Search results for: Abigail F. Ruby
25 Therapeutic Potential of mAb KP52 in Human and Feline Cancers
Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo
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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.Keywords: ADC, comparative oncology, mAb, therapeutic
Procedia PDF Downloads 17424 Application of Scoring Rubrics by Lecturers towards Objective Assessment of Essay Questions in the Department of Social Science Education, University of Calabar, Nigeria
Authors: Donald B. Enu, Clement O. Ukpor, Abigail E. Okon
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Unreliable scoring of students’ performance by lecturers short-chains students’ assessment in terms of underequipping the school authority with facts as intended by society through the curriculum hence, the learners, the school and the society are cheated because the usefulness of testing is defeated. This study, therefore, examined lecturers’ scoring objectivity of essay items in the Department of Social Science Education, University of Calabar, Nigeria. Specifically, it assessed lecturers’ perception of the relevance of scoring rubrics and its level of application. Data were collected from all the 36 lecturers in the Department (28 members and 8 non-members adjourned to the department), through a 20-item questionnaire and checklist instruments. A case-study design was adopted. Descriptive statistics of frequency counts, weighted means, standard deviations, and percentages were used to analyze data gathered. A mean score of 2.5 and or 60 percent and above formed the acceptance or significant level in decision taking. It was found that lecturers perceived the use of scoring rubrics as a relevant practice to ensure fairness and reliable treatment of examiners scripts particularly in marking essay items and that there is a moderately high level of adherence to the application of scoring rubrics. It was also observed that some criteria necessary for the scoring objectivity of essay items were not fully put in place in the department. It was recommended strongly that students’ identities be hidden while marking and that pre-determined marking scheme should be prepared centrally and strictly adhered to during marking and recording of scores. Conference marking should be enforced in the department.Keywords: essay items, objective scoring, scorers reliability, scoring rubrics
Procedia PDF Downloads 18123 Oxidation States of Trace Elements in Synthetic Corundum
Authors: Ontima Yamchuti, Waruntorn Kanitpanyacharoen, Chakkaphan Sutthirat, Wantana Klysuban, Penphitcha Amonpattarakit
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Natural corundum occurs in various colors due to impurities or trace elements in its structure. Sapphire and ruby are essentially the same mineral, corundum, but valued differently due to their red and blue varieties, respectively. Color is one of the critical factors used to determine the value of natural and synthetic corundum. Despite the abundance of research on impurities in natural corundum, little is known about trace elements in synthetic corundum. This project thus aims to quantify trace elements and identify their oxidation states in synthetic corundum. A total of 15 corundum samples in red, blue, and yellow, synthesized by melt growth process, were first investigated by X-ray diffraction (XRD) analysis to determine the composition. Electron probe micro-analyzer (EPMA) was used to identify the types of trace elements. Results confirm that all synthetic corundums contain crystalline Al₂O₃ and a wide variety type of trace element, particularly Cr, Fe, and Ti. In red, yellow, and blue corundums respectively. To further determine their oxidation states, synchrotron X-ray absorption near edge structure spectrometry (XANES) was used to observe absorbing energy of each element. XANES results show that red synthetic corundum has Cr³⁺ as a major trace element (62%). The pre-edge absorption energy of Cr³⁺ is at 6001 eV. In addition, Fe²⁺ and Fe³⁺ are dominant oxidation states of yellow synthetic corundum while Ti³⁺and Ti⁴⁺ are dominant oxidation states of blue synthetic corundum. the average absorption energy of Fe and Ti is 4980 eV and 7113 eV respectively. The presence of Fe²⁺, Fe³⁺, Cr³⁺, Ti³⁺, and Ti⁴⁺ in synthetic corundums in this study is governed by comparison absorption energy edge with standard transition. The results of oxidation states in this study conform with natural corundum. However yellow synthetic corundums show difference oxidation state of trace element compared with synthetic in electron spin resonance spectrometer method which found that Ni³⁺ is a dominant oxidation state.Keywords: corundum, trace element, oxidation state, XANES technique
Procedia PDF Downloads 17222 The Correlation Between Self-Talk and COVID-19
Authors: Abigail Vallance
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Current research shows a correlation between declining mental health in the United States and the effect of COVID-19 on young adults and adolescents. Anxiety and depression are the two most common psychiatric illnesses, which are also the leading impediments to academic success. Spending six hours a day or more using computers is associated with higher risks of depression, with this time constraint pervasive even in present-day academia. Along with many hours on the computer, common issues COVID-19 had on students’ academic performance during online school included technical difficulties, poor support services, and difficulty adapting to online learning. Given the volume of requirements with unrealistic deadlines, and despite experiencing COVID-19, students showed an increase in their levels of anxiety. Besides the prevalent effect of COVID-19 on mental health, many studies show a correlation between mental health, COVID-19, academia, and sports performance. Academic research showed that negative self-talk, in relation to one’s self-efficacy, correlated with negative academic performance. Research showed that students who reported negative self-efficacy when test-taking led to negative test results. Furthermore, in sports performance, negative effects were found when athletes engage in negative self-talk. Overall, motivational self-talk, by oneself and through teammates and coaches, correlated with better performance than regular self-talk in sports. In relation to sports performance, the COVID-19 pandemic canceled complete sports seasons for millions of adolescents across the country. Many student-athletes use their sport to release emotions and escape from their mental health, but this was taken away. The purpose of this study is to address the current increase in mental health diagnoses in adolescents, including suicide rates after the COVID-19 pandemic began in 2020.This literature analysis is actively being studied.Keywords: self-talk, COVID-19, mental health, adolescents
Procedia PDF Downloads 5621 Functional Connectivity Signatures of Polygenic Depression Risk in Youth
Authors: Louise Moles, Steve Riley, Sarah D. Lichenstein, Marzieh Babaeianjelodar, Robert Kohler, Annie Cheng, Corey Horien Abigail Greene, Wenjing Luo, Jonathan Ahern, Bohan Xu, Yize Zhao, Chun Chieh Fan, R. Todd Constable, Sarah W. Yip
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Background: Risks for depression are myriad and include both genetic and brain-based factors. However, relationships between these systems are poorly understood, limiting understanding of disease etiology, particularly at the developmental level. Methods: We use a data-driven machine learning approach connectome-based predictive modeling (CPM) to identify functional connectivity signatures associated with polygenic risk scores for depression (DEP-PRS) among youth from the Adolescent Brain and Cognitive Development (ABCD) study across diverse brain states, i.e., during resting state, during affective working memory, during response inhibition, during reward processing. Results: Using 10-fold cross-validation with 100 iterations and permutation testing, CPM identified connectivity signatures of DEP-PRS across all examined brain states (rho’s=0.20-0.27, p’s<.001). Across brain states, DEP-PRS was positively predicted by increased connectivity between frontoparietal and salience networks, increased motor-sensory network connectivity, decreased salience to subcortical connectivity, and decreased subcortical to motor-sensory connectivity. Subsampling analyses demonstrated that model accuracies were robust across random subsamples of N’s=1,000, N’s=500, and N’s=250 but became unstable at N’s=100. Conclusions: These data, for the first time, identify neural networks of polygenic depression risk in a large sample of youth before the onset of significant clinical impairment. Identified networks may be considered potential treatment targets or vulnerability markers for depression risk.Keywords: genetics, functional connectivity, pre-adolescents, depression
