Search results for: dual antiplatelet therapy (DAPT)
1640 Reliable Soup: Reliable-Driven Model Weight Fusion on Ultrasound Imaging Classification
Authors: Shuge Lei, Haonan Hu, Dasheng Sun, Huabin Zhang, Kehong Yuan, Jian Dai, Yan Tong
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It remains challenging to measure reliability from classification results from different machine learning models. This paper proposes a reliable soup optimization algorithm based on the model weight fusion algorithm Model Soup, aiming to improve reliability by using dual-channel reliability as the objective function to fuse a series of weights in the breast ultrasound classification models. Experimental results on breast ultrasound clinical datasets demonstrate that reliable soup significantly enhances the reliability of breast ultrasound image classification tasks. The effectiveness of the proposed approach was verified via multicenter trials. The results from five centers indicate that the reliability optimization algorithm can enhance the reliability of the breast ultrasound image classification model and exhibit low multicenter correlation.Keywords: breast ultrasound image classification, feature attribution, reliability assessment, reliability optimization
Procedia PDF Downloads 851639 Counseling Ethics in Turkish Counseling Programs
Authors: Umut Arslan, John Sommers Flanagan
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The purpose of this study was to investigate qualifications of ethics training in counselor education programs in Turkey. The survey data were collected from 251 Turkish counseling students to examine differences in ethical judgments between freshmen and seniors. Chi-square analysis was used to analyze the data from an ethical practice and belief survey. This survey was used to assess counselor candidates’ ethical judgments regarding Turkish counseling ethical codes and sources of ethics information. Statistically significant differences were found between university seniors and freshmen on items that are related to confidentiality, dual relationships, and professional relationships. Furthermore, patterns based on demographic information showed significant differences as a result of gender, economic status, and parents’ educational level. Participants gave the highest rating of information sources to Turkish counseling ethical codes.Keywords: ethics, training, Turkey, counselor, education
Procedia PDF Downloads 3721638 Probability Fuzzy Aggregation Operators in Vehicle Routing Problem
Authors: Anna Sikharulidze, Gia Sirbiladze
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For the evaluation of unreliability levels of movement on the closed routes in the vehicle routing problem, the fuzzy operators family is constructed. The interactions between routing factors in extreme conditions on the roads are considered. A multi-criteria decision-making model (MCDM) is constructed. Constructed aggregations are based on the Choquet integral and the associated probability class of a fuzzy measure. Propositions on the correctness of the extension are proved. Connections between the operators and the compositions of dual triangular norms are described. The conjugate connections between the constructed operators are shown. Operators reflect interactions among all the combinations of the factors in the fuzzy MCDM process. Several variants of constructed operators are used in the decision-making problem regarding the assessment of unreliability and possibility levels of movement on closed routes.Keywords: vehicle routing problem, associated probabilities of a fuzzy measure, choquet integral, fuzzy aggregation operator
Procedia PDF Downloads 3261637 Performance Analysis of Heterogeneous Cellular Networks with Multiple Connectivity
Authors: Sungkyung Kim, Jee-Hyeon Na, Dong-Seung Kwon
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Future mobile networks following 5th generation will be characterized by one thousand times higher gains in capacity; connections for at least one hundred billion devices; user experience capable of extremely low latency and response times. To be close to the capacity requirements and higher reliability, advanced technologies have been studied, such as multiple connectivity, small cell enhancement, heterogeneous networking, and advanced interference and mobility management. This paper is focused on the multiple connectivity in heterogeneous cellular networks. We investigate the performance of coverage and user throughput in several deployment scenarios. Using the stochastic geometry approach, the SINR distributions and the coverage probabilities are derived in case of dual connection. Also, to compare the user throughput enhancement among the deployment scenarios, we calculate the spectral efficiency and discuss our results.Keywords: heterogeneous networks, multiple connectivity, small cell enhancement, stochastic geometry
Procedia PDF Downloads 3311636 Spectrophotometric Methods for Simultaneous Determination of Binary Mixture of Amlodipine Besylate and Atenolol Based on Dual Wavelength
Authors: Nesrine T. Lamie
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Four, accurate, precise, and sensitive spectrophotometric methods are developed for the simultaneous determination of a binary mixture containing amlodipine besylate (AM) and atenolol (AT) where AM is determined at its λmax 360 nm (0D), while atenolol can be determined by different methods. Method (A) is absorpotion factor (AFM). Method (B) is the new Ratio Difference method(RD) which measures the difference in amplitudes between 210 and 226 nm of ratio spectrum., Method (C) is novel constant center spectrophotometric method (CC) Method (D) is mean centering of the ratio spectra (MCR) at 284 nm. The calibration curve is linear over the concentration range of 10–80 and 4–40 μg/ml for AM and AT, respectively. These methods are tested by analyzing synthetic mixtures of the cited drugs and they are applied to their commercial pharmaceutical preparation. The validity of results was assessed by applying standard addition technique. The results obtained were found to agree statistically with those obtained by a reported method, showing no significant difference with respect to accuracy and precision.Keywords: amlodipine, atenolol, absorption factor, constant center, mean centering, ratio difference
Procedia PDF Downloads 3041635 Mycophenolate-Induced Disseminated TB in a PPD-Negative Patient
Authors: Megan L. Srinivas
