Search results for: Genevieve Pugh
33 Membrane Spanning DNA Origami Nanopores for Protein Translocation
Authors: Genevieve Pugh, Johnathan Burns, Stefan Howorka
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Single-molecule sensing via protein nanopores has achieved a step-change in portable and label-free DNA sequencing. However, protein pores of both natural or engineered origin are not able to produce the tunable diameters needed for effective protein sensing. Here, we describe a generic strategy to build synthetic DNA nanopores that are wide enough to accommodate folded protein. The pores are composed of interlinked DNA duplexes and carry lipid anchors to achieve the required membrane insertion. Our demonstrator pore has a contiguous cross-sectional channel area of 50 nm2 which is 6-times larger than the largest protein pore. Consequently, transport of folded protein across bilayers is possible. The modular design is amenable for different pore dimensions and can be adapted for protein sensing or to create molecular gates in synthetic biology.Keywords: biosensing, DNA nanotechnology, DNA origami, nanopore sensing
Procedia PDF Downloads 32432 Effects of Oral L-Carnitine on Liver Functions after Trans arterial Chemoembolization in Hepatocellular Carcinoma Patients
Authors: Ali Kassem, Aly Taha, Abeer Hassan, Kazuhide Higuchi
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Introduction: Trans arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) is usually followed by hepatic dysfunction that limits its efficacy. L-carnitine is recently studied as hepatoprotective agent. Our aim is to evaluate the L-carnitine effects against the deterioration of liver functions after TACE. Method: 53 patients with intermediate stage HCC were assigned into two groups; L-carnitine group (26 patients) who received L-carnitine 300 mg tablet twice daily from 2 weeks before to 12 weeks after TACE and control group (27 patients) without L-carnitine therapy. 28 of studied patients received branched chain amino acids granules. Results: There were significant differences between L-carnitine Vs. control group in mean serum albumin change from baseline to 1 week and 4 weeks after TACE (p < 0.05). L-Carnitine maintained Child-Pugh score at 1 week after TACE and exhibited improvement at 4 weeks after TACE (p < 0.01 Vs 1 week after TACE). Control group has significant Child-Pugh score deterioration from baseline to 1 week after TACE (p < 0.05) and 12 weeks after TACE (p < 0.05). There were significant differences between L-carnitine and control groups in mean Child-Pugh score change from baseline to 4 weeks (p < 0.05) and 12 weeks after TACE (p < 0.05). L-carnitine displayed improvement in (PT) from baseline to 1 week, 4 w (p < 0.05) and 12 weeks after TACE. PT in control group declined less than baseline along all follow up intervals. Total bilirubin in L-carnitine group decreased at 1 week post TACE while in control group, it significantly increased at 1 week (p = 0.01). ALT and C-reactive protein elevation were suppressed at 1 week after TACE in Lcarnitine group. The hepatoprotective effects of L-carnitine were enhanced by concomitant use of branched chain amino acids. Conclusion: L-carnitine and BCAA combination therapy offer a novel supportive strategy after TACE in HCC patients.Keywords: hepatocellular carcinoma, L-carnitine, liver functions , trans-arterial embolization
Procedia PDF Downloads 15531 An Analytical Study on the Effect of Chronic Liver Disease Severity and Etiology on Lipid Profiles
Authors: Thinakar Mani Balusamy, Venkateswaran A. R., Bharat Narasimhan, Ratnakar Kini S., Kani Sheikh M., Prem Kumar K., Pugazhendi Thangavelu, Arun Murugan, Sibi Thooran Karmegam, Radhakrishnan N., Mohammed Noufal, Amit Soni
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Background and Aims: The liver is integral to lipid metabolism, and a compromise in its function leads to perturbations in these pathways. In this study, we hope to determine the correlation between CLD severity and its effect on lipid parameters. We also look at the etiology-specific effects on lipid levels. Materials and Methods: This is a retrospective cross-sectional analysis of 250 patients with cirrhosis compared to 250 healthy age and sex-matched controls. Severity assessment of CLD using MELD and Child-Pugh scores was performed and etiological details collected. A questionnaire was used to obtain patient demographic details and lastly, a fasting lipid profile (Total, LDL, HDL cholesterol, Triglycerides and VLDL) was obtained. Results: All components of the lipid profile declined linearly with increasing severity of CLD as determined by MELD and Child-Pugh scores. Lipid levels were clearly lower in CLD patients as compared to healthy controls. Interestingly, preliminary analysis indicated that CLD of different etiologies had differential effects on Lipid profiles. This aspect is under further analysis. Conclusion: All components of the lipid profile were definitely lower in CLD patients as compared to controls and demonstrated an inverse correlation with increasing severity. The utilization of this parameter as a prognosticating aid requires further study. Additionally, preliminary analysis indicates that various CLD etiologies appear to have specific effects on the lipid profile – a finding under further analysis.Keywords: CLD, cholesterol, HDL, LDL, lipid profile, triglycerides, VLDL
Procedia PDF Downloads 22130 Elastic and Thermal Behaviour of LaX (X= Cd, Hg) Intermetallics: A DFT Study
Authors: Gitanjali Pagare, Hansa Devi, S. P. Sanyal
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Full-potential linearized augmented plane wave (FLAPW) method has been employed within the generalized gradient approximation (GGA) and local spin density approximation (LSDA) as the exchange correlation potential to investigate elastic properties of LaX (X = Cd and Hg) in their B2-type (CsCl) crystal structure. The calculated ground state properties such as lattice constant (a0), bulk modulus (B) and pressure derivative of bulk modulus (B') agree well with the available experimental results. The second order elastic constants (C11, C12 and C44) have been calculated. The ductility or brittleness of these intermetallic compounds is predicted by using Pugh’s rule B/GH and Cauchy’s pressure (C12-C44). The calculated results indicate that LaHg is the ductile whereas LaCd is brittle in nature.Keywords: ductility/brittleness, elastic constants, equation of states, FP-LAPW method, intermetallics
Procedia PDF Downloads 44629 Sexualization of Women in Nigerian Magazine Advertisements
Authors: Kehinde Augustina Odukoya
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This study examines the portrayal of women in Nigerian magazine advertisements, with the aim to investigate whether there is sexualization of women in the advertisements. To achieve this aim, content analyses of 61 magazine advertisements from 5 different categories of magazines; a general interest magazine (Genevieve), fashion magazine (Hints Complete Fashion), men’s magazine (Mode), women’s magazine (Totally Whole) and a relationship magazine (Forever) were carried out. Erving Goffman’s 1979 frame analysis and Kang’s two additional coding categories were used to investigate the sexualization of women. Findings show that women are used for decorative purposes and objectified in over 70 per cent of the advertisements analyzed. Also, there is sexualization of women in magazine advertisements because women are nude 57.4 percent of the magazine advertisements.Keywords: advertisements, magazine, sexualization, women