Procedia PDF Downloads 6020 Humans, Social Robots, and Mutual Love: An Application of Aristotle’s Nicomachean Ethics
Authors: Ruby Jean Hornsby
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In our rapidly advancing techno-moral world, human-robot relationships are increasingly becoming a part of intimate human life. Indeed, social robots - that is, autonomous or semi-autonomous embodied artificial agents that generally possess human or animal-like qualities (such as responding to environmental stimuli, communicating, learning, performing human tasks, and making autonomous decisions) - have been designed to function as human friends. In light of such advances, immediate philosophical scrutiny is imperative in order to examine the extent to which human-robot interactions constitute genuine friendship and therefore contribute towards the good human life. Aristotle's conception of friendship is philosophically illuminating and sufficiently broad in scope to guide such analysis. On his account, it is necessary (though not sufficient) that for a friendship to exist between two agents - A and B - both agents must have a mutual love for one another. Aristotle claims that A loves B if: Condition 1: A desires those apparent good (qua pleasant, useful, or virtuous) properties attributable to B, and Condition 2: A has goodwill (wishes what is best) for B. This paper argues that human-robot interaction can (and does) successfully meet both conditions; as such, it demonstrates that robots and humans can reciprocally love one another. It will argue for this position by first justifying the claim that a human can desire apparent good features attributable to a robot (i.e., by taking them to be pleasant and/or useful) and outlining how it is that a human can wish a robot well in light of that robot's (quasi-) interests. Next, the paper will argue that a robot can (quasi-)desire certain properties that are attributable to a human before elucidating how it is possible for a robot to act in the interests of a human. Accordingly, this paper will conclude that it is already the case that humans can formulate relationships with robots that involve reciprocated love. This is significant because it suggests that social robots are candidates for human friendship and can therefore contribute toward flourishing human futures.Keywords: ancient philosophy, friendship, inter-disciplinary applied ethics, love, social robotics
Procedia PDF Downloads 10119 Challenges Associated with Recruitment of Professional Doctorate Degree Holders into Ghanaian Universities
Authors: Joseph E. Cobbinah, Abigail A. Aryeh-Adjei
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Over the years, entry into the academia in any Ghanaian university requires an advanced research degree, more preferably traditional doctorate (PhD or DPhil). It is however argued that PhD is more research intensive, so since university teaching involves a lot of research, those having traditional doctorate have good research background to teach in a university and are thus recruited as lecturers. However, in the last ten years, a reasonable number of academics enter Ghanaian universities with professional doctorate degrees, which hitherto was considered to be only suitable for industry, because it gives individuals with just basic research skills needed for professional practice, unlike the traditional PhD which is research intensive degree. Currently, there are a reasonable number of professional doctorate degree holders with qualifications like DBA, EdD, PsychD, DPharm, EngD, among others in various departments in many Ghanaian universities. Maybe, because such degree holders also use the title Dr, some university authorities put them at par with their counterparts with traditional doctorate, although some lecturers with PhD seem to look down upon those with traditional doctorate degrees and this has created some tension amongst those academics. This makes their promotions and holding of university academic positions very problematic in some ways. This paper therefore seeks to investigate the types of professional doctorate degree holders working as lecturers in some selected universities in Ghana and the challenges associated with their recruitment, acceptability and proper integration into universities’ teaching and learning. The paper adopted qualitative research methodology. In all, respondents from three state-owned and privately owned universities were involved in the study. Administrators, lecturers, heads of departments and deans of faculty were interviewed to assess the challenges associated with the recruitment of professional doctorate degree holders and any problems they face in the departments they work. It became evident that, although some lecturers enter the academia with professional doctorate degrees, their counterparts seem not to give them the recognition and respect they deserve. Although there is little or no evidence that professional doctorate degree holders are under performing, recruiting professional doctorate degree holders does not only become a challenge, but also their progression into the university’s promotion ladder become very slow compared to their counterparts with traditional PhD degrees.Keywords: professional doctorate, academia, lecturers, Ghanaian universities, orate
Procedia PDF Downloads 31318 Multi Data Management Systems in a Cluster Randomized Trial in Poor Resource Setting: The Pneumococcal Vaccine Schedules Trial
Authors: Abdoullah Nyassi, Golam Sarwar, Sarra Baldeh, Mamadou S. K. Jallow, Bai Lamin Dondeh, Isaac Osei, Grant A. Mackenzie
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A randomized controlled trial is the "gold standard" for evaluating the efficacy of an intervention. Large-scale, cluster-randomized trials are expensive and difficult to conduct, though. To guarantee the validity and generalizability of findings, high-quality, dependable, and accurate data management systems are necessary. Robust data management systems are crucial for optimizing and validating the quality, accuracy, and dependability of trial data. Regarding the difficulties of data gathering in clinical trials in low-resource areas, there is a scarcity of literature on this subject, which may raise concerns. Effective data management systems and implementation goals should be part of trial procedures. Publicizing the creative clinical data management techniques used in clinical trials should boost public confidence in the study's conclusions and encourage further replication. In the ongoing pneumococcal vaccine schedule study in rural Gambia, this report details the development and deployment of multi-data management systems and methodologies. We implemented six different data management, synchronization, and reporting systems using Microsoft Access, RedCap, SQL, Visual Basic, Ruby, and ASP.NET. Additionally, data synchronization tools were developed to integrate data from these systems into the central server for reporting systems. Clinician, lab, and field data validation systems and methodologies are the main topics of this report. Our process development efforts across all domains were driven by the complexity of research project data collected in real-time data, online reporting, data synchronization, and ways for cleaning and verifying data. Consequently, we effectively used multi-data management systems, demonstrating the value of creative approaches in enhancing the consistency, accuracy, and reporting of trial data in a poor resource setting.Keywords: data management, data collection, data cleaning, cluster-randomized trial