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Individuals with underlying rheumatologic diseases such as dermatomyositis may not adequately respond to tuberculin (PPD) skin tests, creating false negative results. These illnesses are frequently treated with immunosuppressive therapy making proper identification of TB infection imperative. A 59-year-old Filipino man was diagnosed with dermatomyositis on the basis of rash, electromyography, and muscle biopsy. He was initially treated with IVIG infusions and transitioned to oral prednisone and mycophenolate. The patient’s symptoms improved on this regimen. Six months after starting mycophenolate, the patient began having fevers, night sweats, and productive cough without hemoptysis. He moved from the Philippines 5 years prior to dermatomyositis diagnosis, denied sick contacts, and was PPD negative both at immigration and immediately prior to starting mycophenolate treatment. A third PPD was negative following the onset of these new symptoms. He was treated for community-acquired pneumonia, but symptoms worsened over 10 days and he developed watery diarrhea and a growing non-tender, non-mobile mass on the left side of his neck. A chest x-ray demonstrated a cavitary lesion in right upper lobe suspicious for TB that had not been present one month earlier. Chest CT corroborated this finding also exhibiting necrotic hilar and paratracheal lymphadenopathy. Neck CT demonstrated the left-sided mass as cervical chain lymphadenopathy. Expectorated sputum and stool samples contained acid-fast bacilli (AFB), cultures showing TB bacteria. Fine-needle biopsy of the neck mass (scrofula) also exhibited AFB. An MRI brain showed nodular enhancement suspected to be a tuberculoma. Mycophenolate was discontinued and dermatomyositis treatment was switched to oral prednisone with a 3-day course of IVIG. The patient’s infection showed sensitivity to standard RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) treatment. Within a week of starting RIPE, the patient’s diarrhea subsided, scrofula diminished, and symptoms significantly improved. By the end of treatment week 3, the patient’s sputum no longer contained AFB; he was removed from isolation, and was discharged to continue RIPE at home. He was discharged on oral prednisone, which effectively addressed his dermatomyositis. This case illustrates the unreliability of PPD tests in patients with long-term inflammatory diseases such as dermatomyositis. Other immunosuppressive therapies (adalimumab, etanercept, and infliximab) have been affiliated with conversion of latent TB to disseminated TB. Mycophenolate is another immunosuppressive agent with similar mechanistic properties. Thus, it is imperative that patients with long-term inflammatory diseases and high-risk TB factors initiating immunosuppressive therapy receive a TB blood test (such as a quantiferon gold assay) prior to the initiation of therapy to ensure that latent TB is unmasked before it can evolve into a disseminated form of the disease.Keywords: dermatomyositis, immunosuppressant medications, mycophenolate, disseminated tuberculosis
Procedia PDF Downloads 2061634 MR Imaging Spectrum of Intracranial Infections: An Experience of 100 Cases in a Tertiary Hospital in Northern India
Authors: Avik Banerjee, Kavita Saggar
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Infections of the nervous system and adjacent structures are often life-threatening conditions. Despite the recent advances in neuroimaging evaluation, the diagnosis of unclear infectious CNS disease remains a challenge. Our aim is to evaluate the typical and atypical neuro-imaging features of the various routinely encountered CNS infected patients so as to form guidelines for their imaging recognition and differentiation from tumoral, vascular and other entities that warrant a different line of therapy.Keywords: central nervous system (CNS), Cerebro Spinal Fluid (Csf), Creutzfeldt Jakob Disease (CJD), progressive multifocal leukoencephalopathy (PML)
Procedia PDF Downloads 3011633 Embodied Spirituality in Gestalt Therapy
Authors: Silvia Alaimo
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This lecture brings to our attention the theme of spirituality within Gestalt therapy’s theoretical and clinical perspectives and which is closely connected to the fertile emptiness and creative indifference’ experiences. First of all, the premise that must be done is the overcoming traditional western culture’s philosophical and religious misunderstandings, such as the dicotomy between spirituality and pratical/material daily life, as well as the widespread secular perspective of classic psychology. Even fullness and emptiness have traditionally been associated with the concepts of being and not being. "There is only one way through which we can contact the deepest layers of our existence, rejuvenate our thinking and reach intuition (the harmony of thought and being): inner silence" (Perls) *. Therefore, "fertile void" doesn't mean empty in itself, but rather an useful condition of every creative and responsible act, making room for a deeper dimension close to spirituality. Spirituality concerns questions about the meaning of existence, which lays beyond the concrete and literal dimension, looking for the essence of things, and looking at the value of personal experience. Looking at fundamentals of Gestalt epistemology, phenomenology, aesthetics, and the relationship, we can reach the heart of a therapeutic work that takes spiritual contours and which are based on an embodied (incarnate size), through the relational aesthetic knowledge (Spagnuolo Lobb ), the deep contact with each other, the role of compassion and responsibility, as the patient's recognition criteria (Orange, 2013) rooted in the body. The aesthetic dimension, like the spiritual dimension to which it is often associated, is a subtle dimension: it is the dimension of the essence of things, of their "soul." In clinical practice, it implies that the relationship between therapist and patient is "in the absence of judgment," also called "zero point of creative indifference," expressed by ‘therapeutic mentality’. It consists in following with interest and authentic curiosity where the patient wants to go and support him in his intentionality of contact. It’s a condition of pure and simple awareness, of the full acceptance of "what is," a moment of detachment from one's own life in which one does not take oneself too seriously, a starting point for finding a center of balance and integration that brings to the creative act, to growth, and, as Perls would say, to the excitement and adventure of living.Keywords: spirituality, bodily, embodied aesthetics, phenomenology, relationship
Procedia PDF Downloads 1371632 Binge Eating among Women Who Suffer from Psychological Abuse in Their Relationship: The Moderating Role of Defense Mechanisms
Authors: Orly Yona Drori, Shirley Ben Shlomo
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Objectives: The participants will be able to recognize the predictors of binge eating addiction among women who suffer from psychological abuse in their relationships and will recognize the role of woman's defense mechanisms in moderating the association between psychological abuse and binge eating addiction. Methods: A convenience sample of 380 Israeli women in relationships were located via the Internet, and after consenting to participate in the study, they completed a series of structured questionnaires (The Yale Food Addiction Scale; The Defense Style Questionnaire; psychological maltreatment of women by their male partners; level of differentiation of self; sociodemographic questionnaire). Results: The higher the level of differentiation and mature defense mechanisms, the less addictive a woman is. However, the level of addiction among women who experience psychological abuse within their intimate relations is higher than women who do not experience psychological abuse in their relationship. Among women who experienced psychological abuse in their relations, the defense mechanisms moderate the association between psychological abuse within intimate relations and the extent of the addiction to binge eating. Conclusions: The study contributes to the therapy of women with binge eating addictions, as it raises awareness of therapeutic-related content that could strengthen women and help them to cope with situations in their lives without the need to binge. One of the significant variables for therapeutic work is the level of differentiation of the self. In addition, identifying the types of defense mechanisms might help to match treatment to the woman's emotional needs. The current study found also that it is important to identify the environmental systems by which the addict is surrounded, such as whether woman is in an abusive relationship. Finally the study leads to the recognition that binge eating, which is usually treated with an emphasis on nutritional behavior change, is an addiction, and as such, it requires a combination of mental, nutritional and behavioral therapy. In view of this approach, it is recommended that treating a woman who is addicted to binge eating should involve a multi-disciplinary team comprised of physicians, clinical dietitians, and clinical psychotherapists.Keywords: binge eating, defence mechanism, food addiction, psychological abuse