Procedia PDF Downloads 36528 Thermal Modelling and Experimental Comparison for a Moving Pantograph Strip
Authors: Nicolas Delcey, Philippe Baucour, Didier Chamagne, Geneviève Wimmer, Auditeau Gérard, Bausseron Thomas, Bouger Odile, Blanvillain Gérard
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This paper proposes a thermal study of the catenary/pantograph interface for a train in motion. A 2.5D complex model of the pantograph strip has been defined and created by a coupling between a 1D and a 2D model. Experimental and simulation results are presented and with a comparison allow validating the 2.5D model. Some physical phenomena are described and presented with the help of the model such as the stagger motion thermal effect, particular heats and the effect of the material characteristics. Finally it is possible to predict the critical thermal configuration during a train trip.Keywords: electro-thermal studies, mathematical optimizations, multi-physical approach, numerical model, pantograph strip wear
Procedia PDF Downloads 32827 Mathematical Modelling of the Effect of Glucose on Pancreatic Alpha-Cell Activity
Authors: Karen K. Perez-Ramirez, Genevieve Dupont, Virginia Gonzalez-Velez
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Pancreatic alpha-cells participate on glucose regulation together with beta cells. They release glucagon hormone when glucose level is low to stimulate gluconeogenesis from the liver. As other excitable cells, alpha cells generate Ca2+ and metabolic oscillations when they are stimulated. It is known that the glucose level can trigger or silence this activity although it is not clear how this occurs in normal and diabetic people. In this work, we propose an electric-metabolic mathematical model implemented in Matlab to study the effect of different glucose levels on the electrical response and Ca2+ oscillations of an alpha cell. Our results show that Ca2+ oscillations appear in opposite phase with metabolic oscillations in a window of glucose values. The model also predicts a direct relationship between the level of glucose and the intracellular adenine nucleotides showing a self-regulating pathway for the alpha cell.Keywords: Ca2+ oscillations, mathematical model, metabolic oscillations, pancreatic alpha cell
Procedia PDF Downloads 17926 A Medical Resource Forecasting Model for Emergency Room Patients with Acute Hepatitis
Authors: R. J. Kuo, W. C. Cheng, W. C. Lien, T. J. Yang
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Taiwan is a hyper endemic area for the Hepatitis B virus (HBV). The estimated total number of HBsAg carriers in the general population who are more than 20 years old is more than 3 million. Therefore, a case record review is conducted from January 2003 to June 2007 for all patients with a diagnosis of acute hepatitis who were admitted to the Emergency Department (ED) of a well-known teaching hospital. The cost for the use of medical resources is defined as the total medical fee. In this study, principal component analysis (PCA) is firstly employed to reduce the number of dimensions. Support vector regression (SVR) and artificial neural network (ANN) are then used to develop the forecasting model. A total of 117 patients meet the inclusion criteria. 61% patients involved in this study are hepatitis B related. The computational result shows that the proposed PCA-SVR model has superior performance than other compared algorithms. In conclusion, the Child-Pugh score and echogram can both be used to predict the cost of medical resources for patients with acute hepatitis in the ED.Keywords: acute hepatitis, medical resource cost, artificial neural network, support vector regression
Procedia PDF Downloads 42325 Application of Global Predictive Real Time Control Strategy to Improve Flooding Prevention Performance of Urban Stormwater Basins
Authors: Shadab Shishegar, Sophie Duchesne, Genevieve Pelletier
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Sustainability as one of the key elements of Smart cities, can be realized by employing Real Time Control Strategies for city’s infrastructures. Nowadays Stormwater management systems play an important role in mitigating the impacts of urbanization on natural hydrological cycle. These systems can be managed in such a way that they meet the smart cities standards. In fact, there is a huge potential for sustainable management of urban stormwater and also its adaptability to global challenges like climate change. Hence, a dynamically managed system that can adapt itself to instability of the environmental conditions is desirable. A Global Predictive Real Time Control approach is proposed in this paper to optimize the performance of stormwater management basins in terms of flooding prevention. To do so, a mathematical optimization model is developed then solved using Genetic Algorithm (GA). Results show an improved performance at system-level for the stormwater basins in comparison to static strategy.Keywords: environmental sustainability, optimization, real time control, storm water management
Procedia PDF Downloads 17924 European Refugee Camps and the Right to an Adequate Standard of Living: Advancing Accountability under International Human Rights Law
Authors: Genevieve Zingg
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Since the onset of the 2015 ‘refugee crisis’ in the European Union (EU), migrant deaths have overwhelmingly occurred in the Mediterranean Sea. However, far less attention has been paid to the startling number of injuries, deaths, and allegations of systematic human rights violations occurring within European refugee camps. Most troubling is the assertion that injuries and deaths in EU refugee camps have occurred as a result of negligent management and poor access to healthcare, food, water and sanitation, and other elements that comprise an adequate standard of living under international human rights law. Using available evidence and documentation, this paper will conduct a thorough examination of the causes of death and injury in EU refugee camps, with a specific focus on Greece, in order to identify instances of negligence or conditions that amount to potential breaches of human rights law. Based on its analysis, this paper will subsequently explore potential legal avenues to achieving justice and accountability under international human rights law in order to effectively address and remedy inadequate standards of living causing wrongful death or injury in European refugee camps.Keywords: European Union, Greece, human rights, international human rights law, migration, refugees
Procedia PDF Downloads 19523 Women's Cyber Intimate Partner Violence Victimization
Authors: Mylène Fernet, Geneviève Brodeur, Martine Hébert
