Search results for: medical treatment
7769 Improving Our Understanding of the in vivo Modelling of Psychotic Disorders
Authors: Zsanett Bahor, Cristina Nunes-Fonseca, Gillian L. Currie, Emily S. Sena, Lindsay D.G. Thomson, Malcolm R. Macleod
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Psychosis is ranked as the third most disabling medical condition in the world by the World Health Organization. Despite a substantial amount of research in recent years, available treatments are not universally effective and have a wide range of adverse side effects. Since many clinical drug candidates are identified through in vivo modelling, a deeper understanding of these models, and their strengths and limitations, might help us understand reasons for difficulties in psychosis drug development. To provide an unbiased summary of the preclinical psychosis literature we performed a systematic electronic search of PubMed for publications modelling a psychotic disorder in vivo, identifying 14,721 relevant studies. Double screening of 11,000 publications from this dataset so far established 2403 animal studies of psychosis, with the most common model being schizophrenia (95%). 61% of these models are induced using pharmacological agents. For all the models only 56% of publications test a therapeutic treatment. We propose a systematic review of these studies to assess the prevalence of reporting of measures to reduce risk of bias, and a meta-analysis to assess the internal and external validity of these animal models. Our findings are likely to be relevant to future preclinical studies of psychosis as this generation of strong empirical evidence has the potential to identify weaknesses, areas for improvement and make suggestions on refinement of experimental design. Such a detailed understanding of the data which inform what we think we know will help improve the current attrition rate between bench and bedside in psychosis research.Keywords: animal models, psychosis, systematic review, schizophrenia
Procedia PDF Downloads 2947768 Study the Multifaceted Therapeutic Properties of the IQGAP1shRNA Plasmid on Rat Liver Cancer Model
Authors: Khairy M. A. Zoheir, Nehma A. Ali, Ahmed M. Darwish, Mohamed S. Kishta, Ahmed A. Abd-Rabou, Mohamed A. Abdelhafez, Karima F. Mahrous
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The study comprehensively investigated the multifaceted therapeutic properties of the IQGAP1shRNA plasmid, encompassing its hepatoprotective, immunomodulatory, and anticancer activities. The study employed a Prednisolone-induced immunosuppressed rat model to assess the hepatoprotective and immunomodulatory effects of IQGAP1shRNA plasmid. Using this model, IQGAP1shRNA plasmid was found to modulate haematopoiesis, improving RBC, platelet, and WBC counts, underscoring its potential in hematopoietic homeostasis. Organ atrophy, a hallmark of immunosuppression in spleen, heart, liver, ovaries, and kidneys, was reversed with IQGAP1shRNA plasmid treatment, reinforcing its hepatotrophic and organotropic capabilities. Elevated hepatic biomarkers (ALT, AST, ALP, LPO) indicative of hepatocellular injury and oxidative stress were reduced with GST, highlighting its hepatoprotective and antioxidative effects. IQGAP1shRNA plasmid also restored depleted antioxidants (GSH and SOD), emphasizing its potent antioxidative and free radical scavenging capabilities. Molecular insights into immune dysregulation revealed downregulation of IQGAP1, IQGAP3 interleukin-2 (IL-2), and interleukin-4 (IL-4) mRNA expression in the liver of immunosuppressed rats. IL-2 and IL-4 play pivotal roles in immune regulation, T-cell activation, and B-cell differentiation. Notably, treatment with IQGAP1shRNA plasmid exhibited a significant upregulation of IL-2 and IL-4 mRNA expression, thereby accentuating its immunomodulatory potential in orchestrating immune homeostasis. Additionally, immune dysregulation was associated with increased levels of TNF-α. However, treatment with IQGAP1shRNA plasmid effectively decreased the levels of TNF-α, further underscoring its role in modulating inflammatory responses and restoring immune balance in immunosuppressed rats. Additionally, pharmacokinetics, bioavailability, drug-likeness, and toxicity risk assessment prediction suggest its potential as a pharmacologically favourable agent with no serious adverse effects. In conclusion, this study confirms the therapeutic potential of the IQGAP1shRNA plasmid, showcasing its effectiveness against hepatotoxicity, oxidative stress, immunosuppression, and its notable anticancer activity.Keywords: IQGAP1, shRNA, cancer, liver, rat
Procedia PDF Downloads 207767 Effect of Silicon Sulphate and Silicic Acid Rates on Growth, Yield and Nutritional Status of Wheat (Triticum aestivum L.)