Procedia PDF Downloads 1691631 Malaysian Knowledge, Belief and Attitude towards Hypnosis as a Health Intervention: An Interpretative Phenomenological Analysis
Authors: Ying Chern Yeoh, Mark J. Forshaw
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Although hypnosis has been widely endorsed in Europe since 1950s, it was still viewed as a typically new therapy in Asia. There are very little findings regarding hypnosis in Asian countries, especially in culturally diverse countries such as Malaysia. The knowledge of the beneficial effects of hypnosis was not widespread to the public, however knowledge of the negative effects was frequently being highlighted. Therefore, the acceptance of hypnosis as a new effective health treatment can be a challenge in Malaysia. Recognising Malaysian’s perception, belief and attitude towards hypnosis could increase the public awareness of hypnosis, which in turn will alter their misconception and increase acceptance of hypnosis as an effective therapy. Eight individuals (N = 8) from the general public with different background, ethnicity (Malays, Chinese and Indians) and religion (Islamic, Buddhism, Hinduism, Taoism, Christianity, free-thinker) and two local experienced practitioners with minimum of five years experiences (N = 2) were being interviewed to determine their views, beliefs and level of acceptance towards hypnosis. Semi-structured interviews were conducted, transcribed with pseudonyms and analyzed by using Interpretative Phenomenological Analysis. The three emergent themes were illustrated under the captions of ‘traditional vs mainstream’, ‘myths vs truth’, and ‘dissemination and public awareness’. The finding suggested that individual knowledge and personal experience primarily influenced people’s level of acceptance towards hypnosis as a beneficial health treatment, rather than the diversity of cultural and religious background. Subsequent findings regarding hypnosis and the effort of promoting it will provide the society an opportunity to increase public education and health awareness. Several associations had started to advance its development by organizing conferences and setting up therapeutic centers. However, health promotion on hypnosis is yet to be conducted to raise public awareness of its beneficial effects. By requesting for hypnosis to be included as a subject in medical education and psychology curriculum and formatting it under Ministry of Health’s legislation body might enhance the knowledge of hypnosis for Malaysian as one of the health intervention in the future.Keywords: awareness, hypnosis, intervention, Malaysian, promotion
Procedia PDF Downloads 1581630 Diffusion of Social Innovation in Thai Community Enterprises
Authors: Thanisa Sirithaporn
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The study aims to examine the diffusion of social innovation among Thai Community Enterprises in conjunction with a singular case study of a medium-sized corporation that has successfully transitioned from a charitable foundation to a sustainable, profitable entity creating value for both shareholders and the communities in which it operates. It seeks to bridge the gap between different streams of aligned research in the fields of diffusion, social innovation, and community enterprises into a more cohesive conceptual framework and thus to better understand the historical and current impediments that have resulted in so many enterprises failing to be sustainable. The methodology is mixed and dual phased. The initial quantitative phase uses a questionnaire as the main research instrument distributed among community enterprises throughout Thailand which will provide the themes for the qualitative phase through semi-structured interviews with key stakeholders at a commercial enterprise actively engaged in social innovation. The findings seek to present a more comprehensive conceptual framework and actionable guidelines to aid community enterprises to develop social innovation in a sustainable manner that creates value to its beneficiaries.Keywords: diffusion, community enterprises, social innovation, Thailand
Procedia PDF Downloads 1331629 Technical Specifications of Bombardier Challenger 605 SN 5769 Aircraft
Authors: Rohan Sarker, Jon P. Conlon
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The Bombardier Challenger 605 SN 5769 is a versatile business jet known for its superior range, advanced avionics, and spacious cabin. Powered by two General Electric CF34-3B engines, each producing 8,729 pounds of thrust, the aircraft offers a maximum range of 4,000 nautical miles, allowing for non-stop transcontinental flights. It operates at a maximum cruising speed of Mach 0.82 (541 mph) and a service ceiling of 41,000 feet, ensuring efficient, high-altitude travel. The aircraft’s avionics suite is equipped with the Rockwell Collins Pro Line 21, offering advanced navigation, communication, and weather systems. The cockpit features dual Flight Management Systems (FMS) and GPS to enhance operational safety and precision. Inside, the Challenger 605 boasts a luxurious and customizable cabin that accommodates up to 12 passengers. The aircraft also provides ample baggage space, excellent short-field performance, and impressive fuel efficiency, making it ideal for business or personal long-range travel.Keywords: aircraft, airframe, Bombardier, engines
Procedia PDF Downloads 281628 Management of Hypoglycemia in Von Gierke’s Disease
Authors: Makda Aamir, Sood Aayushi, Syed Omar, Nihan Khuld, Iskander Peter, Ijaz Naeem, Sharma Nishant