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Background: The growth of information and communication technologies has led to an increase in the prevalence of cyber intimate partner violence among women in early adulthood. However, there is a lack of research addressing the intervention needs of women who have been victims of cyber intimate partner violence. This qualitative study aimed to identify the knowledge, resources, and tools that women require to better respond to such violence. Methodology: Semi-structured individual interviews and four online discussion groups were conducted with 28 Canadian women aged 18 to 29 who had experienced cyber intimate partner violence by a romantic or intimate partner or an ex-partner. The data were analyzed using thematic analysis. Findings: The key elements identified suggest that women need information to help them recognize the signs and varied forms of cyber intimate partner violence, particularly those that are more nuanced and harder to detect. Furthermore, participants emphasized the importance of having access to both online and offline support to aid in their recovery from cyber intimate partner violence. Additionally, the women's narratives also highlighted their need for resources on how to protect themselves from cyber intimate partner violence. Conclusion: Based on the findings from this study, it is essential to develop prevention and intervention strategies for cyber intimate partner violence that address these knowledge gaps, provide support options, and offer prevention tools tailored to adult women.Keywords: women, cyberviolence, intimate partner violence, prevention strategies
Procedia PDF Downloads 2322 The Mandaya Woman: Her Role as Balyan (Priestess) and Magdadawot (Bard)
Authors: Genevieve Jorolan-Quintero
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After the devastation caused by typhoon Haiyan in the southeastern part of the Philippines in 2012, there was this intense need among the indigenous communities to ‘reconcile’ with nature. The belief that the deluge, which claimed thousands of lives, was caused by the destruction of the environment because of humanities’ greed and carelessness was widespread and strong. The rift had to be mended. Nature had to be appeased. For this, the balyan (priestess) was called in to perform a ritual. Only she can communicate with the spirits. The communities depend on her spiritual intervention as she alone has the power to invoke the spirits of nature. Among the indigenous people, the balyan is most often also a magdadawot (bard) who possesses the knowledge especially about the folk epics and the skill to chant them. The balyan is the communities’ repository of knowledge. When one passes away, a whole library of tribal knowledge and wisdom is lost. The oral traditions embody the life values, ideals, customs, and even the history of the First Nations People. These include the myths, epics, legends, riddles, and songs. The indigenous system is patriarchal, but is actually indirectly matriarchal reflecting the authority of the woman. Disputes within the community are heard and tried by the Council of Elders. However, the balyan is often consulted for her opinion. Her advice is deemed significant and most often necessary. These are three instances that highlight the significant role of the balyan among the indigenous communities in the Philippines, especially among the Mandaya tribe who live in the southern region of the country. This paper highlights the unique kind of leadership of the Mandaya woman – as priestess and bard - and her impact on the lives of her people.Keywords: balyan, bard, magdadawot, mandaya
Procedia PDF Downloads 33421 Victims and Violators: Open Source Information, Admissibility Standards, and War Crimes Investigations in Iraq and Syria
Authors: Genevieve Zingg
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Modern technology and social media platforms have fundamentally altered the nature of war crimes investigations by providing new forms of data, evidence, and documentation, and pose a unique opportunity to expand the efficacy of international law. However, much of the open source information available is deemed inadmissible in subsequent legal proceedings and fails to function as evidence largely due to issues of reliability and verifiability. Focusing on current judicial investigations related to ongoing conflicts in Syria and Iraq, this paper will examine key challenges and opportunities for the effective use of open source information in securing justice. This paper will consider strategies and approaches that can be used to ensure that information collected by affected populations meets basic admissibility standards. This paper argues that the critical failure to equip civilian populations in conflict zones with knowledge and information regarding established admissibility standards and guidelines both jeopardizes the potential of open source information and compromises the ability of victims to participate effectively in justice and accountability processes. The ultimate purpose of this paper is, therefore, to examine how to maximize the value of open source information based on the rules of evidence in international, regional, and national courts, and how to maximize the participation of affected populations in holding their abusers to account.Keywords: human rights, international criminal law, international justice, international law, Iraq, open source information, social media, Syria, transitional justice, war crimes
Procedia PDF Downloads 33720 Effect of Depth on Texture Features of Ultrasound Images
Authors: M. A. Alqahtani, D. P. Coleman, N. D. Pugh, L. D. M. Nokes
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In diagnostic ultrasound, the echo graphic B-scan texture is an important area of investigation since it can be analyzed to characterize the histological state of internal tissues. An important factor requiring consideration when evaluating ultrasonic tissue texture is the depth. The effect of attenuation with depth of ultrasound, the size of the region of interest, gain, and dynamic range are important variables to consider as they can influence the analysis of texture features. These sources of variability have to be considered carefully when evaluating image texture as different settings might influence the resultant image. The aim of this study is to investigate the effect of depth on the texture features in-vivo using a 3D ultrasound probe. The left leg medial head of the gastrocnemius muscle of 10 healthy subjects were scanned. Two regions A and B were defined at different depth within the gastrocnemius muscle boundary. The size of both ROI’s was 280*20 pixels and the distance between region A and B was kept constant at 5 mm. Texture parameters include gray level, variance, skewness, kurtosis, co-occurrence matrix; run length matrix, gradient, autoregressive (AR) model and wavelet transform were extracted from the images. The paired t –test was used to test the depth effect for the normally distributed data and the Wilcoxon–Mann-Whitney test was used for the non-normally distributed data. The gray level, variance, and run length matrix were significantly lowered when the depth increased. The other texture parameters showed similar values at different depth. All the texture parameters showed no significant difference between depths A and B (p > 0.05) except for gray level, variance and run length matrix (p < 0.05). This indicates that gray level, variance, and run length matrix are depth dependent.Keywords: ultrasound image, texture parameters, computational biology, biomedical engineering