Authors: R. G. Shemi, M. A. Abo Horish, Kh. M. A. Mekled
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The utilization of silicon (Si) sources is a crucial agricultural tool that requires optimization to promote sustainable practices. The application of Si provides the implementation of biological mechanisms of plant nutrition, growth promotion, and protection. The aims of this experiment were to investigate the relative efficacy of Si sources and levels on the growth, yield, and mineral content of wheat. The study examined the effects of silicon sulphate and silicic acid levels on growth, spike characteristics, yield parameters, and macro- and micronutrient concentrations of wheat during the 2-season. The entire above-indicated parameters were significantly (p < 0.05) increased with increasing levels of silicon sulphate and silicic acid compared to the control. Foliar application of silicon sulphate 150 ppm and silicic acid 60 ppm statistically (p < 0.05) enhanced grain N concentration and the grain yield by 136.14 and 77.85%, 43.49 and 34.52% in the 1st season, and by 78.62 and 54.40%, 43.53 and 33.18% in the 2nd season, respectively, as compared with control. Overall, foliar applications of silicon sulphate at 150 ppm and silicic acid at 60 ppm were greatly efficient amongst all Si levels and sources in improving growth and spike characters, increasing yield parameters, and elevating grain nutrients. Finally, the treatment of silicon sulfate at 150 ppm was more effective than the treatment of silicic acid at 60 ppm in increasing growth, grain nutrients, and productivity of wheat and attaining agricultural sustainability under experiment conditions.Keywords: wheat, silicon sulphate, silicic acid, grain nutrients
Procedia PDF Downloads 257766 The Effects of Metformin And PCL-sorafenib Nanoparticles Co-treatment on MCF-7 Cell Culture Model of Breast Cancer
Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad
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Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.Keywords: breast cancer, metformin, nanotechnology, sorafenib
Procedia PDF Downloads 827765 Human 3D Metastatic Melanoma Models for in vitro Evaluation of Targeted Therapy Efficiency
Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade
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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency
Procedia PDF Downloads 3077764 Discovery of New Inhibitors for Colorectal Cancer Treatment
Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang
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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1
Procedia PDF Downloads 2487763 Photocatalytic Degradation of Phenolic Compounds in Wastewater Using Magnetically Recoverable Catalyst
Authors: Ahmed K. Sharaby, Ahmed S. El-Gendy
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Phenolic compounds (PCs) exist in the wastewater effluents of some industries such as oil refinery, pharmaceutical and cosmetics. Phenolic compounds are extremely hazardous pollutants that can cause severe problems to the aquatic life and human beings if disposed of without treatment. One of the most efficient treatment methods of PCs is photocatalytic degradation. The current work studies the performance of composite nanomaterial of titanium dioxide with magnetite as a photo-catalyst in the degradation of PCs. The current work aims at optimizing the synthesized photocatalyst dosage and contact time as part of the operational parameters at different initial concentrations of PCs and pH values in the wastewater. The study was performed in a lab-scale batch reactor under fixed conditions of light intensity and aeration rate. The initial concentrations of PCs and the pH values were in the range of (10-200 mg/l) and (3-9), respectively. Results of the study indicate that the dosage of the catalyst and contact time for total mineralization is proportional to the initial concentrations of PCs, while the optimum pH conditions for highly efficient degradation is at pH 3. Exceeding the concentration levels of the catalyst beyond certain limits leads to the decrease in the degradation efficiency due to the dissipation of light. The performance of the catalyst for degradation was also investigated in comparison to the pure TiO2 Degussa (P-25). The dosage required for the synthesized catalyst for photocatalytic degradation was approximately 1.5 times that needed from the pure titania.Keywords: industrial, optimization, phenolic compounds, photocatalysis, wastewater
Procedia PDF Downloads 3217762 Effectiveness of Enhancing Positive Emotion Program of Patients with Lung Cancer
Authors: Pei-Fan Mu
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Background: Lung cancer is the most common cancer with the highest mortality rate. Patients with lung cancer under chemotherapy treatment experience life-threatening uncertainty. This study was based on the broaden-and-build theory using intentionality reflection of the body and internalization of positive prioritization strategies to enhance positive emotions of patients with lung cancer. Purpose: The purpose of this study was to use a quasi-experimental research design to examine the effectiveness of the enhancing positive emotion program. Method: Data were collected from a medical center in Taiwan. Fifty-four participants with lung cancer were recruited. Thirty participants were in the experiential group receiving the two weeks program. The content of the program includes awareness and understanding of the symptom experience, co-existing with illness and establishing self-identity, cognitive-emotion adjustment and establishing a new body schema, and symptom management to reach spiritual well-being. Twenty-four participants were in the control group receiving regular nursing care. Baseline, one month later and two months later, programmed measurements of symptoms of distress, positive emotion, and psychological well-being. Results: These two weeks of enhancing the positive emotion program resulted in a significantly improved positive emotion score for the experimental group compared to the control group. The findings of this study indicated that the positive emotion had significant differences between the two groups. There were no differences in symptom distress between the two groups. Discussion: The findings indicated that the enhancing positive emotion program could help patients enhance their life-threatening facing conditions.Keywords: positive emotion, lung cancer, experimental design, symptom distress
Procedia PDF Downloads 1037761 Improved Anatomy Teaching by the 3D Slicer Platform
Authors: Ahmedou Moulaye Idriss, Yahya Tfeil