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Introduction:Glycogen Storage Disease Type-1 (GSD-1) is a rare phenomenon primarily affecting the liver and kidney. Excessive accumulation of glycogen and fat in liver, kidney, and intestinal mucosa is noted in patients with deficiency of Glucose-6-phosphatase deficiency. Patients with GSD-1 have a wide spectrum of symptoms, including hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, and growth retardation. Age of onset, rate of disease progression and its severity is variable in this disease.Case:An 18-year-old male with GSD-1a, Von Gierke’s disease, hyperuricemia, and hypertension presented to the hospital with nausea and vomiting. The patient followed an hourly cornstarch regimen during the day and overnight through infusion via a PEG tube. The complaints started at work, where he was unable to tolerate oral cornstarch. He washemodynamically stable on arrival. ABG showed pH 7.372, PaCO2 30.3, and PaO2 92.2. WBC 16.80, K+ 5.8, HCO3 13, BUN 28, Cr 2.2, Glucose 60, AST 115, ALT 128, Cholesterol 352, Triglycerides >1000, Uric Acid 10.6, Lactic Acid 11.8 which trended down to 8.0. CT abdomen showed hepatomegaly and fatty infiltration with the PEG tube in place.He was admitted to the ICU and started on D5NS for hypoglycemia and lactic acidosis. Per request by the patient’s pediatrician, he was transitioned to IV D10/0.45NS at 110mL/Hr to maintain blood glucose above 75 mg/L. Frequent accuchecks were done till he could tolerate his dietary regimen with cornstarch. Lactic acid downtrend to 2.9, and accuchecks ranged between 100-110. Cr improved to 1.3, and his home medications (Allopurinol and Lisinopril) were resumed. He was discharged in stable condition with plans for further genetic therapy work up.Discussion:Mainstay therapy for Von Gierke’s Disease is the prevention of metabolic derangements for which dietary and lifestyle changes are recommended. A low fructose and sucrose diet is recommended by limiting the intake of galactose and lactose to one serving per day. Hypoglycemia treatment in such patients is two-fold, utilizing both quick and stable release sources. Cornstarch has been one such therapy since the 1980s; its slow digestion provides a steady release of glucose over a longer period of time as compared with other sources of carbohydrates. Dosing guidelines vary from age to age and person to person, but it is highly recommended to check BG levels frequently to maintain a BG > 70 mg/dL. Associated high levels of triglycerides and cholesterol can be treated with statins, fibrates, etc. Conclusion:The management of hypoglycemia in GSD 1 disease presents various obstacles which could prove to be fatal. Due to the deficiency of G6P, treatment with a specialized hypoglycemic regimen is warranted. A D10 ½ NS infusion can be used to maintain blood sugar levels as well as correct metabolic or lactate imbalances. Infusion should be gradually weaned off after the patient can tolerate oral feeds as this can help prevent the risk of hypoglycemia and other derangements. Further research is needed in regards to these patients for more sustainable regimens.Keywords: von gierke, glycogen storage disease, hypoglycemia, genetic disease
Procedia PDF Downloads 1071627 A Fully Coupled Thermo-Hydraulic Mechanical Elastoplastic Damage Constitutive Model for Porous Fractured Medium during CO₂ Injection
Authors: Nikolaos Reppas, Yilin Gui
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A dual-porosity finite element-code will be presented for the stability analysis of the wellbore during CO₂ injection. An elastoplastic damage response will be considered to the model. The Finite Element Method (FEM) will be validated using experimental results from literature or from experiments that are planned to be undertaken at Newcastle University. The main target of the research paper is to present a constitutive model that can help industries to safely store CO₂ in geological rock formations and forecast any changes on the surrounding rock of the wellbore. The fully coupled elastoplastic damage Thermo-Hydraulic-Mechanical (THM) model will determine the pressure and temperature of the injected CO₂ as well as the size of the radius of the wellbore that can make the Carbon Capture and Storage (CCS) procedure more efficient.Keywords: carbon capture and storage, Wellbore stability, elastoplastic damage response for rock, constitutive THM model, fully coupled thermo-hydraulic-mechanical model
Procedia PDF Downloads 1721626 Effective, Affordable, and Accessible Treatment for Pregnancy’s Commonest Complication: Online Synchronous Interpersonal Psychotherapy for Mothers with Postpartum Depression
Authors: Vivian Polak, Lena Verdeli, Wendy Lou, Caroline Lovett
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Postnatal depression (PND) is a common complication of childbirth that increases the risk of future depressive episodes in women, postpartum depression in partners, as well as social, emotional, behavioural, language, and cognitive problems in offspring. Although psychotherapy, and in particular Group Interpersonal Psychotherapy (IPT-G), has been proven effective in treating PND, it remains largely inaccessible. However, research has indicated that online synchronous group therapy can be equally as effective as in-person therapy and is a more affordable and accessible modality of treatment. This study aimed to ascertain whether delivering IPT-G virtually when compared to treatment as usual, could more effectively reduce depressive and anxiety symptoms, enhance mother-infant attachment, improve the couple relationship, augment social support, improve overall functioning, and enhance the quality of life for women in rural and northern Ontario who are suffering from PND. By bridging the gap in access to mental health services during the postpartum period, this study seeks to improve the well-being of mothers and their families in rural and northern Ontario, Canada. A randomized controlled trial was conducted to determine whether virtual IPT-G plus treatment as usual would be more effective than treatment as usual alone in treating women with PND in Ontario, Canada. Preliminary results indicate that women who received virtual IPT-G had a clinically and statistically significant decrease in overall depressive symptoms compared to their counterparts who received only the treatment as usual. As such, providing online synchronous IPT-G in the perinatal period not only has the potential to improve women's outcomes in the present but also to decrease future health costs, reduce the burden on the educational and justice systems, and decrease the number of disability life years lost to postnatal depression.Keywords: family wellbeing, group psychotherapy, interpersonal psychotherapy, postnatal depression, virtual psychotherapy
Procedia PDF Downloads 681625 Directivity in the Dramatherapeutic Process for People with Addictive Behaviour
Authors: Jakub Vávra, Milan Valenta, Petr Kosek
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This article presents a perspective on the conduct of the dramatherapy process with persons with addictive behaviours with regard to the directiveness of the process. Although drama therapy as one of the creative arts approaches is rather non-directive in nature, depending on the clientele, there may be a need to structure the process more and, depending on the needs of the clients, to guide the process more directive. The specificity for people with addictive behaviours is discussed through the prism of the dramatherapeutic perspective, where we can find both a psychotherapeutic component as well as a component touching on expression and art, which is rather non-directive in nature. Within the context of practice with clients, this theme has repeatedly emerged and dramatherapists themselves have sought to find ways of coping with clients' demands and needs for structure and guidance within the dramatherapy process. Some of the outcomes from the supervision work also guided the research. Based on this insight, the research questions were approached. The first research question asks: in what ways is directive in dramatherapy manifested and manifested in