biology and medicine. We will present the results we obtained when analyzing data with our network-based method, and introduce a datathon that will take place in Japan to encourage the analysis of the same datasets with other methods to allow for the consolidation of conclusions.

Keywords: big data interpretation, datathon, systems toxicology, verification

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Authors: Christos Lampropoulos, Maria Konsta, Vicky Dradaki, Irini Dri, Konstantina Panouria, Tamta Sirbilatze, Ifigenia Apostolou, Vaggelis Lambas, Christina Kordali, Georgios Mavras

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Objectives: Malnutrition in hospitalized patients is related to increased morbidity and mortality. The purpose of our study was to compare various nutritional scores in order to detect the most suitable one for assessing the nutritional status of elderly, hospitalized patients and correlate them with mortality and extension of admission duration, due to patients’ critical condition. Methods: Sample population included 150 patients (78 men, 72 women, mean age 80±8.2). Nutritional status was assessed by Mini Nutritional Assessment (MNA full, short-form), Malnutrition Universal Screening Tool (MUST) and short Nutritional Appetite Questionnaire (sNAQ). Sensitivity, specificity, positive and negative predictive values and ROC curves were assessed after adjustment for the cause of current admission, a known prognostic factor according to previously applied multivariate models. Primary endpoints were mortality (from admission until 6 months afterwards) and duration of hospitalization, compared to national guidelines for closed consolidated medical expenses. Results: Concerning mortality, MNA (short-form and full) and SNAQ had similar, low sensitivity (25.8%, 25.8% and 35.5% respectively) while MUST had higher sensitivity (48.4%). In contrast, all the questionnaires had high specificity (94%-97.5%). Short-form MNA and sNAQ had the best positive predictive value (72.7% and 78.6% respectively) whereas all the questionnaires had similar negative predictive value (83.2%-87.5%). MUST had the highest ROC curve (0.83) in contrast to the rest questionnaires (0.73-0.77). With regard to extension of admission duration, all four scores had relatively low sensitivity (48.7%-56.7%), specificity (68.4%-77.6%), positive predictive value (63.1%-69.6%), negative predictive value (61%-63%) and ROC curve (0.67-0.69). Conclusion: MUST questionnaire is more advantageous in predicting mortality due to its higher sensitivity and ROC curve. None of the nutritional scores is suitable for prediction of extended hospitalization.

Keywords: duration of admission, malnutrition, nutritional assessment scores, prognostic factors for mortality

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Authors: Hui-Chen Tsai, Chien-Jen Ho, Bo-Wei Power Liang, Ying Shen, Yi-Hsin Lai

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Former Taiwan Metal Mining Corporation and its associated 3 wasted flue gas tunnels, hereinafter referred to as 'TMMC', was contaminated with heavy metals, Polychlorinated biphenyls (PCBs) and Total Petroleum Hydrocarbons (TPHs) in soil. Since the contamination had been exposed and unmanaged in the environment for more than 40 years, the extent of the contamination area is estimated to be more than 25 acres. Additionally, TMMC is located in a remote, mountainous area where almost no residents are residing in the 1-km radius area. Thus, it was deemed necessary to conduct an ecological risk assessment in order to evaluate the details of future contaminated site management plan. According to the winter and summer, ecological investigation results, one type of endangered, multiple vulnerable and near threaten plant was discovered, as well as numerous other protected species, such as Crested Serpent Eagle, Crested Goshawk, Black Kite, Brown Shrike, Taiwan Blue Magpie were observed. Ecological soil screening level (Eco-SSLs) developed by USEPA was adopted as a reference to conduct screening assessment. Since all the protected species observed surrounding TMMC site were birds, screening ecological risk assessment was conducted on birds only. The assessment was assessed mainly based on the chemical evaluation, which the contamination in different environmental media was compared directly with the ecological impact levels (EIL) of each evaluation endpoints and the respective hazard quotient (HQ) and hazard index (HI) could be obtained. The preliminary ecological risk assessment results indicated HI is greater than 1. In other words, the biological stressors (birds) were exposed to the contamination, which was already exceeded the dosage that could cause unacceptable impacts to the ecological system. This result was mainly due to the high concentration of arsenic, metal and lead; thus it was suggested the above mention contaminants should be remediated as soon as possible or proper risk management measures should be taken.