Procedia PDF Downloads 29819 The Anti-Obesity Effects of the Aqueous and Ethanolic Leaf Extracts of Blumea balsamifera on Diet-Induced Obese Sprague-Dawley Rats
Authors: Mae Genevieve G. Cheung, Michael G. Cuevas, Lovely Fe L. Cuison, Elijin P. Dai, Katrina Marie S. Duron, Azalea Damaris E. Encarnacion, May T. Magtoto, Gina C. Castro
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The present study aims to evaluate the effectiveness of aqueous and ethanolic leaf extracts of Blumea balsamifera in reducing obesity on diet-induced obese Sprague-Dawley rats. Aqueous and ethanolic leaf extracts were obtained by maceration and percolation, respectively, of air-dried, grinded leaves. The test animals were given a high fat diet (HFD) for 21 days, except for one negative control group fed with a standard diet (SD). The Blumea balsamifera extracts were given at doses of 300 mg/Kg and 600 mg/Kg for BBAE and BBEE groups, and the positive control group, Orlistat, was given at 21.6 mg/Kg dose. After 24 days of treatment, the statistical difference of parameters such as Lee’s index and lipid profile of each group before and after the treatment period were determined separately using Tukey’s test of two-way Analysis of Variance (ANOVA). The statistical results showed that the600mg/kg dose of BBAE and BBEE had greatly lowered the Lee’s index among the other doses while the 300 mg/Kg dose BBEE, 600 mg/Kg BBAE, and 300 mg/kg BBAE lowered the total cholesterol level, LDL level, and VLDL and total triglyceride level respectively. The extracts, however, lowered the HDL level which was also exhibited by the standard drug, Orlistat.Keywords: adipocytes, adipogenesis, Blumea balsamifera, Lee’s index, obesity, Sambong
Procedia PDF Downloads 37718 Building Collapse: Factors and Resisting Mechanisms: A Review of Case Studies
Authors: Genevieve D. Fernandes, Nisha P. Naik
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All through the ages in all human civilizations, men have been engaged in construction activity, not only to build their dwellings and house their activities, but also roads, bridges to facilitate means of transport, and communication etc. The main concern in this activity was to ensure safety and reduce the collapse of the buildings and other structures. But even after taking all precautions, it is impossible to guarantee safety and collapse because of several unforeseen reasons like faulty constructions, design errors, overloading, soil liquefaction, gas explosion, material degradation, terrorist attacks and economic factors also contributing to the collapse. It is also uneconomical to design the structure for unforeseen events unless they have a reasonable chance of occurrence. In order to ensure safety and prevent collapse, many guidelines have been framed by local bodies and government authorities in many countries like the United States Department of Defence (DOD), United States General Service Administration (GSA) and Euro-Codes in European Nations. Some other practices are followed to incorporate redundancies in the structure like detailing, ductile designs, tying of elements at particular locations, and provision of hinges and interconnections. It is also to be admitted that a full-proof safe design structure for accidental events cannot be prepared and implemented as it is uneconomical and the chances of such occurrences are less. This paper reviews past case studies of the collapse of structures with the aim of developing an understanding of the collapse mechanism. This study will definitely help to bring about a detailed improvement in the design to maximise the quality of the construction at a minimal cost.Keywords: unforeseen factors, progressive collapse, collapse resisting mechanisms, column removal scenario
Procedia PDF Downloads 13717 Autoimmune Diseases Associated with Primary Biliary Cirrhosis: A Retrospective Study of 51 Patients
Authors: Soumaya Mrabet, Imen Akkari, Amira Atig, Elhem Ben Jazia
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Introduction: Primary biliary cirrhosis (PBC) is a cholestatic cholangitis of unknown etiology. It is frequently associated with autoimmune diseases, which explains their systematic screening. The aim of our study was to determine the prevalence and the type of autoimmune disorders associated with PBC and to assess their impact on the prognosis of the disease. Material and methods: It is a retrospective study over a period of 16 years (2000-2015) including all patients followed for PBC. In all these patients we have systematically researched: dysthyroidism (thyroid balance, antithyroid autoantibodies), type 1 diabetes, dry syndrome (ophthalmologic examination, Schirmer test and lip biopsy in case of Presence of suggestive clinical signs), celiac disease(celiac disease serology and duodenal biopsies) and dermatological involvement (clinical examination). Results: Fifty-one patients (50 women and one men) followed for PBC were collected. The Mean age was 54 years (37-77 years). Among these patients, 30 patients(58.8%) had at least one autoimmune disease associated with PBC. The discovery of these autoimmune diseases preceded the diagnosis of PBC in 8 cases (26.6%) and was concomitant, through systematic screening, in the remaining cases. Autoimmune hepatitis was found in 12 patients (40%), defining thus an overlap syndrome. Other diseases were Hashimoto's thyroiditis (n = 10), dry syndrome (n = 7), Gougerot Sjogren syndrome (n=6), celiac disease (n = 3), insulin-dependent diabetes (n = 1), scleroderma (n = 1), rheumatoid arthritis (n = 1), Biermer Anemia (n=1) and Systemic erythematosus lupus (n=1). The two groups of patients with PBC with or without associated autoimmune disorders were comparable for bilirubin levels, Child-Pugh score, and response to treatment. Conclusion: In our series, the prevalence of autoimmune diseases in PBC was 58.8%. These diseases were dominated by autoimmune hepatitis and Hashimoto's thyroiditis. Even if their association does not seem to alter the prognosis, screening should be systematic in order to institute an early and adequate management.Keywords: autoimmune diseases, autoimmune hepatitis, primary biliary cirrhosis, prognosis
Procedia PDF Downloads 27616 Electrochemotherapy of Portal Vein Tumor Thrombus as Dowstaging to Liver Transplantation
Authors: Luciano Tarantino, Emanuele Balzano, Paolo Tarantino, Riccardo Aurelio Nasto, Aurelio Nasto