the process? The second research question then complements the first and asks: to which phenomena are directivity in dramatherapy linked? In relation to the research questions, data were collected using focus groups and field notes. The qualitative approach of Content analysis and Relational analysis was chosen as the methodology. For analyzing qualitative research, we chose an Inductive coding scheme: Open coding, Axial coding, Pattern matching, Member checking, and Creating a coding scheme. In the presented partial research results, we find recurrent schemes related to directive coding in drama therapy. As an important element, directive leadership emerges in connection with safety for the client group, then in connection with the clients' order and also the department of the facility, and last but not least, to the personality of the drama therapist. By careful analysis and looking for patterns in the research results, we can see connections that are impossible to interpret at this stage but already provide clues to our understanding of the topic and open up further avenues for research in this area.Keywords: dramatherapy, directivity, personal approach, aims of dramatherapy process, safetyness
Procedia PDF Downloads 691624 Gas Permeation Behavior of Single and Mixed Gas Components Using an Asymmetric Ceramic Membrane
Authors: Ngozi Claribelle Nwogu, Mohammed Nasir Kajama, Godson Osueke, Edward Gobina
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A unique sol–gel dip-coating process to form an asymmetric silica membrane with improved membrane performance and reproducibility has been reported. First, we deposited repeatedly a silica solution on top of a commercial alumina membrane support to improve its structural make up. The coated membrane is further processed under clean room conditions to avoid dust impurity and subsequent drying in an oven for high thermal, chemical and physical stability. The resulting asymmetric membrane exhibits a gradual change in the membrane layer thickness. Compared to a single-layer process using only the membrane support, the dual-layer process improves both flux and selectivity. For the scientifically significant difficulties of natural gas purification, collective CO2, CH4 and H2 gas fluxes and separation factors obtained gave reasonably excellent values. In addition, the membrane selectively separated hydrogen as demonstrated by a high concentration of hydrogen recovery.Keywords: gas permeation, silica membrane, separation factor, membrane layer thickness
Procedia PDF Downloads 3591623 Blood Flow Estimator of the Left Ventricular Assist Device Based in Look-Up-Table: In vitro Tests
Authors: Tarcisio F. Leao, Bruno Utiyama, Jeison Fonseca, Eduardo Bock, Aron Andrade
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This work presents a blood flow estimator based in Look-Up-Table (LUT) for control of Left Ventricular Assist Device (LVAD). This device has been used as bridge to transplantation or as destination therapy to treat patients with heart failure (HF). Destination Therapy application requires a high performance LVAD; thus, a stable control is important to keep adequate interaction between heart and device. LVAD control provides an adequate cardiac output while sustaining an appropriate flow and pressure blood perfusion, also described as physiologic control. Because thrombus formation and system reliability reduction, sensors are not desirable to measure these variables (flow and pressure blood). To achieve this, control systems have been researched to estimate blood flow. LVAD used in the study is composed by blood centrifugal pump, control, and power supply. This technique used pump and actuator (motor) parameters of LVAD, such as speed and electric current. Estimator relates electromechanical torque (motor or actuator) and hydraulic power (blood pump) via LUT. An in vitro Mock Loop was used to evaluate deviations between blood flow estimated and actual. A solution with glycerin (50%) and water was used to simulate the blood viscosity with hematocrit 45%. Tests were carried out with variation hematocrit: 25%, 45% and 58% of hematocrit, or 40%, 50% and 60% of glycerin in water solution, respectively. Test with bovine blood was carried out (42% hematocrit). Mock Loop is composed: reservoir, tubes, pressure and flow sensors, and fluid (or blood), beyond LVAD. Estimator based in LUT is patented, number BR1020160068363, in Brazil. Mean deviation is 0.23 ± 0.07 L/min for mean flow estimated. Larger mean deviation was 0.5 L/min considering hematocrit variation. This estimator achieved deviation adequate for physiologic control implementation. Future works will evaluate flow estimation performance in control system of LVAD.Keywords: blood pump, flow estimator, left ventricular assist device, look-up-table
Procedia PDF Downloads 1861622 Conceptualizing Psycho-Social Intervention with Juvenile Offenders as Attachment Therapy: A Practical Approach
Authors: Genziana Lay
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A wide majority of older children and adolescents who enter the juvenile court system present with an array of problematic symptoms and behaviors including anxiety, depression, aggressive acting out, detachment, and substance abuse. Attachment theory offers a framework for understanding normative and pathological functioning, which during development is influenced by emotional, social and cognitive elements. There is clear evidence that children and adolescents with the highest risk of developing adaptation problems present an insecure attachment profile. Most offending minors have experienced dysfunctional family relationships as well as social and/or economic deprivation. Their maladaptive attachment develops not only through their relationship with caregivers but with the environment at large. Activation of their faulty attachment system leads them to feel emotionally overwhelmed and engage in destructive behaviors and decision-making. A psycho-social intervention with this population conceptualized as attachment therapy is a multi-faceted, practical approach that has shown excellent results in terms of increased psychological well-being and drastically reduced rates of re-offense/ destructive behavior. Through several; components including psychotherapy, monitoring, volunteering, meditation and socialization, the program focuses on seven dimensions: self-efficacy, responsibility, empathy/reparation, autonomy/security, containment/structure, insight building, and relational health. This paper presents the program and illustrates how the framework of attachment theory practically applied to psycho-social intervention has great therapeutic and social reparation potential. Preliminary evidence drawn from the Sassari Juvenile Court is very promising; this paper will illustrate these results and propose an even more comprehensive, applicable approach to psycho-social reparative intervention that leads to greater psychological health and reduced recidivism in the child and adolescent population.Keywords: attachment, child, adolescent, crime, juvenile, psychosocial
Procedia PDF Downloads 1721621 Targeting Glucocorticoid Receptor Eliminate Dormant Chemoresistant Cancer Stem Cells in Glioblastoma
Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu
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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.