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Medical imaging technology has become an indispensable tool in many branches of the biomedical, health area, and research and is vitally important for the training of professionals in these fields. It is not only about the tools, technologies, and knowledge provided but also about the community that this training project proposes. In order to be able to raise the level of anatomy teaching in the medical school of Nouakchott in Mauritania, it is necessary and even urgent to facilitate access to modern technology for African countries. The role of technology as a key driver of justifiable development has long been recognized. Anatomy is an essential discipline for the training of medical students; it is a key element for the training of medical specialists. The quality and results of the work of a young surgeon depend on his better knowledge of anatomical structures. The teaching of anatomy is difficult as the discipline is being neglected by medical students in many academic institutions. However, anatomy remains a vital part of any medical education program. When anatomy is presented in various planes medical students approve of difficulties in understanding. They do not increase their ability to visualize and mentally manipulate 3D structures. They are sometimes not able to correctly identify neighbouring or associated structures. This is the case when they have to make the identification of structures related to the caudate lobe when the liver is moved to different positions. In recent decades, some modern educational tools using digital sources tend to replace old methods. One of the main reasons for this change is the lack of cadavers in laboratories with poorly qualified staff. The emergence of increasingly sophisticated mathematical models, image processing, and visualization tools in biomedical imaging research have enabled sophisticated three-dimensional (3D) representations of anatomical structures. In this paper, we report our current experience in the Faculty of Medicine in Nouakchott Mauritania. One of our main aims is to create a local learning community in the fields of anatomy. The main technological platform used in this project is called 3D Slicer. 3D Slicer platform is an open-source application available for free for viewing, analysis, and interaction with biomedical imaging data. Using the 3D Slicer platform, we created from real medical images anatomical atlases of parts of the human body, including head, thorax, abdomen, liver, and pelvis, upper and lower limbs. Data were collected from several local hospitals and also from the website. We used MRI and CT-Scan imaging data from children and adults. Many different anatomy atlases exist, both in print and digital forms. Anatomy Atlas displays three-dimensional anatomical models, image cross-sections of labelled structures and source radiological imaging, and a text-based hierarchy of structures. Open and free online anatomical atlases developed by our anatomy laboratory team will be available to our students. This will allow pedagogical autonomy and remedy the shortcomings by responding more fully to the objectives of sustainable local development of quality education and good health at the national level. To make this work a reality, our team produced several atlases available in our faculty in the form of research projects.Keywords: anatomy, education, medical imaging, three dimensional
Procedia PDF Downloads 2477760 The Nursing Experience for an Intestinal Perforation Elderly with a Temporary Enterostomy
Authors: Hsiu-Chuan Hsueh, Kuei-Feng Shen Jr., Chia-Ling Chao, Hui-Chuan Pan
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This article described a 75 years old woman who has suffered from intestinal perforation and accepted surgery with temporary enterostomy, the operation makes her depressed, refused relatives and friend's care, facing low willingness to participate in various activities due to fear of changing body appearance caused by surgery and leave enterostomy. The author collected information through observation talks, physical evaluation, and medical records during the period of care from November 14 to November 30, 2016, we used the four aspects of physiology, psychology, society and spirituality as a whole sexual assessment to establish the nursing problems of patient, included of acute pain, disturbance of body image,coping ineffective individual. For patient care issues, to encouraged case to express their inner feelings and take part in self-care programs through providing good therapeutic interpersonal relationships with their families. However, it provided clear information about the disease and follow-up treatment plan, give compliments in a timely manner, enhanced self-confidence of individual cases and their motivation to participate in self-care of stoma, further face the disease in a positive manner. At the same time, cross-section team care model and individual care measures were developed to enhance the care skills after returning home and at the same time assist the individual in facing the psychological impact caused by stoma. Hope to provide this experience, as a reference for the future care of the disease.Keywords: enterostomy, intestinal perforation, nursing experience, ostomy
Procedia PDF Downloads 1417759 The Impact of COVID-19 on the Mental Health of Residents of Saudi Arabia
Authors: Khaleel Alyahya, Faizah Alotaibi
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The coronavirus disease 19 (COVID-19) pandemic has caused an increase in general fear and anxiety around the globe. With the public health measures, including lockdown and travel restrictions, the COVID-19 period further resulted in a sudden increase in the vulnerability of people too ill mental health. This becomes greater among individuals who have a history of mental illness or are undergoing treatment and do not have easy access to medication and medical consultations. The study aims to measure the impact of COVID-19 and the degree of distress with the DASS scale on the mental health of residents living in Saudi Arabia. The study is a quantitative, observational, and cross-sectional conducted in Saudi Arabia to measure the impact of COVID-19 on the mental health of both citizens and residents of Saudi Arabia during pandemics. The study ran from February 2021 to June 2021, and a validated questionnaire was used. The targeted population of the study was Saudi citizens and non-Saudi residents. A sample size of 800 participants was calculated with a single proportion formula at 95% level of significance and 5% allowable error. The result revealed that participants who were always doing exercise experienced the lowest level of depression, anxiety, and stress. The highest prevalence of severe and extremely severe depression was among participants who sometimes do exercise at 53.2% for each. Similar results were obtained for anxiety and stress, where the extremely severe form was reported by those who sometimes did exercise at 54.8% and 72.2%, respectively. There was an inverse association between physical activity levels and levels of depression, anxiety, and stress during the COVID-19. Similarly, the levels of depression, anxiety, and stress differed significantly according to the exercise frequency during COVID-19.Keywords: mental, COVID-19, pandemic, lockdown, depression, anxiety, stress
Procedia PDF Downloads 1077758 Effect of Sweet Potato (Ipomoea batatas) Leaves on Wheat Offal Replacement for Chicks Feed Production
Authors: C. C. Okafor, T. M. Ezeh