Procedia PDF Downloads 2817 Primary Fallopian Tube Carcinoma: A Case Report
Authors: Mary Abigail T. Ty, Mary Jocelyn Yu-Laygo, Jocelyn Z. Mariano
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This is a case of L.S.T., a 61 year old, G6P4 (3124) who presented with a one month history of intermittent, brownish, watery, non foul smelling vaginal discharge. There were no other accompanying symptoms. On rectovaginal examination, a palpable adnexal mass on the left was appreciated, with the lower border measuring 3 cm. The mass was non-tender, had irregular borders and solid areas. On transvaginal sonography, it revealed a left pelvic mass measuring 3 x 4 x 2 cm, with a Sassone score of 9. It had vascularization. The primary consideration was Ovarian Newgrowth, probably malignant in nature. CA-125 results were slightly elevated at 43.2 u/ml (NV: 0-35 u/ml). After intraoperative evaluation, the left fallopian tube was converted into a 9 x 4.5 x 3 cm bulbous cystic mass with solid areas. On cut section, the ampullary portion of the fallopian tube contained necrotic and friable looking tissues. Specimen was sent for frozen section and results revealed adenocarcinoma of the left fallopian tube. Patient subsequently underwent complete surgical staging with unremarkable post-operative course. The Surg Ico pathologic diagnosis was G6P4 (3124) Fallopian tube serous cystadenocarcinoma stage 1. The mean incidence of PFTC is 3.6 per million women yearly. This is associated with a generally low survival rate. The primary diagnosis is very difficult to establish because only 0–10% of patients suffering from PFTC are diagnosed pre-operatively. Symptoms play a very important role in the discovery of this disease, because there will be no presentation to the hospital without symptoms. The most common of which may be vaginal bleeding, abdominal pain, a palpable mass and ascites. A conglomerate of manifestations may be encountered, but not at all times. This is termed hydrops tubae profluens where there is presence of colicky pain with relief from intermittent passage of serosanguinous vaginal discharge. The significance of this report is to emphasize the rarity of the case and how the dilemma in the diagnosis is almost always present despite ancillary procedures.Keywords: fallopian tube carcinoma, prognosis, rare, risk factors
Procedia PDF Downloads 32116 Nursing-Related Barriers to Children’s Pain Management at Selected Hospitals in Ghana: A Descriptive Qualitative Study
Authors: Abigail Kusi Amponsah, Evans Frimpong Kyei, John Bright Agyemang, Hanson Boakye, Joana Kyei-Dompim, Collins Kwadwo Ahoto, Evans Oduro
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Staff shortages, deficient knowledge, inappropriate attitudes, demanding workloads, analgesic shortages, and low prioritization of pain management have been identified in earlier studies as the nursing-related barriers to optimal children’s pain management. These studies have mainly been undertaken in developed countries, which have different healthcare dynamics than those in developing countries. The current study, therefore, sought to identify and understand the nursing-related barriers to children’s pain management in the Ghanaian context. A descriptive qualitative study was conducted among 28 purposively sampled nurses working in the pediatric units of five hospitals in the Ashanti region of Ghana. Over the course of three months, participants were interviewed on the barriers which prevented them from optimally managing children’s pain in practice. Recorded interviews were transcribed verbatim and deductively analysed based on a conceptual interest in pain assessment and management-related barriers. NVivo 12 plus software guided data management and analyses. The mean age of participating nurses was 30 years, with majority being females (n =24). Participants had worked in the nursing profession for an average of five years and in the pediatric care settings for an average of two years. The nursing-related barriers identified in the present study included communication difficulties in assessing and evaluating pain management interventions with children who have nonfunctional speech, insufficient training, misconceptions on the experience of pain in children, lack of assessment tools, and insufficient number of nurses to manage the workload and nurses’ inability to prescribe analgesics. The present study revealed some barriers which prevented Ghanaian nurses from optimally managing children’s pain. Nurses should be educated, empowered, and supported with the requisite material resources to effectively manage children’s pain and improve outcomes for families, healthcare systems, and the nation. Future studies should explore the facilitators and barriers from other stakeholders involved in pediatric pain managementKeywords: Nursing-Related Barriers, Children, Pain Management, Ghana
Procedia PDF Downloads 18715 Towards Competence-Based Regulatory Sciences Education in Sub-Saharan Africa: Identification of Competencies
Authors: Abigail Ekeigwe, Bethany McGowan, Loran C. Parker, Stephen Byrn, Kari L. Clase
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There are growing calls in the literature to develop and implement competency-based regulatory sciences education (CBRSE) in sub-Saharan Africa to expand and create a pipeline of a competent workforce of regulatory scientists. A defined competence framework is an essential component in developing competency-based education. However, such a competence framework is not available for regulatory scientists in sub-Saharan Africa. The purpose of this research is to identify entry-level competencies for inclusion in a competency framework for regulatory scientists in sub-Saharan Africa as a first step in developing CBRSE. The team systematically reviewed the literature following the PRISMA guidelines for systematic reviews and based on a pre-registered protocol on Open Science Framework (OSF). The protocol has the search strategy and the inclusion and exclusion criteria for publications. All included publications were coded to identify entry-level competencies for regulatory scientists. The team deductively coded the publications included in the study using the 'framework synthesis' model for systematic literature review. The World Health Organization’s conceptualization of competence guided the review and thematic synthesis. Topic and thematic codings were done using NVivo 12™ software. Based on the search strategy in the protocol, 2345 publications were retrieved. Twenty-two (n=22) of the retrieved publications met all the inclusion criteria for the research. Topic and thematic coding of the publications yielded three main domains of competence: knowledge, skills, and enabling behaviors. The knowledge domain has three sub-domains: administrative, regulatory governance/framework, and scientific knowledge. The skills domain has two sub-domains: functional and technical skills. Identification of competencies is the primal step that serves as a bedrock for curriculum development and competency-based education. The competencies identified in this research will help policymakers, educators, institutions, and international development partners design and implement competence-based regulatory science education in sub-Saharan Africa, ultimately leading to access to safe, quality, and effective medical products.Keywords: competence-based regulatory science education, competencies, systematic review, sub-Saharan Africa
Procedia PDF Downloads 19714 Virtual Academy Next: Addressing Transition Challenges Through a Gamified Virtual Transition Program for Students with Disabilities
Authors: Jennifer Gallup, Joel Bocanegra, Greg Callan, Abigail Vaughn