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Liver transplantation (OLT) is contraindicate in Portal Vein tumor Thrombosis (PVTT) from Hepatocellular Carcinoma at hepatic hilum(pH-HCC) Surgery,Thermal ablation and chemotherapy show poorer outcomes Electrochemotherapy (ECT) has been successfully used in patients with pH-HCC with PVTT. We report the results of ECT as downstaging aimed to definitive cure by OLT. F.P. 53 years HBV related Cirrhosis Child-Pugh B7 class; EGDS F2 aesophageal Varices. Diabetes. April 2016 : Enhanced Computed Tomography (CT) detected HCC(n.3 nodules in VII-VIII-VI;diameter range=25 cm) and PVTT of right portal vein. The patient was considered ineligible for OLT. May 2016: first ablation session with percutaneous Radiofrequency-ablation(RFA) of 3 HCC-nodules . August 2016: second ablation session with ECT of PVTT. CT october 2016: disappearance of PVTT and patent right portal vein. No intraparenchymal recurrence. CT march 2017: No recurrence in portal vein and in the left lobe. local recurrence in the VII-VIII segments. May 2017 : transarterial chemoembolization (TACE) of right lobe recurrences. CT October 2017: patent right portal vein. No recurrence. The patient was reconsidered for OLT. He underwent OLT in April 2018. At 36-months follow-up , no intrahepatic recurrence of HCC occurred. March 2021: enhanced CT and PET/CT detected a single small nodule (1.5 cm) uptaking tracer in the left upper pulmonary lobe, no hepatic recurrence . CT-guided FNB showed metastasis from HCC . June 2021: left lung upper lobectomy . At the current time the patient is alive and recurrence-free at 64 months follow-up. ECT Could be aneffective technique as pre-OLT dowstaging in HCC with PVTT.Keywords: liver tumor ablation, interventional ultrasound, electrochemotherapy, liver transplantation
Procedia PDF Downloads 11915 Enhancement of Light Extraction of Luminescent Coating by Nanostructuring
Authors: Aubry Martin, Nehed Amara, Jeff Nyalosaso, Audrey Potdevin, FrançOis ReVeret, Michel Langlet, Genevieve Chadeyron
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Energy-saving lighting devices based on LightEmitting Diodes (LEDs) combine a semiconductor chip emitting in the ultraviolet or blue wavelength region to one or more phosphor(s) deposited in the form of coatings. The most common ones combine a blue LED with the yellow phosphor Y₃Al₅O₁₂:Ce³⁺ (YAG:Ce) and a red phosphor. Even if these devices are characterized by satisfying photometric parameters (Color Rendering Index, Color Temperature) and good luminous efficiencies, further improvements can be carried out to enhance light extraction efficiency (increase in phosphor forward emission). One of the possible strategies is to pattern the phosphor coatings. Here, we have worked on different ways to nanostructure the coating surface. On the one hand, we used the colloidal lithography combined with the Langmuir-Blodgett technique to directly pattern the surface of YAG:Tb³⁺ sol-gel derived coatings, YAG:Tb³⁺ being used as phosphor model. On the other hand, we achieved composite architectures combining YAG:Ce coatings and ZnO nanowires. Structural, morphological and optical properties of both systems have been studied and compared to flat YAG coatings. In both cases, nanostructuring brought a significative enhancement of photoluminescence properties under UV or blue radiations. In particular, angle-resolved photoluminescence measurements have shown that nanostructuring modifies photons path within the coatings, with a better extraction of the guided modes. These two strategies have the advantage of being versatile and applicable to any phosphor synthesizable by sol-gel technique. They then appear as promising ways to enhancement luminescence efficiencies of both phosphor coatings and the optical devices into which they are incorporated, such as LED-based lighting or safety devices.Keywords: phosphor coatings, nanostructuring, light extraction, ZnO nanowires, colloidal lithography, LED devices
Procedia PDF Downloads 17614 Food Bolus Obstruction: A Rural Hospital’s Experience
Authors: Davina Von Hagt, Genevieve Gibbons, Matt Henderson, Tom Bowles
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Purpose: Food bolus obstructions are common emergency surgical presentations, but there is no established management guideline in a rural setting. Intervention usually involves endoscopic removal after initial medical management has failed. Within a rural setting, this falls upon the general surgeon. There are varied endoscopic techniques that may be used. Methodology: A review of the past fifty cases of food bolus obstruction managed at Albany Health Campus was retrospectively reviewed to assess endoscopic findings and techniques. Operation notes, histopathology, imaging, and patient notes were reviewed. Results: 50 patients underwent gastroscopy for food bolus obstruction from August 2017 to March 2021. Ages ranged from 11 months to 95 years, with the majority of patients aged between 30-70 years. 88% of patients were male. Meat was the most common bolus (20% unspecified, 20% steak, 10% chicken, 6% lamb, 4% sausage, 2% pork). At endoscopy, 12% were found not to have a food bolus obstruction. Two patients were found to have oesophageal cancer, and four patients had a stricture and required dilatation. A variety of methods were used to relieve oesophageal obstruction ranging from pushing through to stomach (24 patients), using an overtube (10 patients), raptor (13 patients), and less common instruments such as Roth net, basket, guidewire, and pronged grasper. One patient had an unsuccessful endoscopic retrieval and required theatre for laparoscopic assisted removal with rendezvous endoscopic piecemeal removal via oesophagus and gastrostomy. Conclusion: Food bolus obstruction is a common emergency presentation. Within the rural setting, management requires innovation and teamwork within the safety of the local experience.Keywords: food bolus obstruction, regional hospital, surgical management, innovative surgical treatment
Procedia PDF Downloads 27213 Liver Transplantation after Downstaging with Electrochemotherapy of Large Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis: A Case Report
Authors: Luciano Tarantino, Emanuele Balzano, Aurelio Nasto
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S.R. 53 years. January 2009: HCV-related cirrhosis, Child-Pugh A5 class, EGDS no aesophageal Varices. No important comorbidities. Treated with PEG-IFN+Ribavirin (march-november 2009) with subsequent sustained virologic response. HCVRNA absent overtime. October 2016 :CT detected small HCC nodule in the VIII segment (diam.=12 mm). Treated with US guided RF-ablation. November 2016 CT: complete necrosis. Unfortunately, the patient dropped out US and CT follow-up controls.September 2018: asthenia and weight loss. CT showed a large tumor infiltrating V-VII-VI segments and complete PVTT of right portal vein and its branches . Surgical Consultation excluded indication to Liver resection and OLT . 23 october 2018: ECT of a large peri-hilar area of the tumor including the PVTT. 1 and 3 months post-treatment CT showed complete necrosis and retraction of the thrombus and residual viable tumor in the peripheral portion of the right lobe . Therefor, the patient was reevaluated for OLT and considered eligible in waiting list . March 2019: CT showed no perihilar or portal vein recurrence and distant progression in the right lobe . March 2019 : Trans-arterial-Radio-therapy (TARE) of the right lobe. Post-treatment CT demonstrated no perihilar or portal vein recurrence and extensive necrosis of the residual tumor . December 2019: CT demonstrated several recurrences of HCC infiltrating the VI and VII segment . Howewer no recurrence was observed at hepatic hilum and in portal vessels . Therefore, on February 2020 the patient received OLT. At 44 months follow-up, no complication or recurrence or liver disfunction have been observed.Keywords: hepatocellular carcinoma, portal vein tumor thrombosis, interventional ultrasound, liver tumor ablation, liver transplantation