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The effect of addition of sweet potato leaves in replacement of wheat offal in the production of broiler chicks feed was studied. 72 day-old marshal strain chicks were used and brooded for two weeks with a normal commercial feed in Nigeria called top feed and weighed separately at the end of the two weeks, complete randomized design (CRD) was used. The weighed broiler chicks were randomly allocated to four dietary treatments. Each treatment was replicated to twice with eighteen birds per replicate. The four dietary treatment identified as T1, T2, T3 and T4. T1 served as control diet with 21% crude protein content, while T2 was prepared with Enzyme and in T3 and T4, wheat offal was replaced with sweet potato leaves and in T4 with inclusion of enzyme. Growth performance was studied using the following daily feed intake, daily weight gain and feed efficiency. The result in daily weight gain showed that chicks fed with T2 feed had the highest weight gain (93.75) while chicks fed with T3 had the least weight gain of (34.5 gm). In daily feed intake chicks fed with T4 fed more (53.06 gm) than chicks fed with T2 (51.08 gm). In feed efficiency T3 had the highest value of 30% while the T2 had the least efficiency of 22%. There was no significant difference (P≥ 0.05) in all the three parameter tested. Sweet potato leaves can replace wheat offal in broiler feed production without any adverse effect on the growth performance.Keywords: broiler, diet, dietary, potato leaves, wheat offal
Procedia PDF Downloads 5387757 Mental Health and the Criminal Justice System: A Review on the Mental Health Diversion Programs and Their Effectiveness in Reducing Recidivism
Authors: Lianyan Zhou
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According to the National Conference of State Legislatures, a person experiencing a mental health crisis is more likely to encounter law enforcement than crisis intervention or treatment. People with mental illness are overrepresented in incarceration, often resulting in exacerbation of the symptoms and increasing the likelihood of recidivism and rearrest. To address the issue of the large number of people with mental illness cycling through the criminal justice system, mental health courts and diversion programs were established. Mental health diversion programs are considered as more appropriate options for offenders whose mental illness is significantly contributing to their criminal offenses. However, these programs are controversial, with criticism that offenders may view the programs as the only to get treatment or to avoid jail time. This paper provides a comprehensive review of the effectiveness of mental health diversion programs. More specifically, it examines how these programs may reduce recidivism compared to incarceration. Materials presented in this review were selected from forensic and general psychology journals. Additional policy documents, government reports, and court records are also included for discussion. The results suggest that mental health diversion programs are overall more successful in intervening compared to incarcerations. The recidivism rates for program participants are lower. However, individual factors do contribute to the outcome of the programs.Keywords: diversion programs, forensic psychology, justice system, mental health courts, mental illness, rearrest, recidivism
Procedia PDF Downloads 227756 A Comparison of Methods for Estimating Dichotomous Treatment Effects: A Simulation Study
Authors: Jacqueline Y. Thompson, Sam Watson, Lee Middleton, Karla Hemming
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Introduction: The odds ratio (estimated via logistic regression) is a well-established and common approach for estimating covariate-adjusted binary treatment effects when comparing a treatment and control group with dichotomous outcomes. Its popularity is primarily because of its stability and robustness to model misspecification. However, the situation is different for the relative risk and risk difference, which are arguably easier to interpret and better suited to specific designs such as non-inferiority studies. So far, there is no equivalent, widely acceptable approach to estimate an adjusted relative risk and risk difference when conducting clinical trials. This is partly due to the lack of a comprehensive evaluation of available candidate methods. Methods/Approach: A simulation study is designed to evaluate the performance of relevant candidate methods to estimate relative risks to represent conditional and marginal estimation approaches. We consider the log-binomial, generalised linear models (GLM) with iteratively weighted least-squares (IWLS) and model-based standard errors (SE); log-binomial GLM with convex optimisation and model-based SEs; log-binomial GLM with convex optimisation and permutation tests; modified-Poisson GLM IWLS and robust SEs; log-binomial generalised estimation equations (GEE) and robust SEs; marginal standardisation and delta method SEs; and marginal standardisation and permutation test SEs. Independent and identically distributed datasets are simulated from a randomised controlled trial to evaluate these candidate methods. Simulations are replicated 10000 times for each scenario across all possible combinations of sample sizes (200, 1000, and 5000), outcomes (10%, 50%, and 80%), and covariates (ranging from -0.05 to 0.7) representing weak, moderate or strong relationships. Treatment effects (ranging from 0, -0.5, 1; on the log-scale) will consider null (H0) and alternative (H1) hypotheses to evaluate coverage and power in realistic scenarios. Performance measures (bias, mean square error (MSE), relative efficiency, and convergence rates) are evaluated across scenarios covering a range of sample sizes, event rates, covariate prognostic strength, and model misspecifications. Potential Results, Relevance & Impact: There are several methods for estimating unadjusted and adjusted relative risks. However, it is unclear which method(s) is the most efficient, preserves type-I error rate, is robust to model misspecification, or is the most powerful when adjusting for non-prognostic and prognostic covariates. GEE estimations may be biased when the outcome distributions are not from marginal binary data. Also, it seems that marginal standardisation and convex optimisation may perform better than GLM IWLS log-binomial.Keywords: binary outcomes, statistical methods, clinical trials, simulation study
Procedia PDF Downloads 1187755 Simulation of X-Ray Tissue Contrast and Dose Optimisation in Radiological Physics to Improve Medical Imaging Students’ Skills
Authors: Peter J. Riley
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Medical Imaging students must understand the roles of Photo-electric Absorption (PE) and Compton Scatter (CS) interactions in patients to enable optimal X-ray imaging in clinical practice. A simulator has been developed that shows relative interaction probabilities, color bars for patient dose from PE, % penetration to the detector, and obscuring CS as Peak Kilovoltage (kVp) changes. Additionally, an anthropomorphic chest X-ray image shows the relative tissue contrasts and overlying CS-fog at that kVp, which determine the detectability of a lesion in the image. A series of interactive exercises with MCQs evaluate the student's understanding; the simulation has improved student perception of the need to acquire "sufficient" rather than maximal contrast to enable patient dose reduction at higher kVp.Keywords: patient dose optimization, radiological physics, simulation, tissue contrast