Procedia PDF Downloads 841620 Intrusion Detection Using Dual Artificial Techniques
Authors: Rana I. Abdulghani, Amera I. Melhum
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With the abnormal growth of the usage of computers over networks and under the consideration or agreement of most of the computer security experts who said that the goal of building a secure system is never achieved effectively, all these points led to the design of the intrusion detection systems(IDS). This research adopts a comparison between two techniques for network intrusion detection, The first one used the (Particles Swarm Optimization) that fall within the field (Swarm Intelligence). In this Act, the algorithm Enhanced for the purpose of obtaining the minimum error rate by amending the cluster centers when better fitness function is found through the training stages. Results show that this modification gives more efficient exploration of the original algorithm. The second algorithm used a (Back propagation NN) algorithm. Finally a comparison between the results of two methods used were based on (NSL_KDD) data sets for the construction and evaluation of intrusion detection systems. This research is only interested in clustering the two categories (Normal and Abnormal) for the given connection records. Practices experiments result in intrude detection rate (99.183818%) for EPSO and intrude detection rate (69.446416%) for BP neural network.Keywords: IDS, SI, BP, NSL_KDD, PSO
Procedia PDF Downloads 3821619 Android Graphics System: Study of Dual-Software VSync Synchronization Architecture and Optimization
Authors: Prafulla Kumar Choubey, Krishna Kishor Jha, S. B. Vaisakh Punnekkattu Chirayil
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In Graphics-display subsystem, frame buffers are shared between producer i.e. content rendering and consumer i.e. display. If a common buffer is operated by both producer and consumer simultaneously, their processing rates mismatch can cause tearing effect in displayed content. Therefore, Android OS employs triple buffered system, taking in to account an additional composition stage. Three stages-rendering, composition and display refresh, operate synchronously on three different buffers, which is achieved by using vsync pulses. This synchronization, however, brings in to the pipeline an additional latency of up to 26ms. The present study details about the existing synchronization mechanism of android graphics-display pipeline and discusses a new adaptive architecture which reduces the wait time to 5ms-16ms in all the use-cases. The proposed method uses two adaptive software vsyncs (PLL) for achieving the same result.Keywords: Android graphics system, vertical synchronization, atrace, adaptive system
Procedia PDF Downloads 3141618 Short Term Effects of Mobilization with Movement in a Patient with Fibromyalgia: A Case Report
Authors: S. F. Kanaan, Fatima Al-Kadi, H. Khrais
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Background: Fibromyalgia is a chronic condition that is characterized by chronic pain that limits physical and functional activities. To our best knowledge, there is currently no key physiotherapy approach recommended to reduce pain and improve function. In addition, there are scarce studies that investigated the effect of manual therapy in the management of Fibromyalgia, and no study investigated the efficacy of Mulligan´s mobilization with movement (MWM) in particular. Methods: A 51-year-old female diagnosed with Fibromyalgia for more than a year. The patient was complaining of generalized pain including neck, lower back, shoulders, elbows, hips, and knees. In addition, the patient reported severe limitation in activities and inability to complete her work as a lawyer. The Intervention provided for the patient consisted of 4 sessions (in two weeks) of MWM for neck, lower back, shoulders, elbows, sacroiliac joint, hips, and knees. The Visual Analogue Scale of pain (VAS), Range of Motion (ROM), 10-minute walk test, Roland Morris Low Back Pain and Disability Questionnaire (RMQ), Disability of the Arm, Shoulder and Hand Score (DASH) were collected at the baseline and at the end of treatment. Results: Average improvement of ROM in the neck, lower back, shoulder, elbows, hips, and knees was 45%. VAS scale changed from pre-treatment to post-treatment as the following: neck pain (9 to 0), lower back pain (8 to 1), shoulders pain (8 to 2), elbows pain (7 to 1), and knees pain (9 to 0). The patient demonstrated improvement in all functional scale from pre-intervention to post-intervention: 10-meter walk test (9.8 to 4.5 seconds), RMQ (21 to 11/24), and DASH (88.7% to 40.5%). The patient did not report any side effect of using this approach. Conclusion: Fibromyalgia can cause joint 'faulty position' leading to pain and dysfunction, which can be reversed by using MWM. MWM showed to have clinically significant improvement in ROM, pain, and ability to walk and a clinically significant reduction in disability in only 4 sessions. This work can be expanded in a larger sample.Keywords: mobilization, fibromyalgia, dysfunction, manual therapy
Procedia PDF Downloads 1731617 The Impact of Total Parenteral Nutrition on Pediatric Stem Cell Transplantation and Its Complications
Authors: R. Alramyan, S. Alsalamah, R. Alrashed, R. Alakel, F. Altheyeb, M. Alessa
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Background: Nutritional support with total parenteral nutrition (TPN) is usually commenced with hematopoietic stem cell transplantation (HSCT) patients. However, it has its benefits and risks. Complications related to central venous catheter such as infections, and metabolic disturbances, including abnormal liver function, is usually of concern in such patients. Methods: A retrospective charts review of all pediatric patients who underwent HSCT between the period 2015-2018 in a tertiary hospital in Riyadh, Saudi Arabia. Patients' demographics, types of conditioning, type of nutrition, and patients' outcomes were collected. Statistical analysis was conducted using SPSS version 22. Frequencies and percentages were used to describe categorical variables. Mean, and standard deviation were used for continuous variables. A P value of less than 0.05 was considered as statically significant. Results: a total of 162 HSCTs were identified during the period mentioned. Indication of allogenic transplant included hemoglobinopathy in 50 patients (31%), acute lymphoblastic leukemia in 21 patients (13%). TPN was used in 96 patients (59.30%) for a median of 14 days, nasogastric tube feeding (NGT) in 16 (9.90%) patients for a median of 11 days, and 71 of patients (43.80%) were able to tolerate oral feeding. Out of the 96 patients (59.30%) who were dependent on TPN, 64 patients (66.7%) had severe mucositis in comparison to 17 patients (25.8%) who were either on NGT or tolerated oral intake. (P-value= 0.00). Sinusoidal obstruction syndrome (SOS) was seen in 14 patients (14.6%) who were receiving TPN compared to none in non-TPN patients (P=value 0.001). Moreover, majority of patients who had SOS received myeloablative conditioning therapy for non-malignant disease (hemoglobinopathy). However, there were no statistically significant differences in Graft-vs-Host Disease (both acute and chronic), bacteremia, and patient outcome between both groups. Conclusions: Nutritional support using TPN is used in majority of patients, especially post-myeloablative conditioning associated with severe mucositis. TPN was associated with VOD, especially in hemoglobinopathy patients who received myeloablative therapy. This may emphasize on use of preventative measures such as fluid restriction, use of diuretics, or defibrotide in high-risk patients.Keywords: hematopoeitic stem cell transplant, HSCT, stem cell transplant, sinusoidal obstruction syndrome, total parenteral nutrition