Procedia PDF Downloads 6812 Strengths and Challenges to Embrace Attention Deficit/Hyperactivity Disorder (ADHD) in Employment: A Systematic Review
Authors: Adèle Hotte-Meunier, Lisa Sarraf, Alan Bougeard, Félicia Bernier, Chloé Voyer, Jiaxuan Deng, Stéphanie El Asmar, Alina Stamate, Marc Corbière, Patrizia Villotti, Geneviève Sauvé
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Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with psychosocial, educational and occupational functioning. Although often conceptualized as a developmental disorder of childhood, 65% of children with ADHD continue to meet full or partial diagnostic criteria for ADHD in adulthood and an estimated 4% of the workforce has a diagnosis of ADHD. Methods: A systematic review was conducted to understand the experiences of people living with ADHD in the workplace. Articles reporting employment outcomes for people living with were identified by a search in eight databases on four separate occasions from June 27, 2022, to June 21, 2023. A risk of bias assessment for each study was performed using the Mixed Methods Appraisal Tool (MMAT). Results: A total of 79 studies were included in this systematic review (nADHD: 68, 216). Results were synthesized into three broad overarching categories: challenges, strengths and adaptations at work. Further, nine themes were included: ADHD symptoms at work, workplace performance, job satisfaction, interpersonal relationships at work, maladaptive work thoughts and behaviors, personal strengths, embracing ADHD, person-environment fit and accommodations and support. Sex differences were highlighted as a tenth subtheme. ADHD confers both strengths and limitations related to employment. Discussion: Workers with ADHD can not only adapt but thrive in employment with the right person-environment fit, accommodations and support. Many challenges related to ADHD can be managed or remodeled as assets in a workplace environment that fosters acceptance, flexible working practices and openness to neurodiversity.Keywords: neurodivergence, occupation, workplace, person-environment fit
Procedia PDF Downloads 11011 Breech Versus Cephalic Elective Caesarean Deliveries – A Comparison of Immediate Neonatal Outcomes
Authors: Genevieve R. Kan, Jolyon Ford
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Background: Caesarean section has become the routine route of delivery for breech fetuses, but breech cesarean deliveries are hypothesized to have poorer immediate neonatal outcomes when compared to cephalic deliveries. In accordance with this, in many Australian hospitals, the pediatric team is routinely required to attend every elective breech cesarean section in case urgent resuscitation is required. Our study aimed to determine whether term elective breech deliveries indeed had worse immediate neonatal outcomes at delivery, which will justify the necessity of pediatric staff presence at every elective breech cesarean delivery and influence the workload for the pediatric team. Objective: Elective breech cesarean deliveries were compared to elective cephalic cesarean deliveries at 37 weeks gestation or above to evaluate the immediate neonatal outcomes (Apgar scores <7 at 5 minutes, and Special Care Nursery admissions on Day 1 of life) of each group. Design: A retrospective cohort study Method: This study examined 2035 elective breech and cephalic singleton cesarean deliveries at term over 5 years from July 2017 to July 2022 at Frankston Hospital, a metropolitan hospital in Melbourne, Australia. There were 260 breech deliveries and 1775 cephalic deliveries. De-identified patient data were collected retrospectively from the hospital’s electronically integrated pregnancy and birth records to assess demographics and neonatal outcomes. Results: Apgar scores <7 at 5 minutes of life were worse in the breech group compared to the cephalic group (3.4% vs 1.6%). Special Care Nursery admissions on Day 1 of life were also higher for the breech cohort compared to the cephalic cohort (9.6% vs 8.7%). Conclusions: Our results support the expected findings that breech deliveries are associated with worse immediate neonatal outcomes. It, therefore, suggests that routine attendance at elective breech cesarean deliveries by the pediatric team is indeed required to assist with potentially higher needs for neonatal resuscitation and special care nursery admission.Keywords: breech, cesarean section, Apgar scores, special care nursery admission
Procedia PDF Downloads 10610 Effect of Heavy Metals on the Life History Trait of Heterocephalobellus sp. and Cephalobus sp. (Nematode: Cephalobidae) Collected from a Small-Scale Mining Site, Davao de Oro, Philippines
Authors: Alissa Jane S. Mondejar, Florifern C. Paglinawan, Nanette Hope N. Sumaya, Joey Genevieve T. Martinez, Mylah Villacorte-Tabelin
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Mining is associated with increased heavy metals in the environment, and heavy metal contamination disrupts the activities of soil fauna, such as nematodes, causing changes in the function of the soil ecosystem. Previous studies found that nematode community composition and diversity indices were strongly affected by heavy metals (e.g., Pb, Cu, and Zn). In this study, the influence of heavy metals on nematode survivability and reproduction were investigated. Life history analysis of the free-living nematodes, Heterocephalobellus sp. and Cephalobus sp. (Rhabditida: Cephalobidae) were assessed using the hanging drop technique, a technique often used in life history trait experiments. The nematodes were exposed to different temperatures, i.e.,20°C, 25°C, and 30°C, in different groups (control and heavy metal exposed) and fed with the same bacterial density of 1×109 Escherichia coli cells ml-1 for 30 days. Results showed that increasing temperature and exposure to heavy metals had a significant influence on the survivability and egg production of both species. Heterocephalobellus sp. and Cephalobus sp., when exposed to 20°C survived longer and produced few numbers of eggs but without subsequent hatching. Life history parameters of Heterocephalobellus sp. showed that the value of parameters was higher in the control group under net production rate (R0), fecundity (mx) which is also the same value for the total fertility rate (TFR), generation times (G0, G₁, and Gh) and Population doubling time (PDT). However, a lower rate of natural increase (rm) was observed since generation times were higher. Meanwhile, the life history parameters of Cephalobus sp. showed that the value of net production rate (R0) was higher in the exposed group. Fecundity (mx) which is also the same value for the TFR, G0, G1, Gh, and PDT, were higher in the control group. However, a lower rate of natural increase (rm) was observed since generation times were higher. In conclusion, temperature and exposure to heavy metals had a negative influence on the life history of the nematodes, however, further experiments should be considered.Keywords: artisanal and small-scale gold mining (ASGM), hanging drop method, heavy metals, life history trait.