Procedia PDF Downloads 1037754 Effect of Antioxidants Addition in Combination with Milk Re Pasteurization on the Physical, Chemical and Sensory Properties of Condensed Yoghurt
Authors: Mahmoud Abu-Ghoush, Murad Al Holy
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Our main goal in this project is to study the causes and finding solutions for both the hydrolytic and the oxidative rancidity that can be produced during condensed yoghurt production. The re pasteurization of the pasteurized milk and the addition of different types of antioxidants (ascorbic acid and propyl gallate) were used to achieve this goal. Chemical, physical, microbial and sensory tests were done to evaluate the product. It was found that there were significant differences between the different treatments and the control regarding the peroxide value. This means that the addition of both types of antioxidants have a positive effect in decreasing the rancidity value. However, it was found that there were some samples have hydrolytic rancidity flavour without any type of oxidative rancidity (low peroxide value). To overcome this problem the re pasteurization step was used to destroy all the vegetative form of microbes. It was found that this treatment was very useful in controlling the rancidity flavour according to the sensory evaluation of the condensed yoghurt products for several batches. The best condensed yoghurt which contains 0.25% ascorbic acid exhibited the highest sensory properties values. Also, it has the ability in lowering the oxidative rancidity in the combination with the re pasteurization step of the pasteurized milk. This suggests that a higher quality and stable condensed yoghurt can be obtained upon using this combination. These results may help producers in selecting the best treatment methods to overcome the rancidity flavor in this type of condensed yoghurt.Keywords: antioxidants, condensed yoghurt, repasturization, condensed milk
Procedia PDF Downloads 2907753 Multi-Omics Integrative Analysis Coupled to Control Theory and Computational Simulation of a Genome-Scale Metabolic Model Reveal Controlling Biological Switches in Human Astrocytes under Palmitic Acid-Induced Lipotoxicity
Authors: Janneth Gonzalez, Andrés Pinzon Velasco, Maria Angarita
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Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatorypathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, broad studies with a systemic point of view on the neurodegenerative role of PA and the neuro-protective mechanisms of tibolone are lacking. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also applied a control theory approach to identify those reactions that exert more control in the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a switch in energy source use through inhibition of folate cycle and fatty acid β‐oxidation and upregulation of ketone bodies formation. We found 25 metabolic switches under PA‐mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation of metabolic pathways that may increase neurotoxicity and represent potential treatment targets. Finally, the overall framework of our approach facilitates the understanding of complex metabolic regulation, and it can be used for in silico exploration of the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics
Procedia PDF Downloads 1027752 The Scope and Effectiveness of Interactive Voice Response Technologies in Post-Operative Care
Authors: Zanib Nafees, Amir Razaghizad, Ibtisam Mahmoud, Abhinav Sharma, Renzo Cecere
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More than one million surgeries are performed each year in Canada, resulting in more than 100,000 associated serious adverse events (SAEs) per year. These are defined as unintended injuries or complications that adversely affect the well-being of patients. In recent years, there has been a proliferation of digital health interventions that have the potential to assist, monitor, and educate patients—facilitating self-care following post-operative discharge. Among digital health, interventions are interactive-voice response technologies (IVRs), which have been shown to be highly effective in certain medical settings. Although numerous IVR-based interventions have been developed, their effectiveness and utility remain unclear, notably in post-operative settings. To the best of our knowledge, no systematic or scoping reviews have evaluated this topic to date. Thus, the objective of this scoping review protocol is to systematically map and explore the literature and evidence describing and examining IVR tools, implementation, evaluation, outcome, and experience for post-operative patients. The focus will be primarily on the evaluation of baseline performance status, clinical assessment, treatment outcomes, and patient management, including self-management and self-monitoring. The objective of this scoping review is to assess the extent of the literature to direct future research efforts by identifying gaps and limitations in the literature and to highlight relevant determinants of positive outcomes in the emerging field of IVR monitoring for health outcomes in post-operative patients.Keywords: digital healthcare technologies, post-surgery, interactive voice technology, interactive voice response
Procedia PDF Downloads 2707751 Text Mining Past Medical History in Electrophysiological Studies
Authors: Roni Ramon-Gonen, Amir Dori, Shahar Shelly
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Background and objectives: Healthcare professionals produce abundant textual information in their daily clinical practice. The extraction of insights from all the gathered information, mainly unstructured and lacking in normalization, is one of the major challenges in computational medicine. In this respect, text mining assembles different techniques to derive valuable insights from unstructured textual data, so it has led to being especially relevant in Medicine. Neurological patient’s history allows the clinician to define the patient’s symptoms and along with the result of the nerve conduction study (NCS) and electromyography (EMG) test, assists in formulating a differential diagnosis. Past medical history (PMH) helps to direct the latter. In this study, we aimed to identify relevant PMH, understand which PMHs are common among patients in the referral cohort and documented by the medical staff, and examine the differences by sex and age in a large cohort based on textual format notes. Methods: We retrospectively identified all patients with abnormal NCS between May 2016 to February 2022. Age, gender, and all NCS attributes reports were recorded, including the summary text. All patients’ histories were extracted from the text report by a query. Basic text cleansing and data preparation were performed, as well as lemmatization. Very popular words (like ‘left’ and ‘right’) were deleted. Several words were replaced with their abbreviations. A bag of words approach was used to perform the analyses. Different visualizations which are common in text analysis, were created to easily grasp the results. Results: We identified 5282 unique patients. Three thousand and five (57%) patients had documented PMH. Of which 60.4% (n=1817) were males. The total median age was 62 years (range 0.12 – 97.2 years), and the majority of patients (83%) presented after the age of forty years. The top two documented medical histories were diabetes mellitus (DM) and surgery. DM was observed in 16.3% of the patients, and surgery at 15.4%. Other frequent patient histories (among the top 20) were fracture, cancer (ca), motor vehicle accident (MVA), leg, lumbar, discopathy, back and carpal tunnel release (CTR). When separating the data by sex, we can see that DM and MVA are more frequent among males, while cancer and CTR are less frequent. On the other hand, the top medical history in females was surgery and, after that, DM. Other frequent histories among females are breast cancer, fractures, and CTR. In the younger population (ages 18 to 26), the frequent PMH were surgery, fractures, trauma, and MVA. Discussion: By applying text mining approaches to unstructured data, we were able to better understand which medical histories are more relevant in these circumstances and, in addition, gain additional insights regarding sex and age differences. These insights might help to collect epidemiological demographical data as well as raise new hypotheses. One limitation of this work is that each clinician might use different words or abbreviations to describe the same condition, and therefore using a coding system can be beneficial.Keywords: abnormal studies, healthcare analytics, medical history, nerve conduction studies, text mining, textual analysis
Procedia PDF Downloads 1017750 Formulation and Evaluation of Lisinopril Microspheres for Nasal Delivery
Authors: S. S. Patil, R. M. Mhetre, S. V. Patil
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Lisinopril is an angiotensin converting enzyme inhibitor used in the treatment of hypertension and heart failure in prophylactic treatment after myocardial infarction and in diabetic nephropathy. However, it is very poorly absorbed from gastro-intestinal tract. Intranasal administration is an ideal alternative to the parenteral route for systemic drug delivery. Formulating multiparticulate system with mucoadhesive polymers provide a significant increase in the nasal residence time. The aim of the present approach was to overcome the drawbacks of the conventional dosage forms of lisinopril by formulating intranasal microspheres with Carbopol 974P NF and HPMC K4 M along with film forming polymer ethyl cellulose.The microspheres were prepared by emulsion solvent evaporation method. The prepared microspheres were characterized for encapsulation efficiency, drug loading, particle size, and surface morphology, degree of swelling, ex vivo mucoadhesion, drug release, ex vivo diffusion studies. All formulations has shown entrapment efficiency between 80 to more than 95%, mucoadhesion was more than 80 % and drug release up to 90 %. Ex vivo studies revealed tht the improved bioavailability of drug compared to oral drug administration. Both in vitro and in vivo studies conclude that combination of Carbopol and HPMC based microspheres shown better results than single carbopol based microspheres for the delivery of lisinopril.Keywords: microspheres, lisinopril, nasal delivery, solvent evaporation method
Procedia PDF Downloads 5327749 Experimental Investigation on Freeze-Concentration Process Desalting for Highly Saline Brines
Authors: H. Al-Jabli
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Using the freeze-melting process for the disposing of high saline brines was the aim of the paper by confirming the performance estimation of the treatment system. A laboratory bench scale freezing technique test unit was designed, constructed, and tested at Doha Research Plant (DRP) in Kuwait. The principal unit operations that have been considered for the laboratory study are: ice crystallization, separation, washing, and melting. The applied process is characterized as “the secondary-refrigerant indirect freezing”, which is utilizing normal freezing concept. The high saline brine was used as definite feed water, i.e. average TDS of 250,000 ppm. Kuwait desalination plants were carried out in the experimental study to measure the performance of the proposed treatment system. Experimental analysis shows that the freeze-melting process is capable of dropping the TDS of the feed water from 249,482 ppm to 56,880 ppm of the freeze-melting process in the two-phase’s course, whereas overall recovery results of the salt passage and salt rejection are 31.11%, 19.05%, and 80.95%, correspondingly. Therefore, the freeze-melting process is encouraging for the proposed application, as it shows on the results, which approves the process capability of reducing a major amount of the dissolved salts of the high saline brine with reasonable sensible recovery. This process might be reasonable with other brine disposal processes.Keywords: high saline brine, freeze-melting process, ice crystallization, brine disposal process
Procedia PDF Downloads 2797748 Effect of Probiotics and Vitamin B on Plasma Interferon-Gamma and Interleukin-6 Levels in Active Pulmonary Tuberculosis
Authors: Yulistiani Yulistiani, Zamrotul Izzah, Lintang Bismantara, Wenny Putri Nilamsari, Arif Bachtiar, Budi Suprapti
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Interferon-gamma (IFN-γ) and interleukin-6 (IL-6) are pro-inflammatory cytokines, which have the protective immune response against Tuberculosis (TB). Indeed, pro-inflammatory cytokines Mycobacterium tuberculosis antigen-specific CD4+ and CD8+ T cells and NK cells increase the level of production of IFN-γ, a cytokine critical for augmenting the microbicidal activity of phagocytes. On the other hand, M. tuberculosis reduces the effects of IFN-γ by inhibiting the transcription of IFN-γ- responsive genes and by inducing the secretion of IL-6, which inhibits IFN-γ signaling. Probiotics Lactobacillus sp. and Bifidobacterium sp. were known to increase IFN-γ production in vivo, while vitamin B1, B6, and B12 worked on macrophages and releasing cytokines. Therefore, the present study was to evaluate the effect of probiotics and vitamin B supplement on changes of plasma cytokine levels in active pulmonary TB. From October to November 2016, twelve M. tuberculosis-infected patients starting anti-TB drugs were recruited, then divided into two groups. Seven patients were given a combination of probiotics and vitamin B, while five patients were in the control group. Plasma IFN-γ and IL-6 levels were measured by the ELISA kit before and a month after treatment. IFN-γ levels raised in four patients receiving the supplement (P = 0.743), while IL-6 increased in three patients in this group until day 30 of treatment (P = 0.298). Taken together, these results show the promising effect of probiotics and vitamin B on stimulation of IFN-γ and IL-6 production during intensive therapy of TB.Keywords: interferon-gamma, interleukin-6, probiotic, tuberculosis