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Students with disabilities (SWD) engaged in a distance summer program delivered over multiple virtual mediums that used gaming principles to teach and practice self-regulated learning (SRL) through the process of exploring possible jobs. Gaming quests were developed to explore jobs and teach transition skills. Students completed specially designed quests that taught and reinforced SRL and problem-solving through individual, group, and teacher-led experiences. SRL skills learned were reinforced through guided job explorations over the context of MinecraftEDU, zoom with experts in the career, collaborations with a team over Marco Polo, and Zoom. The quests were developed and laid out on an accessible web page, with active learning opportunities and feedback conducted within multiple virtual mediums including MinecraftEDU. Gaming mediums actively engage players in role-playing, problem-solving, critical thinking, and collaboration. Gaming has been used as a medium for education since the inception of formal education. Games, and specifically board games, are pre-historic, meaning we had board games before we had written language. Today, games are widely used in education, often as a reinforcer for behavior or for rewards for work completion. Games are not often used as a direct method of instruction and assessment; however, the inclusion of games as an assessment tool and as a form of instruction increases student engagement and participation. Games naturally include collaboration, problem-solving, and communication. Therefore, our summer program was developed using gaming principles and MinecraftEDU. This manuscript describes a virtual learning summer program called Virtual Academy New and Exciting Transitions (VAN) that was redesigned from a face-to-face setting to a completely online setting with a focus on SWD aged 14-21. The focus of VAN was to address transition planning needs such as problem-solving skills, self-regulation, interviewing, job exploration, and communication for transition-aged youth diagnosed with various disabilities (e.g., learning disabilities, attention-deficit hyperactivity disorder, intellectual disability, down syndrome, autism spectrum disorder).Keywords: autism, disabilities, transition, summer program, gaming, simulations
Procedia PDF Downloads 7513 Detecting Elderly Abuse in US Nursing Homes Using Machine Learning and Text Analytics
Authors: Minh Huynh, Aaron Heuser, Luke Patterson, Chris Zhang, Mason Miller, Daniel Wang, Sandeep Shetty, Mike Trinh, Abigail Miller, Adaeze Enekwechi, Tenille Daniels, Lu Huynh
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Machine learning and text analytics have been used to analyze child abuse, cyberbullying, domestic abuse and domestic violence, and hate speech. However, to the authors’ knowledge, no research to date has used these methods to study elder abuse in nursing homes or skilled nursing facilities from field inspection reports. We used machine learning and text analytics methods to analyze 356,000 inspection reports, which have been extracted from CMS Form-2567 field inspections of US nursing homes and skilled nursing facilities between 2016 and 2021. Our algorithm detected occurrences of the various types of abuse, including physical abuse, psychological abuse, verbal abuse, sexual abuse, and passive and active neglect. For example, to detect physical abuse, our algorithms search for combinations or phrases and words suggesting willful infliction of damage (hitting, pinching or burning, tethering, tying), or consciously ignoring an emergency. To detect occurrences of elder neglect, our algorithm looks for combinations or phrases and words suggesting both passive neglect (neglecting vital needs, allowing malnutrition and dehydration, allowing decubiti, deprivation of information, limitation of freedom, negligence toward safety precautions) and active neglect (intimidation and name-calling, tying the victim up to prevent falls without consent, consciously ignoring an emergency, not calling a physician in spite of indication, stopping important treatments, failure to provide essential care, deprivation of nourishment, leaving a person alone for an inappropriate amount of time, excessive demands in a situation of care). We further compare the prevalence of abuse before and after Covid-19 related restrictions on nursing home visits. We also identified the facilities with the most number of cases of abuse with no abuse facilities within a 25-mile radius as most likely candidates for additional inspections. We also built an interactive display to visualize the location of these facilities.Keywords: machine learning, text analytics, elder abuse, elder neglect, nursing home abuse
Procedia PDF Downloads 14812 Identification, Synthesis, and Biological Evaluation of the Major Human Metabolite of NLRP3 Inflammasome Inhibitor MCC950
Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson
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MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3
Procedia PDF Downloads 25211 The Relationship between Violence against Women in the Family and Common Mental Disorders in Urban Informal Settlements of Mumbai, India: A Cross-Sectional Study
Authors: Abigail Bentley, Audrey Prost, Nayreen Daruwalla, Apoorwa Gupta, David Osrin
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BACKGROUND: Intimate partner violence (IPV) can impact a woman’s physical, reproductive and mental health, including common mental disorders such as anxiety and depression. However, people other than an intimate partner may also perpetrate violence against women in the family, particularly in India. This study aims to investigate the relationship between experiences of violence perpetrated by the husband and other members of the wider household and symptoms of common mental disorders in women residing in informal settlement (slum) areas of Mumbai. METHODS: Experiences of violence were assessed through a detailed cross-sectional survey of 598 women, including questions about specific acts of emotional, economic, physical and sexual violence across different time points in the woman’s life and the main perpetrator of each act. Symptoms of common mental disorders were assessed using the 12-item General Health Questionnaire (GHQ-12). The GHQ-12 scores were divided into four groups and the relationship between experiences of each type of violence in the last 12 months and GHQ-12 score group was analyzed using ordinal logistic regression, adjusted for the woman’s age and clustering. RESULTS: 482 (81%) women consented to interview. On average, they were 28.5 years old, had completed 7 years of education and had been married 9 years. 88% were Muslim and 47% lived in joint and 53% in nuclear families. 44% of women had experienced at least one act of violence in their lifetime (33% emotional, 22% economic, 23% physical, 12% sexual). 7% had a high GHQ-12 score (6 or above). For violence experiences in the last 12 months, the odds of being in the highest GHQ-12 score group versus the lower groups combined were 13.1 for emotional violence, 6.5 for economic, 5.7 for physical and 6.3 for sexual (p<0.001 for all outcomes). DISCUSSION: The high level of violence reported across the lifetime could be due to the detailed assessment of violent acts at multiple time points and the inclusion of perpetrators within the family other than the husband. Each type of violence was associated with greater odds of a higher GHQ-12 score and therefore more symptoms of common mental disorders. Emotional violence was far more strongly associated with symptoms of common mental disorders than physical or sexual violence. However, it is not possible to attribute causal directionality to the association. Further work to investigate the relationship between differing severity of violence experiences and women’s mental health and the components of emotional violence that make it so strongly associated with symptoms of common mental disorders would be beneficial.Keywords: common mental disorders, family violence, India, informal settlements, mental health, violence against women
Procedia PDF Downloads 36010 A Comparison of qCON/qNOX to the Bispectral Index as Indices of Antinociception in Surgical Patients Undergoing General Anesthesia with Laryngeal Mask Airway
Authors: Roya Yumul, Ofelia Loani Elvir-Lazo, Sevan Komshian, Ruby Wang, Jun Tang