Procedia PDF Downloads 989 New Knowledge Co-Creation in Mobile Learning: A Classroom Action Research with Multiple Case Studies Using Mobile Instant Messaging
Authors: Genevieve Lim, Arthur Shelley, Dongcheol Heo
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Abstract—Mobile technologies can enhance the learning process as it enables social engagement around concepts beyond the classroom and the curriculum. Early results in this ongoing research is showing that when learning interventions are designed specifically to generate new insights, mobile devices support regulated learning and encourage learners to collaborate, socialize and co-create new knowledge. As students navigate across the space and time boundaries, the fundamental social nature of learning transforms into mobile computer supported collaborative learning (mCSCL). The metacognitive interaction in mCSCL via mobile applications reflects the regulation of learning among the students. These metacognitive experiences whether self-, co- or shared-regulated are significant to the learning outcomes. Despite some insightful empirical studies, there has not yet been significant research that investigates the actual practice and processes of the new knowledge co-creation. This leads to question as to whether mobile learning provides a new channel to leverage learning? Alternatively, does mobile interaction create new types of learning experiences and how do these experiences co-create new knowledge. The purpose of this research is to explore these questions and seek evidence to support one or the other. This paper addresses these questions from the students’ perspective to understand how students interact when constructing knowledge in mCSCL and how students’ self-regulated learning (SRL) strategies support the co-creation of new knowledge in mCSCL. A pilot study has been conducted among international undergraduates to understand students’ perspective of mobile learning and concurrently develops a definition in an appropriate context. Using classroom action research (CAR) with multiple case studies, this study is being carried out in a private university in Thailand to narrow the research gaps in mCSCL and SRL. The findings will allow teachers to see the importance of social interaction for meaningful student engagement and envisage learning outcomes from a knowledge management perspective and what role mobile devices can play in these. The findings will signify important indicators for academics to rethink what is to be learned and how it should be learned. Ultimately, the study will bring new light into the co-creation of new knowledge in a social interactive learning environment and challenges teachers to embrace the 21st century of learning with mobile technologies to deepen and extend learning opportunities.Keywords: mobile computer supported collaborative learning, mobile instant messaging, mobile learning, new knowledge co-creation, self-regulated learning
Procedia PDF Downloads 2328 Into the Dreamweaver’s World of the Mandaya and the Tboli: From Folklore to the Woven Fabric
Authors: Genevieve Jorolan Quintero
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In Mindanao, the southern island of the Philippines, two provinces, Davao Oriental and Tboli of South Cotabato, respectively, are homes to indigenous communities known for their dream weavers. Davao Oriental is home to the Mandaya, while Lake Sebu is home to the Tboli. The dream weavers are mostly women who have continued the tradition of weaving, a spiritual practice of handicraft embodying the beliefs of the community. It is believed that a weaver is guided by the Tagamaling, or the nature spirit in Mandaya mythology, and Fu Dalu, or the spirit of the abaca among the Tboli. In the dream, the Tagamaling or Fu Dalu reveals to the weaver the design or the pattern of the dagmay as the abaca woven cloth is called among the Mandaya and the tnalak among the Tboli. The weaver then undertakes the production of this nature-spirit-inspired fabric based on her memory of the dream. This interaction between the spirit world and the human world inspired the theme of the short story with the title Loom of Dreams, published in 2015 by Kritika Kultura, an international peer-reviewed journal of language and literary/cultural studies of the Ateneo de Manila University in the Philippines. In Lake Sebu, a collection of the legendary tnalak with various designs is preserved by the cultural advocate and tnalak collector Reden S. Ulo. About a hundred tnalak designs are housed in a mini museum. The paper discusses how the dagmay and the tnalak of the two Philippine indigenous communities, the Mandaya and the Tboli, embody their folklore and cultural heritage. The specific objectives are: 1. To describe the role of the dreamweavers among the Mandaya and Tboli communities in the Philippines; 2. To analyse how folklore influences the designs on the woven fabric, the dagmay, and the tnalak, and 3. To discuss how dream-weaving helps preserve culture legacy. Ethnography was used in the conduct of this research. Specifically, the following data collection methods were done: 1. a series of visits to the Mandaya and Tboli communities; 2. face-to-face interviews with the respondents from the communities, and 3. the recording of the interviews with the knowledge-bearers and material culture keepers from both communities, the narratives of which were used as a basis for the data analysis. The influence of folklore in the culture and the arts of the indigenous communities is significantly evident in the designs of the dagmay and the tnalak. As the dream weavers continue to weave the dagmay and the tnalak, this cultural legacy will continue to prosper and be preserved for posterity.Keywords: dreamweaver's, Mandaya, mindanao, Philippine folklore, Tboli
Procedia PDF Downloads 1017 Imputation of Incomplete Large-Scale Monitoring Count Data via Penalized Estimation
Authors: Mohamed Dakki, Genevieve Robin, Marie Suet, Abdeljebbar Qninba, Mohamed A. El Agbani, Asmâa Ouassou, Rhimou El Hamoumi, Hichem Azafzaf, Sami Rebah, Claudia Feltrup-Azafzaf, Nafouel Hamouda, Wed a.L. Ibrahim, Hosni H. Asran, Amr A. Elhady, Haitham Ibrahim, Khaled Etayeb, Essam Bouras, Almokhtar Saied, Ashrof Glidan, Bakar M. Habib, Mohamed S. Sayoud, Nadjiba Bendjedda, Laura Dami, Clemence Deschamps, Elie Gaget, Jean-Yves Mondain-Monval, Pierre Defos Du Rau
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In biodiversity monitoring, large datasets are becoming more and more widely available and are increasingly used globally to estimate species trends and con- servation status. These large-scale datasets challenge existing statistical analysis methods, many of which are not adapted to their size, incompleteness and heterogeneity. The development of scalable methods to impute missing data in incomplete large-scale monitoring datasets is crucial to balance sampling in time or space and thus better inform conservation policies. We developed a new method based on penalized Poisson models to impute and analyse incomplete monitoring data in a large-scale framework. The method al- lows parameterization of (a) space and time factors, (b) the main effects of predic- tor covariates, as well as (c) space–time interactions. It also benefits from robust statistical and computational capability in large-scale settings. The method was tested extensively on both simulated and real-life waterbird data, with the findings revealing that it outperforms six existing methods in terms of missing data imputation errors. Applying the method to 16 waterbird species, we estimated their long-term trends for the first time at the entire North African scale, a region where monitoring data suffer from many gaps in space and time series. This new approach opens promising perspectives to increase the accuracy of species-abundance trend estimations. We made it freely available in the r package ‘lori’ (https://CRAN.R-project.org/package=lori) and recommend its use for large- scale count data, particularly in citizen science monitoring programmes.Keywords: biodiversity monitoring, high-dimensional statistics, incomplete count data, missing data imputation, waterbird trends in North-Africa