Procedia PDF Downloads 3527747 Tempo-Spatial Pattern of Progress and Disparity in Child Health in Uttar Pradesh, India
Authors: Gudakesh Yadav
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Uttar Pradesh is one of the poorest performing states of India in terms of child health. Using data from the three round of NFHS and two rounds of DLHS, this paper attempts to examine tempo-spatial change in child health and care practices in Uttar Pradesh and its regions. Rate-ratio, CI, multivariate, and decomposition analysis has been used for the study. Findings demonstrate that child health care practices have improved over the time in all regions of the state. However; western and southern region registered the lowest progress in child immunization. Nevertheless, there is no decline in prevalence of diarrhea and ARI over the period, and it remains critically high in the western and southern region. These regions also poorly performed in giving ORS, diarrhoea and ARI treatment. Public health services are least preferred for diarrhoea and ARI treatment. Results from decomposition analysis reveal that rural area, mother’s illiteracy and wealth contributed highest to the low utilization of the child health care practices consistently over the period of time. The study calls for targeted intervention for vulnerable children to accelerate child health care service utilization. Poor performing regions should be targeted and routinely monitored on poor child health indicators.Keywords: Acute Respiratory Infection (ARI), decomposition, diarrhea, inequality, immunization
Procedia PDF Downloads 3047746 Effect of Garlic Powder Extract on Fungi Isolated from Diseased Irish Potato in Bokkos, Plateau State Nigeria
Authors: Musa Filibus Gugu
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An investigation was carried out on the effect of garlic powder extract on fungi associated with Irish potato rot in Bokkos, Plateau State, Nigeria. Diseased Irish potatoes were randomly collected from three markets in the study location and fungal species isolated. Isolated fungal species were Fusarium culmorum, Fusarium oxysporum, and Pytophthora infestans. Frequency of occurrence for Fusarium culmorum, Fusarium oxysporum, and Pytophthora infestans was 10%, 34%, and 56%, respectively, using sabauraud dextrose agar, after incubation for 4-7 days. Treatment of Pytophthora infestans with garlic powder extract at concentrations of 0.5g/ml, 0.4g/ml, 0.3gml, 0.2g/ml and 0.1g/ml showed 100%, 92%, 68%, 32% and 10% inhibition zones, respectively. Fusarium culmorum showed 100%, 90%, 40%, 9% and 0% inhibition zones when treated with garlic powder extract at concentrations of 0.5g/ml, 0.4g/ml, 0.3gml, 0.2g/ml and 0.1g/ml, respectively. Garlic powder extract concentrations of 0.5g/ml, 0.4g/ml, 0.3gml, 0.2g/ml and 0.1g/ml showed 100%, 98%, 55%, 30%, 0% inhibition zones, respectively on Fusarium oxysporum. Hence, Restriction of the radial growth of the fungal colonies suggests a good antifungal effect of garlic extract. This can be integrated into the treatment of fungal diseases of Irish potato in Bokkos, Nigeria, as this will help to reduce the indiscriminate use of fungicides, especially in an environment with a struggling economy.Keywords: fungal rot, garlic extract, inhibition zone, Irish potato
Procedia PDF Downloads 1497745 Deep Feature Augmentation with Generative Adversarial Networks for Class Imbalance Learning in Medical Images
Authors: Rongbo Shen, Jianhua Yao, Kezhou Yan, Kuan Tian, Cheng Jiang, Ke Zhou
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This study proposes a generative adversarial networks (GAN) framework to perform synthetic sampling in feature space, i.e., feature augmentation, to address the class imbalance problem in medical image analysis. A feature extraction network is first trained to convert images into feature space. Then the GAN framework incorporates adversarial learning to train a feature generator for the minority class through playing a minimax game with a discriminator. The feature generator then generates features for minority class from arbitrary latent distributions to balance the data between the majority class and the minority class. Additionally, a data cleaning technique, i.e., Tomek link, is employed to clean up undesirable conflicting features introduced from the feature augmentation and thus establish well-defined class clusters for the training. The experiment section evaluates the proposed method on two medical image analysis tasks, i.e., mass classification on mammogram and cancer metastasis classification on histopathological images. Experimental results suggest that the proposed method obtains superior or comparable performance over the state-of-the-art counterparts. Compared to all counterparts, our proposed method improves more than 1.5 percentage of accuracy.Keywords: class imbalance, synthetic sampling, feature augmentation, generative adversarial networks, data cleaning
Procedia PDF Downloads 1337744 Formulation and Evaluation of Curcumin-Zn (II) Microparticulate Drug Delivery System for Antimalarial Activity
Authors: M. R. Aher, R. B. Laware, G. S. Asane, B. S. Kuchekar
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Objective: Studies have shown that a new combination therapy with Artemisinin derivatives and curcumin is unique, with potential advantages over known ACTs. In present study an attempt was made to prepare microparticulate drug delivery system of Curcumin-Zn complex and evaluate it in combination with artemether for antimalarial activity. Material and method: Curcumin Zn complex was prepared and encapsulated using sodium alginate. Microparticles thus obtained are further coated with various enteric polymers at different coating thickness to control the release. Microparticles are evaluated for encapsulation efficiency, drug loading and in vitro drug release. Roentgenographic Studies was conducted in rabbits with BaSO 4 tagged formulation. Optimized formulation was screened for antimalarial activity using P. berghei-infected mice survival test and % paracetemia inhibition, alone (three oral dose of 5mg/day) and in combination with arthemether (i.p. 500, 1000 and 1500µg). Curcumin-Zn(II) was estimated in serum after oral administration to rats by using spectroflurometry. Result: Microparticles coated with Cellulose acetate phthalate showed most satisfactory and controlled release with 479 min time for 60% drug release. X-ray images taken at different time intervals confirmed the retention of formulation in GI tract. Estimation of curcumin in serum by spectroflurometry showed that drug concentration is maintained in the blood for longer time with tmax of 6 hours. The survival time (40 days post treatment) of mice infected with P. berghei was compared to survival after treatment with either Curcumin-Zn(II) microparticles artemether combination, curcumin-Zn complex and artemether. Oral administration of Curcumin-Zn(II)-artemether prolonged the survival of P.berghei-infected mice. All the mice treated with Curcumin-Zn(II) microparticles (5mg/day) artemether (1000µg) survived for more than 40 days and recovered with no detectable parasitemia. Administration of Curcumin-Zn(II) artemether combination reduced the parasitemia in mice by more than 90% compared to that in control mice for the first 3 days after treatment. Conclusion: Antimalarial activity of the curcumin Zn-artemether combination was more pronounced than mono therapy. A single dose of 1000µg of artemether in curcumin-Zn combination gives complete protection in P. berghei-infected mice. This may reduce the chances of drug resistance in malaria management.Keywords: formulation, microparticulate drug delivery, antimalarial, pharmaceutics