Keywords: screening, ecological risk assessment, ecological impact levels, risk management

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Authors: Ibrahim Turfanda, Soniya Rai, Karan Vadher

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Objectives— The study aims to compare real-world adherence to and persistence with dulaglutide and liraglutide in patients with type 2 diabetes (T2D) initiating treatment in UAE. Methods— This was a retrospective, non-interventional study (observation period: 01 March 2017–31 August 2019) using the UAE Dubai e-Claims database. Included: adult patients initiating dulaglutide/liraglutide 01 September 2017–31 August 2018 (index period) with: ≥1 claim for T2D in the 6 months before index date (ID); ≥1 claim for dulaglutide/liraglutide during index period; and continuous medical enrolment for ≥6 months before and ≥12 months after ID. Key endpoints, assessed 3/6/12 months after ID: adherence to treatment (proportion of days covered [PDC; PDC ≥80% considered ‘adherent’], per-group mean±standard deviation [SD] PDC); and persistence (number of continuous therapy days from ID until discontinuation [i.e., >45 days gap] or end of observation period). Patients initiating dulaglutide/liraglutide were propensity score matched (1:1) based on baseline characteristics. Between-group comparison of adherence was analysed using the McNemar test (α=0.025). Persistence was analysed using Kaplan–Meier estimates with log-rank tests (α=0.025) for between-group comparisons. This study presents 12-month outcomes. Results— Following propensity score matching, 263 patients were included in each group. Mean±SD PDC for all patients at 12 months was significantly higher in the dulaglutide versus the liraglutide group (dulaglutide=0.48±0.30, liraglutide=0.39±0.28, p=0.0002). The proportion of adherent patients favored dulaglutide (dulaglutide=20.2%, liraglutide=12.9%, p=0.0302), as did the probability of being adherent to treatment (odds ratio [97.5% CI]: 1.70 [0.99, 2.91]; p=0.03). Proportion of persistent patients also favoured dulaglutide (dulaglutide=15.2%, liraglutide=9.1%, p=0.0528), as did the probability of discontinuing treatment 12 months after ID (p=0.027). Conclusions— Based on the UAE Dubai e-Claims database data, dulaglutide initiators exhibited significantly greater adherence in terms of mean PDC versus liraglutide initiators. The proportion of adherent patients and the probability of being adherent favored the dulaglutide group, as did treatment persistence.

Keywords: adherence, dulaglutide, effectiveness, liraglutide, persistence

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Authors: Emil Sakharov, Alex Zotov, Ilkin Osmanov, Oleg Shelest, Aleksander Troitskiy, Robert Khabazov

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Objective: Since 2015, our center has been actively implementing methods of surgical correction of atrial fibrillation, in particular, in patients with coronary heart disease. The study presents a comparative analysis of the late postoperative period in patients with coronary artery bypass grafting and atrial fibrillation. Methods: The study included 150 patients with ischemic heart disease and atrial fibrillation for the period from 2015 to 2021. Patients were divided into 2 groups. The first group is represented by patients with ischemic heart disease and atrial fibrillation who underwent coronary bypass surgery and surgical correction of atrial fibrillation (N=50). The second group is represented by patients with ischemic heart disease and atrial fibrillation who underwent only myocardial revascularization (N=100). Patients were comparable in age, gender, and initial severity of the condition. Among the patients in group 1 there were 82% were men, while in the second group, their number was 75%. Among the patients of the first group, there were 36% with persistent atrial fibrillation, 20% with long-term persistent atrial fibrillation. In the second group, 10% with persistent atrial fibrillation and 17% with long-term persistent atrial fibrillation. Results: Average follow-up for groups 1 and 2 amounted to 47 months. There were no complications in group 1, such as bleeding and stroke. There was only 1 patient in group 1, who had died from cardiovascular disease. Freedom of atrial fibrillation was in 82% without AADs therapy. In group 2 there were 8 patients who had died from cardiovascular diseases and total freedom of atrial fibrillation was in 35% of patients, among which 42.8% had additional AADs therapy. Follow-up data are presented in Table 2. Progression of heart failure was observed in 3% in group 1 and 7% in group 2. Combined endpoints (recurrence of AF, stroke, progression of heart failure, myocardial infarction) were achieved in 16% in group 1 and 34% in group 2, respectively. Freedom from atrial fibrillation without antiarrhythmic therapy was 82% for group 1 and 35% for group 2. In the first group, there is a more pronounced decrease in heart failure rates. Deaths from cardiovascular causes were recorded in 2% for group 1 and 7% for group 2. Conclusion: Surgical treatment of atrial fibrillation helps to reduce adverse complications in the late postoperative period and contributes to the regression of heart failure.