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BACKGROUND: An objective means for monitoring the anti-nociceptive effects of perioperative medications has long been desired as a way to provide anesthesiologists information regarding a patient’s level of antinociception and preclude any untoward autonomic responses and reflexive muscular movements from painful stimuli intraoperatively. To this end, electroencephalogram (EEG) based tools including BIS and qCON were designed to provide information about the depth of sedation while qNOX was produced to inform on the degree of antinociception. The goal of this study was to compare the reliability of qCON/qNOX to BIS as specific indicators of response to nociceptive stimulation. METHODS: Sixty-two patients undergoing general anesthesia with LMA were included in this study. Institutional Review Board (IRB) approval was obtained, and informed consent was acquired prior to patient enrollment. Inclusion criteria included American Society of Anesthesiologists (ASA) class I-III, 18 to 80 years of age, and either gender. Exclusion criteria included the inability to consent. Withdrawal criteria included conversion to the endotracheal tube and EEG malfunction. BIS and qCON/qNOX electrodes were simultaneously placed on all patients prior to induction of anesthesia and were monitored throughout the case, along with other perioperative data, including patient response to noxious stimuli. All intraoperative decisions were made by the primary anesthesiologist without influence from qCON/qNOX. Student’s t-distribution, prediction probability (PK), and ANOVA were used to statistically compare the relative ability to detect nociceptive stimuli for each index. Twenty patients were included for the preliminary analysis. RESULTS: A comparison of overall intraoperative BIS, qCON and qNOX indices demonstrated no significant difference between the three measures (N=62, p> 0.05). Meanwhile, index values for qNOX (62±18) were significantly higher than those for BIS (46±14) and qCON (54±19) immediately preceding patient responses to nociceptive stimulation in a preliminary analysis (N=20, * p= 0.0408). Notably, certain hemodynamic measurements demonstrated a significant increase in response to painful stimuli (MAP increased from 74 ±13 mm Hg at baseline to 84 ± 18 mm Hg during noxious stimuli [p= 0.032] and HR from 76 ± 12 BPM at baseline to 80 ± 13 BPM during noxious stimuli [p=0.078] respectively). CONCLUSION: In this observational study, BIS and qCON/qNOX provided comparable information on patients’ level of sedation throughout the course of an anesthetic. Meanwhile, increases in qNOX values demonstrated a superior correlation to an imminent response to stimulation relative to all other indicesKeywords: antinociception, BIS, general anesthesia, LMA, qCON/qNOX
Procedia PDF Downloads 1379 The Effect of Technology on Skin Development and Progress
Authors: Haidy Weliam Megaly Gouda
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Dermatology is often a neglected specialty in low-resource settings despite the high morbidity associated with skin disease. This becomes even more significant when associated with HIV infection, as dermatological conditions are more common and aggressive in HIV-positive patients. African countries have the highest HIV infection rates, and skin conditions are frequently misdiagnosed and mismanaged because of a lack of dermatological training and educational material. The frequent lack of diagnostic tests in the African setting renders basic clinical skills all the more vital. This project aimed to improve the diagnosis and treatment of skin disease in the HIV population in a district hospital in Malawi. A basic dermatological clinical tool was developed and produced in collaboration with local staff and based on available literature and data collected from clinics. The aim was to improve diagnostic accuracy and provide guidance for the treatment of skin disease in HIV-positive patients. A literature search within Embassy, Medline and Google Scholar was performed and supplemented through data obtained from attending 5 Antiretroviral clinics. From the literature, conditions were selected for inclusion in the resource if they were described as specific, more prevalent, or extensive in the HIV population or have more adverse outcomes if they develop in HIV patients. Resource-appropriate treatment options were decided using Malawian Ministry of Health guidelines and textbooks specific to African dermatology. After the collection of data and discussion with local clinical and pharmacy staff, a list of 15 skin conditions was included, and a booklet was created using the simple layout of a picture, a diagnostic description of the disease and treatment options. Clinical photographs were collected from local clinics (with full consent of the patient) or from the book ‘Common Skin Diseases in Africa’ (permission granted if fully acknowledged and used in a not-for-profit capacity). This tool was evaluated by the local staff alongside an educational teaching session on skin disease. This project aimed to reduce uncertainty in diagnosis and provide guidance for appropriate treatment in HIV patients by gathering information into one practical and manageable resource. To further this project, we hope to review the effectiveness of the tool in practice.Keywords: prevalence and pattern of skin diseases, impact on quality of life, rural Nepal, interventions, quality switched ruby laser, skin color river blindness, clinical signs, circularity index, grey level run length matrix, grey level co-occurrence matrix, local binary pattern, object detection, ring detection, shape identification
Procedia PDF Downloads 648 The Attitudes of Senior High School Students Toward Work Immersion Programs of Nazareth School of National University
Authors: Kim Katherine Castillo, Nelson John Datubatang, Terrence Phillip Dy, Norelie Hampac, Reichen Crismark Martinez, Nina Faith Pantinople, Jose Dante Santos II, Marchel Ann Santos, Sophia Abigail Santiago, Zyrill Xsar San Juan, Aira Mae Tagao, Crystal Kylla Viagedor
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The Work Immersion Program was implemented to help students gain abundant work-related experiences while on-site; additionally, the program aims to help students improve their competencies and interpersonal skills as they are given the option to join the workforce if they ever choose to do so after senior high school. The work immersion experience posed diverse challenges for students, spanning personal, financial, engagement, environmental, and equipment-related domains. These included the need for assistance in time management, transportation expenses, and procurement of materials. Furthermore, students faced difficulties in independent task completion and encountered suboptimal work environments. Addressing these multifaceted obstacles is crucial to optimize the educational outcomes of work immersion programs. In addition to the challenges, several other issues have been identified, including the absence of standardized work immersion programs across schools and industries, the challenges in securing appropriate work immersion placements, the necessity for enhanced monitoring and evaluation of program effectiveness, and the limited availability of field programs aligned with students' chosen courses. Furthermore, there is a lack of comprehensive information regarding the attitudes of Senior High School students toward work immersion programs within their respective schools. This study aims to investigate the attitudes of senior high school students at Nazareth School of National University towards work immersion programs, with a focus on identifying factors that influence their perception and participation, including collegiality and expectations. By exploring the students' attitudes, the research endeavors to enhance the school's work immersion programs and contribute to the overall educational experience of the students. This study addresses challenges related to work immersion programs, focusing on six subtopics: Work Immersion, Work Immersion in the Philippines, Students' Attitudes, Factors Affecting Students' Attitudes, Effectiveness of Work Immersion for Senior High School Students, and Students' Perception and Willingness to Participate. Using a descriptive research design, the study examines the attitudes of senior high school students at Nazareth School of National University in Manila. Data was collected from 100 students, representing different academic strands, through a 35-item researcher-made survey. Descriptive statistics, including measures of central tendency and variability, will be used to analyze the data using JASP, providing valuable insights into the students' attitudes toward work immersion.Keywords: attitudes, challenges, educational outcomes, work immersion programs