Procedia PDF Downloads 1586 Fashion Utopias: The Role of Fashion Exhibitions and Fashion Archives to Defining (and Stimulating) Possible Future Fashion Landscapes
Authors: Vittorio Linfante
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Utopìa is a term that, since its first appearance in 1516, in Tommaso Moro’s work, has taken on different meanings and forms in various fields: social studies, politics, art, creativity, and design. The utopias, although of short duration and in their apparent impossibility, have been able to give a shape to the future, laying the foundations for our present and the future of the next generations. The Twentieth century was the historical period crossed by many changes, and it saw the most significant number of utopias not only social, political, and scientific but also artistic, architectural, in design, communication, and, last but not least, in fashion. Over the years, fashion has been able to interpret various utopistic impulses giving form to the most futuristic visions. From the Manifesto del Vestito by Giacomo Balla, through the functional experiments that led to the Tuta by Thayath and the Varst by Aleksandr Rodčenko and Varvara Stepanova, through the Space Age visions of Rudi Gernreich, Paco Rabanne and Pierre Cardin, and the Archizoom’s political actions and their fashion project Vestirsi è facile. Experiments that have continued to the present days through the (sometimes) excessive visions of Hussein Chalayan, Alexander McQueen, and Gareth Pugh or those that are more anchored to the market (but no fewer innovative and visionaries) by Prada, Chanel, and Raf Simmons. If, as Bauman states, it is true that we have entered in a phase of Retrotopia characterized by the inability to think about new forms of the future; it is necessary, more than ever, to redefine the role of history, of its narration and its mise en scène, within the contemporary creative process. A process that increasingly requires an in-depth knowledge of the past for the definition of a renewed discourse about design processes. A discourse in which words like archive, exhibition, curating, revival, vintage, and costume take on new meanings. The paper aims to investigate–through case studies, research, and professional projects–the renewed role of curating and preserving fashion artefacts. A renewed role that–in an era of Retrotopia–museums, exhibitions, and archives can (and must) assume, to contribute to the definition of new design paradigms, capable of overcoming the traditional categories of revival or costume in favour of a more contemporary “mash-up” approach. Mash-up in which past and present, craftsmanship and new technologies, revival and experimentation merge seamlessly. In this perspective, dresses (as well as fashion accessories) should be considered not only as finished products but as artefacts capable of talking about the past and of producing unpublished new stories at the same time. Archives, exhibitions (academic and not), and museums thus become powerful sources of inspiration for fashion: places and projects capable of generating innovation, becoming active protagonists of the contemporary fashion design processes.Keywords: heritage, history, costume and fashion interface, performance, language, design research
Procedia PDF Downloads 1155 Medical and Dietary Potentials of Mare's Milk in Liver Diseases
Authors: Bakytzhan Bimbetov, Abay Zhangabilov, Saule Aitbaeva, Galymzhan Meirambekov
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Mare’s milk (saumal) contains in total about 40 biological components necessary for the human body. The most significant among them are amino acids, fats, carbohydrates, enzymes (lysozyme, amylase), more minerals and vitamins which are well balanced with each other. In Kazakhstan, Company "Eurasia Invest Ltd.” produces a freeze-dried saumal in form of powder by the use of modern German innovative technology by means of evaporating at low temperature (-35°C) with an appropriate pasteurization. Research of freeze-dried biomilk for the qualitative content showed that main ingredients of freshly drown milk are being preserved. We are currently studying medical and dietary properties of freeze-dried mare's milk for diseases of the digestive system, including for nonalcoholic steatohepatitis (NASH) and liver cirrhosis (LC) viral etiology. The studied group consisted of 14 patients with NASH, and 7 patients with LC viral etiology of Class A severity degree as per Child-Pugh. Patients took freeze-dried saumal, preliminary dissolved in boiled warm water (24 g. powder per 200 ml water) 3-4 times a day for a month in conjunction with basic therapy. The results were compared to a control group (11 patients with NASH and LC) who received only basic therapy without mare’s milk. Results of preliminary research showed an improvement of subjective and objective conditions of all patients, but more significant improvement of clinical symptoms and syndromes were observed in the treatment group compared to the control one. Patients with NASH significantly over time compared to the beginning of therapy decreased asthenic and dyspeptic syndromes (p<0,01). Hepatomegaly, identified on the basis of ultrasound prior to treatment was observed in 92,8±2,4% of patients, and after combination therapy hepatomegaly the rate decreased by 14,3%, amounting to 78,5±2,8%. Patients with LC also noted the improvement of asthenic (p<0,01) and dyspeptic (p<0,05) syndromes and hemorrhagic syndrome (nosebleeds and bleeding gums when brushing your teeth, p<0,05), and jaundice. Laboratory study also showed improvement in the research group, but more significant changes were observed in the experimental group. Group of patients with NASH showed a significant improvement of index in cytolysis in conjunction with a combination therapy (p<0,05). In the control group, these indicators were also improved, but they were not statistically reliable (p>0,05). Markers of liver failure were additionally studied during the study of laboratory parameters in patients with liver cirrhosis, in particular, bilirubin, albumin and prothrombin index (PTI). Combined therapy with the use of basic treatment and mare's milk showed a significant improvement in cytolysis and bilirubin (p<0,05). In our opinion, a very important and interesting fact is that, in conjunction with basic therapy, the use of mare's milk revealed an improvement of liver function in the form of normalized PTI and albumin in patients with liver cirrhosis viral etiology. Results of this work have shown therapeutic efficiency of the use of mare's milk in complex treatment of patients with liver disease and require further in-depth study.Keywords: liver cirrhosis, non-alcohol steatohepatitis, saumal, mare’s milk
Procedia PDF Downloads 2294 Pharmacokinetics and Safety of Pacritinib in Patients with Hepatic Impairment and Healthy Volunteers
Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean
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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics
Procedia PDF Downloads 299