Keywords: atrial fibrillation, coronary artery bypass grafting, ischaemic heart disease, heart failure

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Authors: Christos Lampropoulos, Maria Konsta, Ifigenia Apostolou, Vicky Dradaki, Tamta Sirbilatze, Irini Dri, Christina Kordali, Vaggelis Lambas, Kostas Argyros, Georgios Mavras

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Objectives: Mediterranean diet has been associated with lower incidence of cardiovascular disease and cancer. The purpose of our study was to examine the hypothesis that Mediterranean diet may protect against mortality and reduce admission duration in elderly, hospitalized patients. Methods: Sample population included 150 patients (78 men, 72 women, mean age 80±8.2). The following data were taken into account in analysis: anthropometric and laboratory data, dietary habits (MedDiet score), patients’ nutritional status [Mini Nutritional Assessment (MNA) score], physical activity (International Physical Activity Questionnaires, IPAQ), smoking status, cause and duration of current admission, medical history (co-morbidities, previous admissions). Primary endpoints were mortality (from admission until 6 months afterwards) and duration of admission, compared to national guidelines for closed consolidated medical expenses. Logistic regression and linear regression analysis were performed in order to identify independent predictors for mortality and admission duration difference respectively. Results: According to MNA, nutrition was normal in 54/150 (36%) of patients, 46/150 (30.7%) of them were at risk of malnutrition and the rest 50/150 (33.3%) were malnourished. After performing multivariate logistic regression analysis we found that the odds of death decreased 30% per each unit increase of MedDiet score (OR=0.7, 95% CI:0.6-0.8, p < 0.0001). Patients with cancer-related admission were 37.7 times more likely to die, compared to those with infection (OR=37.7, 95% CI:4.4-325, p=0.001). According to multivariate linear regression analysis, admission duration was inversely related to Mediterranean diet, since it is decreased 0.18 days on average for each unit increase of MedDiet score (b:-0.18, 95% CI:-0.33 - -0.035, p=0.02). Additionally, the duration of current admission increased on average 0.83 days for each previous hospital admission (b:0.83, 95% CI:0.5-1.16, p<0.0001). The admission duration of patients with cancer was on average 4.5 days higher than the patients who admitted due to infection (b:4.5, 95% CI:0.9-8, p=0.015). Conclusion: Mediterranean diet adequately protects elderly, hospitalized patients against mortality and reduces the duration of hospitalization.

Keywords: Mediterranean diet, malnutrition, nutritional status, prognostic factors for mortality

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Authors: Ifigeneia V. Mavragani, Zacharenia Nikitaki, George Kalantzis, George Iliakis, Alexandros G. Georgakilas

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Complex DNA damage consisting of a combination of DNA lesions, such as Double Strand Breaks (DSBs) and non-DSB base lesions occurring in a small volume is considered as one of the most important biological endpoints regarding ionizing radiation (IR) exposure. Strong theoretical (Monte Carlo simulations) and experimental evidence suggests an increment of the complexity of DNA damage and therefore repair resistance with increasing linear energy transfer (LET). Experimental detection of complex (clustered) DNA damage is often associated with technical deficiencies limiting its measurement, especially in cellular or tissue systems. Our groups have recently made significant improvements towards the identification of key parameters relating to the efficient detection of complex DSBs and non-DSBs in human cellular systems exposed to IR of varying quality (γ-, X-rays 0.3-1 keV/μm, α-particles 116 keV/μm and 36Ar ions 270 keV/μm). The induction and processing of DSB and non-DSB-oxidative clusters were measured using adaptations of immunofluorescence (γH2AX or 53PB1 foci staining as DSB probes and human repair enzymes OGG1 or APE1 as probes for oxidized purines and abasic sites respectively). In the current study, Relative Biological Effectiveness (RBE) values for DSB and non-DSB induction have been measured in different human normal (FEP18-11-T1) and cancerous cell lines (MCF7, HepG2, A549, MO59K/J). The experimental results are compared to simulation data obtained using a validated microdosimetric fast Monte Carlo DNA Damage Simulation code (MCDS). Moreover, this simulation approach is implemented in two realistic clinical cases, i.e. prostate cancer treatment using X-rays generated by a linear accelerator and a pediatric osteosarcoma case using a 200.6 MeV proton pencil beam. RBE values for complex DNA damage induction are calculated for the tumor areas. These results reveal a disparity between theory and experiment and underline the necessity for implementing highly precise and more efficient experimental and simulation approaches.

Keywords: complex DNA damage, DNA damage simulation, protons, radiotherapy

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