Procedia PDF Downloads 967 C-Spine Imaging in a Non-trauma Centre: Compliance with NEXUS Criteria Audit
Authors: Andrew White, Abigail Lowe, Kory Watkins, Hamed Akhlaghi, Nicole Winter
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The timing and appropriateness of diagnostic imaging are critical to the evaluation and management of traumatic injuries. Within the subclass of trauma patients, the prevalence of c-spine injury is less than 4%. However, the incidence of delayed diagnosis within this cohort has been documented as up to 20%, with inadequate radiological examination most cited issue. In order to assess those in which c-spine injury cannot be fully excluded based on clinical examination alone and, therefore, should undergo diagnostic imaging, a set of criteria is used to provide clinical guidance. The NEXUS (National Emergency X-Radiography Utilisation Study) criteria is a validated clinical decision-making tool used to facilitate selective c-spine radiography. The criteria allow clinicians to determine whether cervical spine imaging can be safely avoided in appropriate patients. The NEXUS criteria are widely used within the Emergency Department setting given their ease of use and relatively straightforward application and are used in the Victorian State Trauma System’s guidelines. This audit utilized retrospective data collection to examine the concordance of c-spine imaging in trauma patients to that of the NEXUS criteria and assess compliance with state guidance on diagnostic imaging in trauma. Of the 183 patients that presented with trauma to the head, neck, or face (244 excluded due to incorrect triage), 98 did not undergo imaging of the c-spine. Out of those 98, 44% fulfilled at least one of the NEXUS criteria, meaning the c-spine could not be clinically cleared as per the current guidelines. The criterion most met was intoxication, comprising 42% (18 of 43), with midline spinal tenderness (or absence of documentation of this) the second most common with 23% (10 of 43). Intoxication being the most met criteria is significant but not unexpected given the cohort of patients seen at St Vincent’s and within many emergency departments in general. Given these patients will always meet NEXUS criteria, an element of clinical judgment is likely needed, or concurrent use of the Canadian C-Spine Rules to exclude the need for imaging. Midline tenderness as a met criterion was often in the context of poor or absent documentation relating to this, emphasizing the importance of clear and accurate assessments. The distracting injury was identified in 7 out of the 43 patients; however, only one of these patients exhibited a thoracic injury (T11 compression fracture), with the remainder comprising injuries to the extremities – some studies suggest that C-spine imaging may not be required in the evaluable blunt trauma patient despite distracting injuries in any body regions that do not involve the upper chest. This emphasises the need for standardised definitions for distracting injury, at least at a departmental/regional level. The data highlights the currently poor application of the NEXUS guidelines, with likely common themes throughout emergency departments, highlighting the need for further education regarding implementation and potential refinement/clarification of criteria. Of note, there appeared to be no significant differences between levels of experience with respect to inappropriately clearing the c-spine clinically with respect to the guidelines.Keywords: imaging, guidelines, emergency medicine, audit
Procedia PDF Downloads 726 Monitoring the Responses to Nociceptive Stimuli During General Anesthesia Based on Electroencephalographic Signals in Surgical Patients Undergoing General Anesthesia with Laryngeal Mask Airway (LMA)
Authors: Ofelia Loani Elvir Lazo, Roya Yumul, Sevan Komshian, Ruby Wang, Jun Tang
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Background: Monitoring the anti-nociceptive drug effect is useful because a sudden and strong nociceptive stimulus may result in untoward autonomic responses and muscular reflex movements. Monitoring the anti-nociceptive effects of perioperative medications has long been desiredas a way to provide anesthesiologists information regarding a patient’s level of antinociception and preclude any untoward autonomic responses and reflexive muscular movements from painful stimuli intraoperatively.To this end, electroencephalogram (EEG) based tools includingBIS and qCON were designed to provide information about the depth of sedation whileqNOXwas produced to informon the degree of antinociception.The goal of this study was to compare the reliability of qCON/qNOX to BIS asspecific indicators of response to nociceptive stimulation. Methods: Sixty-two patients undergoing general anesthesia with LMA were included in this study. Institutional Review Board(IRB) approval was obtained, and informed consent was acquired prior to patient enrollment. Inclusion criteria included American Society of Anesthesiologists (ASA) class I-III, 18 to 80 years of age, and either gender. Exclusion criteria included the inability to consent. Withdrawal criteria included conversion to endotracheal tube and EEG malfunction. BIS and qCON/qNOX electrodes were simultaneously placed o62n all patientsprior to induction of anesthesia and were monitored throughout the case, along with other perioperative data, including patient response to noxious stimuli. All intraoperative decisions were made by the primary anesthesiologist without influence from qCON/qNOX. Student’s t-distribution, prediction probability (PK), and ANOVA were used to statistically compare the relative ability to detect nociceptive stimuli for each index. Twenty patients were included for the preliminary analysis. Results: A comparison of overall intraoperative BIS, qCON and qNOX indices demonstrated no significant difference between the three measures (N=62, p> 0.05). Meanwhile, index values for qNOX (62±18) were significantly higher than those for BIS (46±14) and qCON (54±19) immediately preceding patient responses to nociceptive stimulation in a preliminary analysis (N=20, * p= 0.0408). Notably, certain hemodynamic measurements demonstrated a significant increase in response to painful stimuli (MAP increased from74±13 mm Hg at baseline to 84± 18 mm Hg during noxious stimuli [p= 0.032] and HR from 76±12 BPM at baseline to 80±13BPM during noxious stimuli[p=0.078] respectively). Conclusion: In this observational study, BIS and qCON/qNOX provided comparable information on patients’ level of sedation throughout the course of an anesthetic. Meanwhile, increases in qNOX values demonstrated a superior correlation to an imminent response to stimulation relative to all other indices.Keywords: antinociception, bispectral index (BIS), general anesthesia, laryngeal mask airway, qCON/qNOX
Procedia PDF Downloads 925 Hydrogen Purity: Developing Low-Level Sulphur Speciation Measurement Capability
Authors: Sam Bartlett, Thomas Bacquart, Arul Murugan, Abigail Morris