Procedia PDF Downloads 1571616 Machine Learning Based Digitalization of Validated Traditional Cognitive Tests and Their Integration to Multi-User Digital Support System for Alzheimer’s Patients
Authors: Ramazan Bakir, Gizem Kayar
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It is known that Alzheimer and Dementia are the two most common types of Neurodegenerative diseases and their visibility is getting accelerated for the last couple of years. As the population sees older ages all over the world, researchers expect to see the rate of this acceleration much higher. However, unfortunately, there is no known pharmacological cure for both, although some help to reduce the rate of cognitive decline speed. This is why we encounter with non-pharmacological treatment and tracking methods more for the last five years. Many researchers, including well-known associations and hospitals, lean towards using non-pharmacological methods to support cognitive function and improve the patient’s life quality. As the dementia symptoms related to mind, learning, memory, speaking, problem-solving, social abilities and daily activities gradually worsen over the years, many researchers know that cognitive support should start from the very beginning of the symptoms in order to slow down the decline. At this point, life of a patient and caregiver can be improved with some daily activities and applications. These activities include but not limited to basic word puzzles, daily cleaning activities, taking notes. Later, these activities and their results should be observed carefully and it is only possible during patient/caregiver and M.D. in-person meetings in hospitals. These meetings can be quite time-consuming, exhausting and financially ineffective for hospitals, medical doctors, caregivers and especially for patients. On the other hand, digital support systems are showing positive results for all stakeholders of healthcare systems. This can be observed in countries that started Telemedicine systems. The biggest potential of our system is setting the inter-user communication up in the best possible way. In our project, we propose Machine Learning based digitalization of validated traditional cognitive tests (e.g. MOCA, Afazi, left-right hemisphere), their analyses for high-quality follow-up and communication systems for all stakeholders. R. Bakir and G. Kayar are with Gefeasoft, Inc, R&D – Software Development and Health Technologies company. Emails: ramazan, gizem @ gefeasoft.com This platform has a high potential not only for patient tracking but also for making all stakeholders feel safe through all stages. As the registered hospitals assign corresponding medical doctors to the system, these MDs are able to register their own patients and assign special tasks for each patient. With our integrated machine learning support, MDs are able to track the failure and success rates of each patient and also see general averages among similarly progressed patients. In addition, our platform also supports multi-player technology which helps patients play with their caregivers so that they feel much safer at any point they are uncomfortable. By also gamifying the daily household activities, the patients will be able to repeat their social tasks and we will provide non-pharmacological reminiscence therapy (RT – life review therapy). All collected data will be mined by our data scientists and analyzed meaningfully. In addition, we will also add gamification modules for caregivers based on Naomi Feil’s Validation Therapy. Both are behaving positively to the patient and keeping yourself mentally healthy is important for caregivers. We aim to provide a therapy system based on gamification for them, too. When this project accomplishes all the above-written tasks, patients will have the chance to do many tasks at home remotely and MDs will be able to follow them up very effectively. We propose a complete platform and the whole project is both time and cost-effective for supporting all stakeholders.Keywords: alzheimer’s, dementia, cognitive functionality, cognitive tests, serious games, machine learning, artificial intelligence, digitalization, non-pharmacological, data analysis, telemedicine, e-health, health-tech, gamification
Procedia PDF Downloads 1371615 Synthesis and Characterization of Polycaprolactone for the Delivery of Rifampicin
Authors: Evelyn Osehontue Uroro, Richard Bright, Jing Yang Quek, Krasimir Vasilev
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Bacterial infections have been a challenge both in the public and private sectors. The colonization of bacteria often occurs in medical devices such as catheters, heart valves, respirators, and orthopaedic implants. When biomedical devices are inserted into patients, the deposition of macromolecules such as fibrinogen and immunoglobin on their surfaces makes it easier for them to be prone to bacteria colonization leading to the formation of biofilms. The formation of biofilms on medical devices has led to a series of device-related infections which are usually difficult to eradicate and sometimes cause the death of patients. These infections require surgical replacements along with prolonged antibiotic therapy, which would incur additional health costs. It is, therefore, necessary to prevent device-related infections by inhibiting the formation of biofilms using intelligent technology. Antibiotic resistance of bacteria is also a major threat due to overuse. Different antimicrobial agents have been applied to microbial infections. They include conventional antibiotics like rifampicin. The use of conventional antibiotics like rifampicin has raised concerns as some have been found to have hepatic and nephrotoxic effects due to overuse. Hence, there is also a need for proper delivery of these antibiotics. Different techniques have been developed to encapsulate and slowly release antimicrobial agents, thus reducing host cytotoxicity. Examples of delivery systems are solid lipid nanoparticles, hydrogels, micelles, and polymeric nanoparticles. The different ways by which drugs are released from polymeric nanoparticles include diffusion-based release, elution-based release, and chemical/stimuli-responsive release. Polymeric nanoparticles have gained a lot of research interest as they are basically made from biodegradable polymers. An example of such a biodegradable polymer is polycaprolactone (PCL). PCL degrades slowly by hydrolysis but is often sensitive and responsive to stimuli like enzymes to release encapsulants for antimicrobial therapy. This study presents the synthesis of PCL nanoparticles loaded with rifampicin and the on-demand release of rifampicin for treating staphylococcus aureus infections.Keywords: enzyme, Staphylococcus aureus, PCL, rifampicin
Procedia PDF Downloads 1261614 Clinical Cases of Rare Types of 'Maturity Onset Diabetes of the Young' Diabetes
Authors: Alla Ovsyannikova, Oksana Rymar, Elena Shakhtshneider, Mikhail Voevoda