Procedia PDF Downloads 3977743 A Case Study of Low Head Hydropower Opportunities at Existing Infrastructure in South Africa
Authors: Ione Loots, Marco van Dijk, Jay Bhagwan
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Historically, South Africa had various small-scale hydropower installations in remote areas that were not incorporated in the national electricity grid. Unfortunately, in the 1960s most of these plants were decommissioned when Eskom, the national power utility, rapidly expanded its grid and capability to produce cheap, reliable, coal-fired electricity. This situation persisted until 2008, when rolling power cuts started to affect all citizens. This, together with the rising monetary and environmental cost of coal-based power generation, has sparked new interest in small-scale hydropower development, especially in remote areas or at locations (like wastewater treatment works) that could not afford to be without electricity for long periods at a time. Even though South Africa does not have the same, large-scale, hydropower potential as some other African countries, significant potential for micro- and small-scale hydropower is hidden in various places. As an example, large quantities of raw and potable water are conveyed daily under either pressurized or gravity conditions over large distances and elevations. Due to the relative water scarcity in the country, South Africa also has more than 4900 registered dams of varying capacities. However, institutional capacity and skills have not been maintained in recent years and therefore the identification of hydropower potential, as well as the development of micro- and small-scale hydropower plants has not gained significant momentum. An assessment model and decision support system for low head hydropower development has been developed to assist designers and decision makers with first-order potential analysis. As a result, various potential sites were identified and many of these sites were situated at existing infrastructure like weirs, barrages or pipelines. One reason for the specific interest in existing infrastructure is the fact that capital expenditure could be minimized and another is the reduced negative environmental impact compared to greenfield sites. This paper will explore the case study of retrofitting an unconventional and innovative hydropower plant to the outlet of a wastewater treatment works in South Africa.Keywords: low head hydropower, retrofitting, small-scale hydropower, wastewater treatment works
Procedia PDF Downloads 2567742 Classification of Multiple Cancer Types with Deep Convolutional Neural Network
Authors: Nan Deng, Zhenqiu Liu
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Thousands of patients with metastatic tumors were diagnosed with cancers of unknown primary sites each year. The inability to identify the primary cancer site may lead to inappropriate treatment and unexpected prognosis. Nowadays, a large amount of genomics and transcriptomics cancer data has been generated by next-generation sequencing (NGS) technologies, and The Cancer Genome Atlas (TCGA) database has accrued thousands of human cancer tumors and healthy controls, which provides an abundance of resource to differentiate cancer types. Meanwhile, deep convolutional neural networks (CNNs) have shown high accuracy on classification among a large number of image object categories. Here, we utilize 25 cancer primary tumors and 3 normal tissues from TCGA and convert their RNA-Seq gene expression profiling to color images; train, validate and test a CNN classifier directly from these images. The performance result shows that our CNN classifier can archive >80% test accuracy on most of the tumors and normal tissues. Since the gene expression pattern of distant metastases is similar to their primary tumors, the CNN classifier may provide a potential computational strategy on identifying the unknown primary origin of metastatic cancer in order to plan appropriate treatment for patients.Keywords: bioinformatics, cancer, convolutional neural network, deep leaning, gene expression pattern
Procedia PDF Downloads 3047741 Exploiting the Tumour Microenvironment in Order to Optimise Sonodynamic Therapy for Cancer
Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou
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Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound
Procedia PDF Downloads 1437740 Blockchain-Based Decentralized Architecture for Secure Medical Records Management
Authors: Saeed M. Alshahrani
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This research integrated blockchain technology to reform medical records management in healthcare informatics. It was aimed at resolving the limitations of centralized systems by establishing a secure, decentralized, and user-centric platform. The system was architected with a sophisticated three-tiered structure, integrating advanced cryptographic methodologies, consensus algorithms, and the Fast Healthcare Interoperability Resources (HL7 FHIR) standard to ensure data security, transaction validity, and semantic interoperability. The research has profound implications for healthcare delivery, patient care, legal compliance, operational efficiency, and academic advancements in blockchain technology and healthcare IT sectors. The methodology adapted in this research comprises of Preliminary Feasibility Study, Literature Review, Design and Development, Cryptographic Algorithm Integration, Modeling the data and testing the system. The research employed a permissioned blockchain with a Practical Byzantine Fault Tolerance (PBFT) consensus algorithm and Ethereum-based smart contracts. It integrated advanced cryptographic algorithms, role-based access control, multi-factor authentication, and RESTful APIs to ensure security, regulate access, authenticate user identities, and facilitate seamless data exchange between the blockchain and legacy healthcare systems. The research contributed to the development of a secure, interoperable, and decentralized system for managing medical records, addressing the limitations of the centralized systems that were in place. Future work will delve into optimizing the system further, exploring additional blockchain use cases in healthcare, and expanding the adoption of the system globally, contributing to the evolution of global healthcare practices and policies.Keywords: healthcare informatics, blockchain, medical records management, decentralized architecture, data security, cryptographic algorithms
Procedia PDF Downloads 58