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Fuel cell electric vehicles provide the potential to decarbonise road transport, create new economic opportunities, diversify national energy supply, and significantly reduce the environmental impacts of road transport. A potential issue, however, is that the catalyst used at the fuel cell cathode is susceptible to degradation by impurities, especially sulphur-containing compounds. A recent European Directive (2014/94/EU) stipulates that, from November 2017, all hydrogen provided to fuel cell vehicles in Europe must comply with the hydrogen purity specifications listed in ISO 14687-2; this includes reactive and toxic chemicals such as ammonia and total sulphur-containing compounds. This requirement poses great analytical challenges due to the instability of some of these compounds in calibration gas standards at relatively low amount fractions and the difficulty associated with undertaking measurements of groups of compounds rather than individual compounds. Without the available reference materials and analytical infrastructure, hydrogen refuelling stations will not be able to demonstrate compliance to the ISO 14687 specifications. The hydrogen purity laboratory at NPL provides world leading, accredited purity measurements to allow hydrogen refuelling stations to evidence compliance to ISO 14687. Utilising state-of-the-art methods that have been developed by NPL’s hydrogen purity laboratory, including a novel method for measuring total sulphur compounds at 4 nmol/mol and a hydrogen impurity enrichment device, we provide the capabilities necessary to achieve these goals. An overview of these capabilities will be given in this paper. As part of the EMPIR Hydrogen co-normative project ‘Metrology for sustainable hydrogen energy applications’, NPL are developing a validated analytical methodology for the measurement of speciated sulphur-containing compounds in hydrogen at low amount fractions pmol/mol to nmol/mol) to allow identification and measurement of individual sulphur-containing impurities in real samples of hydrogen (opposed to a ‘total sulphur’ measurement). This is achieved by producing a suite of stable gravimetrically-prepared primary reference gas standards containing low amount fractions of sulphur-containing compounds (hydrogen sulphide, carbonyl sulphide, carbon disulphide, 2-methyl-2-propanethiol and tetrahydrothiophene have been selected for use in this study) to be used in conjunction with novel dynamic dilution facilities to enable generation of pmol/mol to nmol/mol level gas mixtures (a dynamic method is required as compounds at these levels would be unstable in gas cylinder mixtures). Method development and optimisation are performed using gas chromatographic techniques assisted by cryo-trapping technologies and coupled with sulphur chemiluminescence detection to allow improved qualitative and quantitative analyses of sulphur-containing impurities in hydrogen. The paper will review the state-of-the art gas standard preparation techniques, including the use and testing of dynamic dilution technologies for reactive chemical components in hydrogen. Method development will also be presented highlighting the advances in the measurement of speciated sulphur compounds in hydrogen at low amount fractions.Keywords: gas chromatography, hydrogen purity, ISO 14687, sulphur chemiluminescence detector
Procedia PDF Downloads 2264 Performance of a Lytic Bacteriophage Cocktail against Pseudomonas aeruginosa in Conditions That Simulate the Cystic Fibrosis Lung Environment
Authors: Isaac Martin, Abigail Lark, Sandra Morales, Eric W. Alton, Jane C. Davies
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Objectives: The cystic fibrosis (CF) lung is a unique microbiological niche, wherein harmful bacteria persist for many years despite antibiotic therapy. Pseudomonas aeruginosa (Pa), the major culprit leading to lung decline and increased mortality, thrives in the lungs of patients with CF due to several factors that have been linked with poor antibiotic performance. Our group is investigating alternative therapies including bacteriophage cocktails with which we have previously demonstrated efficacy against planktonic organisms. In this study, we explored the effects of a 4-phage cocktail on Pa grown in two different conditions, intended to mirror the CF lung: a) alongside standard antibiotic treatment in pre-formed biofilms (structures formed by Pa-secreted exopolysaccharides which provide both physical and cell division barriers to antimicrobials and host defenses and b) in an acidic environment postulated to be present in the CF airway due both to the primary defect in bicarbonate secretion and secondary effects of inflammation. Methods: 16 Pa strains from CF patients at the Royal Brompton Hospital were selected based on sensitivity to a) ceftazidime/ tobramycin and b) the phage cocktail in a conventional plaque assay. To assess efficacy of phage in biofilms, 96 well plates with Pa (5x10⁷ CFU/ ml) were incubated in static conditions, allowing adherent bacterial colonies to form for 24 hr. Ceftazidime and tobramycin (both at 2 × MIC) were added, +/- bacteriophage (4x10⁸ PFU/mL) for a further 24 hr. Cell viability and biomass were estimated using fluorescent resazurin and crystal violet assays, respectively. To evaluate the effect of pH, strains were grown planktonically in shaking 96 well plates at pH 6.0, 6.6, 7.0 and 7.5 with tobramycin or phage, at varying concentrations. Cell viability was quantified by fluorescent resazurin assay. Results: For the biofilm assay, treatment groups were compared with untreated controls and expressed as percent reduction in cell viability and biomass. Addition of the 4-phage cocktail resulted in a 1.3-fold reduction in cell viability and 1.7-fold reduction in biomass (p < 0.001) when compared to standard antibiotic treatment alone. Notably, there was a 50 ± 15% reduction in cell viability and 60 ± 12% reduction in biomass (95% CI) for the 4 biofilms demonstrating the most resistance to antibiotic treatment. 83% of strains tested (n=6) showed decreased bacterial killing by tobramycin at acidic pHs (p < 0.01). However, 25% of strains (n=12) showed improved phage killing at acidic pHs (p < 0.05), with none showing the pattern of reduced efficacy at acidic pH demonstrated by tobramycin. Conclusion: The 4-phage anti-Pa cocktail tested against Pa performs well in pre-formed biofilms and in acidic environments; two conditions intended to mimic the CF lung. To our knowledge, these are the first data looking at the effects of subtle pH changes on phage-mediated bacterial killing in the context of Pa infection. These findings contribute to a growing body of evidence supporting the use of nebulised lytic bacteriophage as a treatment in the context of lung infection.Keywords: biofilm, cystic fibrosis, pH, Pseudomonas aeruginosa, lytic bacteriophage
Procedia PDF Downloads 1763 Culture and Health Equity: Unpacking the Sociocultural Determinants of Eye Health for Indigenous Australian Diabetics
Authors: Aryati Yashadhana, Ted Fields Jnr., Wendy Fernando, Kelvin Brown, Godfrey Blitner, Francis Hayes, Ruby Stanley, Brian Donnelly, Bridgette Jerrard, Anthea Burnett, Anthony B. Zwi
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Indigenous Australians experience some of the worst health outcomes globally, with life expectancy being significantly poorer than those of non-Indigenous Australians. This is largely attributed to preventable diseases such as diabetes (prevalence 39% in Indigenous Australian adults > 55 years), which is attributed to a raised risk of diabetic visual impairment and cataract among Indigenous adults. Our study aims to explore the interface between structural and sociocultural determinants and human agency, in order to understand how they impact (1) accessibility of eye health and chronic disease services and (2) the potential for Indigenous patients to achieve positive clinical eye health outcomes. We used Participatory Action Research methods, and aimed to privilege the voices of Indigenous people through community collaboration. Semi-structured interviews (n=82) and patient focus groups (n=8) were conducted by Indigenous Community-Based Researchers (CBRs) with diabetic Indigenous adults (> 40 years) in four remote communities in Australia. Interviews (n=25) and focus groups (n=4) with primary health care clinicians in each community were also conducted. Data were audio recorded, transcribed verbatim, and analysed thematically using grounded theory, comparative analysis and Nvivo 10. Preliminary analysis occurred in tandem with data collection to determine theoretical saturation. The principal investigator (AY) led analysis sessions with CBRs, fostering cultural and contextual appropriateness to interpreting responses, knowledge exchange and capacity building. Identified themes were conceptualised into three spheres of influence: structural (health services, government), sociocultural (Indigenous cultural values, distrust of the health system, ongoing effects of