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In Siberia endocrinologists increasingly noted young patients with the course of diabetes mellitus differing from 1 and 2 types. Therefore we did a molecular genetic study for this group of patients to verify the monogenic forms of diabetes mellitus in them and researched the characteristics of this pathology. When confirming the monogenic form of diabetes, we performed a correction therapy for many patients (transfer from insulin to tablets), prevented specific complications, examined relatives and diagnosed their diabetes at the preclinical stage, revealed phenotypic characteristics of the pathology which led to the high significance of this work. Materials and Methods: We observed 5 patients (4 families). We diagnosed MODY (Maturity Onset Diabetes of the Young) during the molecular genetic testing (direct automatic sequencing). All patients had a full clinical examination, blood samples for biochemical research, determination of C-peptide and TSH, antibodies to b-cells, microalbuminuria, abdominal ultrasound, heart and thyroid ultrasound, examination of ophthalmologist. Results: We diagnosed 3 rare types of MODY: two women had MODY8, one man – MODY6 and man and his mother - MODY12. Patients with types 8 and 12 had clinical features. Age of onset hyperglycemia ranged from 26 to 34 years. In a patient with MODY6 fasting hyperglycemia was detected during a routine examination. Clinical symptoms, complications were not diagnosed. The patient observes a diet. In the first patient MODY8 was detected during first pregnancy, she had itchy skin and mostly postprandial hyperglycemia. Upon examination we determined glycated hemoglobin 7.5%, retinopathy, non-proliferative stage, peripheral neuropathy. She uses a basic bolus insulin therapy. The second patient with MODY8 also had clinical manifestations of hyperglycemia (pruritus, thirst), postprandial hyperglycemia and diabetic nephropathy, a stage of microalbuminuria. The patient was diagnosed autoimmune thyroiditis. She used inhibitors of DPP-4. The patient with MODY12 had an aggressive course. In the detection of hyperglycemia he had complaints of visual impairment, intense headaches, leg cramps. The patient had a history of childhood convulsive seizures of non-epileptic genesis, without organic pathology, which themselves were stopped at the age of 12 years. When we diagnosed diabetes a patient was 28 years, he had hypertriglyceridemia, atherosclerotic plaque in the carotid artery, proliferative retinopathy (lacerocoagulation). Diabetes and early myocardial infarction were observed in three cases in family. We prescribe therapy with sulfonylureas and SGLT-2 inhibitors with a positive effect. At the patient's mother diabetes began at a later age (30 years) and a less aggressive course was observed. She also has hypertriglyceridemia and uses oral hypoglycemic drugs. Conclusions: 1) When young patients with hyperglycemia have extrapancreatic pathologies and diabetic complications with a short duration of diabetes we can assume they have one of type of MODY diabetes. 2) In patients with monogenic forms of diabetes mellitus, the clinical manifestations of hyperglycemia in each succeeding generation are revealed at an earlier age. Research had increased our knowledge of the monogenic forms of diabetes. The reported study was supported by RSCF, research project No. 14-15-00496-P.Keywords: diabetes mellitus, MODY diabetes, monogenic forms, young patients
Procedia PDF Downloads 2441613 Enhanced Oxygen Reduction Reaction by N-Doped Mesoporous Carbon Nanospheres
Authors: Bita Bayatsarmadi, Shi-Zhang Qiao
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The development of ordered mesoporous carbon materials with controllable structures and improved physicochemical properties by doping heteroatoms such as nitrogen into the carbon framework has attracted a lot of attention, especially in relation to energy storage and conversion. Herein, a series of Nitrogen-doped mesoporous carbon spheres (NMC) was synthesized via a facile dual soft-templating procedure by tuning the nitrogen content and carbonization temperature. Various physical and (electro) chemical properties of the NMCs have been comprehensively investigated to pave the way for feasible design of nitrogen-containing porous carbon materials. The optimized sample showed a favorable electrocatalytic activity as evidenced by high kinetic current and positive onset potential for oxygen reduction reaction (ORR) due to its large surface area, high pore volume, good conductivity and high nitrogen content, which make it as a highly efficient ORR metal-free catalyst in alkaline solutions.Keywords: porous carbon, N-doping, oxygen reduction reaction, soft-template
Procedia PDF Downloads 2521612 Safety Profile of Anti-Retroviral Medicine in South Africa Based on Reported Adverse Drug Reactions
Authors: Sarah Gounden, Mukesh Dheda, Boikhutso Tlou, Elizabeth Ojewole, Frasia Oosthuizen
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Background: Antiretroviral therapy (ART) has been effective in the reduction of mortality and resulted in an improvement in the prognosis of HIV-infected patients. However, treatment with antiretrovirals (ARVs) has led to the development of many adverse drug reactions (ADRs). It is, therefore, necessary to determine the safety profile of these medicines in a South African population in order to ensure safe and optimal medicine use. Objectives: The aim of this study was to quantify ADRs experienced with the different ARVs currently used in South Africa, to determine the safety profile of ARV medicine in South Africa based on reported ADRs, and to determine the ARVs with the lowest risk profile based on specific patient populations. Methodology: This was a quantitative study. Individual case safety reports for the period January 2010 – December 2013 were obtained from the National Pharmacovigilance Center; these reports contained information on ADRs, ARV medicine, and patient demographics. Data was analysed to find associations that may exist between ADRs experienced, ARV medicines used and patient demographics. Results: A total of 1916 patient reports were received of which 1534 met the inclusion criteria for the study. The ARV with the lowest risk of ADRs were found to be lamivudine (0.51%, n=12), followed by lopinavir/ritonavir combination (0.8%, n=19) and abacavir (0.64%, n=15). A higher incidence of ADRs was observed in females compared to males. The age group 31–50 years and the weight group 61–80 kg had the highest incidence of ADRs reported. Conclusion: This study found that the safest ARVs to be used in a South African population are lamivudine, abacavir, and the lopinavir/ritonavir combination. Gender differences play a significant role in the occurrence of ADRs and both anatomical and physiological differences account for this. An increased BMI (body mass index) in both men and women showed an increase in the incidence of ADRs associated with ARV therapy.Keywords: adverse drug reaction, antiretrovirals, HIV/AIDS, pharmacovigilance, South Africa
Procedia PDF Downloads 3511611 Vascular Targeted Photodynamic Therapy Monitored by Real-Time Laser Speckle Imaging
Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz
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Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging
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