colonialism and dispossession) and individual (health beliefs/perceptions, patient phenomenology). Permeating these spheres of influence were three core determinants: economic disadvantage, health literacy/education, and cultural marginalisation. These core determinants affected accessibility of services, and the potential for patients to achieve positive clinical outcomes at every level of care (primary, secondary, tertiary). Our findings highlight the clinical realities of institutionalised and structural inequities, illustrated through the lived experiences of Indigenous patients and primary care clinicians in the four sampled communities. The complex determinants surrounding inequity in health for Indigenous Australians, are entrenched through a longstanding experience of cultural discrimination and ostracism. Secure and long term funding of Aboriginal Community Controlled Health Services will be valuable, but are insufficient to address issues of inequity. Rather, working collaboratively with communities to build trust, and identify needs and solutions at the grassroots level, while leveraging community voices to drive change at the systemic/policy level are recommended.Keywords: indigenous, Australia, culture, public health, eye health, diabetes, social determinants of health, sociology, anthropology, health equity, aboriginal and Torres strait islander, primary care
Procedia PDF Downloads 3032 Surface Plasmon Resonance Imaging-Based Epigenetic Assay for Blood DNA Post-Traumatic Stress Disorder Biomarkers
Authors: Judy M. Obliosca, Olivia Vest, Sandra Poulos, Kelsi Smith, Tammy Ferguson, Abigail Powers Lott, Alicia K. Smith, Yang Xu, Christopher K. Tison
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Post-Traumatic Stress Disorder (PTSD) is a mental health problem that people may develop after experiencing traumatic events such as combat, natural disasters, and major emotional challenges. Tragically, the number of military personnel with PTSD correlates directly with the number of veterans who attempt suicide, with the highest rate in the Army. Research has shown epigenetic risks in those who are prone to several psychiatric dysfunctions, particularly PTSD. Once initiated in response to trauma, epigenetic alterations in particular, the DNA methylation in the form of 5-methylcytosine (5mC) alters chromatin structure and represses gene expression. Current methods to detect DNA methylation, such as bisulfite-based genomic sequencing techniques, are laborious and have massive analysis workflow while still having high error rates. A faster and simpler detection method of high sensitivity and precision would be useful in a clinical setting to confirm potential PTSD etiologies, prevent other psychiatric disorders, and improve military health. A nano-enhanced Surface Plasmon Resonance imaging (SPRi)-based assay that simultaneously detects site-specific 5mC base (termed as PTSD base) in methylated genes related to PTSD is being developed. The arrays on a sensing chip were first constructed for parallel detection of PTSD bases using synthetic and genomic DNA (gDNA) samples. For the gDNA sample extracted from the whole blood of a PTSD patient, the sample was first digested using specific restriction enzymes, and fragments were denatured to obtain single-stranded methylated target genes (ssDNA). The resulting mixture of ssDNA was then injected into the assay platform, where targets were captured by specific DNA aptamer probes previously immobilized on the surface of a sensing chip. The PTSD bases in targets were detected by anti-5-methylcytosine antibody (anti-5mC), and the resulting signals were then enhanced by the universal nanoenhancer. Preliminary results showed successful detection of a PTSD base in a gDNA sample. Brighter spot images and higher delta values (control-subtracted reflectivity signal) relative to those of the control were observed. We also implemented the in-house surface activation system for detection and developed SPRi disposable chips. Multiplexed PTSD base detection of target methylated genes in blood DNA from PTSD patients of severity conditions (asymptomatic and severe) was conducted. This diagnostic capability being developed is a platform technology, and upon successful implementation for PTSD, it could be reconfigured for the study of a wide variety of neurological disorders such as traumatic brain injury, Alzheimer’s disease, schizophrenia, and Huntington's disease and can be extended to the analyses of other sample matrices such as urine and saliva.Keywords: epigenetic assay, DNA methylation, PTSD, whole blood, multiplexing
Procedia PDF Downloads 1281 White-Rot Fungi Phellinus as a Source of Antioxidant and Antitumor Agents
Authors: Yogesh Dalvi, Ruby Varghese, Nibu Varghese, C. K. Krishnan Nair
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Introduction: The Genus Phellinus, locally known as Phansomba is a well-known traditional folk medicine. Especially, in Western Ghats of India, many tribes use several species of Phellinus for various ailments related to teeth, throat, tongue, stomach and even wound healing. It is one of the few mushrooms which play a pivotal role in Ayurvedic Dravyaguna. Aim: The present study focuses on to investigate phytochemical analysis, antioxidant, and antitumor (in vitro and in vivo) potential of Phellinus robinae from South India, Kerala Material and Methods: The present study explores the following: 1. Phellinus samples were collected from Ranni, Pathanamthitta district of Kerala state, India from Artocarpus heterophyllus Lam. and species were identified using rDNA region. 2. The fruiting body was shadow dried, powdered and extracted with 50% alcohol using water bath at 60°C which was further condensed by rotary evaporator and lyophilized at minus 40°C temperature. 3. Secondary metabolites were analyzed by using various phytochemical screening assay (Hager’s Test, Wagner’s Test, Sodium hydroxide Test, Lead acetate Test, Ferric chloride Test, Folin-ciocalteu Test, Foaming Test, Benedict’s test, Fehling’s Test and Lowry’s Test). 4. Antioxidant and free radical scavenging activity were analyzed by DPPH, FRAP and Iron chelating assay. 5. The antitumor potential of Water alcohol extract of Phellinus (PAWE) is evaluated through In vitro condition by Trypan blue dye exclusion method in DLA cell line and In vivo by murine model. Result and Discussion: Preliminary phytochemical screening by various biochemical tests revealed presence of a variety of active secondary molecules like alkaloids, flavanoids, saponins, carbohydrate, protein and phenol. In DPPH and FRAP assay PAWE showed significantly higher antioxidant activity as compared to standard Ascorbic acid. While, in Iron chelating assay, PAWE exhibits similar antioxidant activity that of Butylated Hydroxytoluene (BHT) as standard. Further, in the in vitro study, PAWE showed significant inhibition on DLA cell proliferation in dose dependent manner and showed no toxicity on mice splenocytes, when compared to standard chemotherapy drug doxorubicin. In vivo study, oral administration of PAWE showed dose dependent tumor regression in mice and also raised the immunogenicity by restoring levels of antioxidant enzymes in liver and kidney tissue. In both in vitro and in vivo gene expression studies PAWE up-regulates pro-apoptotic genes (Bax, Caspases 3, 8 and 9) and down- regulates anti-apoptotic genes (Bcl2). PAWE also down regulates inflammatory gene (Cox-2) and angiogenic gene (VEGF). Conclusion: Preliminary phytochemical screening revealed that PAWE contains various secondary metabolites which contribute to its antioxidant and free radical scavenging property as evaluated by DPPH, FRAP and Iron chelating assay. PAWE exhibits anti-proliferative activity by the induction of apoptosis through a signaling cascade of death receptor-mediated extrinsic (Caspase8 and Tnf-α), as well as mitochondria-mediated intrinsic (caspase9) and caspase pathways (Caspase3, 8 and 9) and also by regressing angiogenic factor (VEGF) without any inflammation or adverse side effects. Hence, PAWE serve as a potential antioxidant and antitumor agent.Keywords: antioxidant, antitumor, Dalton lymphoma ascites (DLA), fungi, Phellinus robinae
Procedia PDF Downloads 306