Search results for: Willi McFarland
5 Language Development in Rare Diseases: Angelman Syndrome vs Prader-Willi Syndrome
Authors: Sara Canas Pedrosa, Esther Moraleda SepuLveda
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Angelman Syndrome (AS) and Prader-Willi Syndrome (PWS) are considered rare genetic disorders that share the same chromosomal region: 15q11.2-q13. This is why both share some common characteristics, such as, delay in language development. However, there is still little research that specifically focuses on the linguistic profile in these populations. Therefore, the objective of this study was to know the characteristics of oral and written language that Angelman Syndrome and Prader-Willi Syndrome present from the point of view of parents. The sample consisted of 36 families (with children between 6 and 17 years old), of which 23 had children with AS and 13 had children with PWS. All of them answered the Language Assessment Scale of the standardized test CELF-4, Spanish Clinical Evaluation of Language Fundamentals-4 (Wiig, Secord & Semel, 2006). The scale is made up of 40 items that assesses the perception of parents in areas such as: difficulty of listening, speaking, reading and writing. The results indicate that the majority of parents manifest problems in almost all the sub-areas related to oral language and written language, taking into account that many do not achieve a literacy level, with similar results in comparison with both syndromes. These data support the importance of working on oral language delay and its relationship with the subsequent learning of literacy throughout its development.Keywords: Angelman Syndrome , development, language, Prader-Willi Syndrome
Procedia PDF Downloads 1384 The Risk of Hyperglycemia Associated with Use of Dolutegravir among Adults Living with HIV in Kampala, Uganda: A Case Control Study
Authors: Daphine Namara, Jeremy I. Schwartz, Andrew K. Tusubira, Willi McFarland, Caroline Birungi, Fred C. Semitala, Martin Muddu
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Emerging evidence suggests a possible association between hyperglycemia and dolutegravir (DTG), a preferred first-line antiretroviral agent in sub-Saharan Africa (SSA). There is a need for rigorous studies to validate this association in the face of increasing DTG use and the burden of non-communicable diseases among people living with HIV (PLHIV). We conducted a case-control study to assess the risk of hyperglycemia associated with the use of DTG among PLHIV attending Mulago ISS Clinic in Kampala. Cases had hyperglycemia, while controls had no hyperglycemia, as confirmed by fasting plasma glucose and oral glucose tolerance tests. Demographic, laboratory, and clinical data were collected using interviewer-administered questionnaires and medical record abstraction. The analysis compared cases and controls on DTG use prior to diagnosis of hyperglycemia while controlling for potential confounders using multivariable logistic regression. We included 204 cases and 231 controls. In multivariable analysis, patients with prior DTG use had seven times greater odds of subsequent diagnosis of hyperglycemia compared to those who had non-DTG-based regimens (adjusted odds ratio [aOR] 7.01, 95% CI 1.96-25.09). The odds of hyperglycemia also increased with age (56 years and above vs. 18-35, aOR 12.38, 95% CI 3.79-40.50) and hypertension (aOR 5.78, 95% CI 2.53-13.21). Our study demonstrates a strong association between prior DTG exposure and subsequent diagnosis of hyperglycemia. Given the benefits of DTG, wide-scale use, and the growing burden of diabetes mellitus (DM) in SSA, there is a need for systematic screening for hyperglycemia and consideration of alternate regimens for those at risk for DM.Keywords: HIV, hyperglycemia, doluteravir, diabetes
Procedia PDF Downloads 853 Fast Generation of High-Performance Driveshafts: A Digital Approach to Automated Linked Topology and Design Optimization
Authors: Willi Zschiebsch, Alrik Dargel, Sebastian Spitzer, Philipp Johst, Robert Böhm, Niels Modler
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In this article, we investigate an approach that digitally links individual development process steps by using the drive shaft of an aircraft engine as a representative example of a fiber polymer composite. Such high-performance, lightweight composite structures have many adjustable parameters that influence the mechanical properties. Only a combination of optimal parameter values can lead to energy efficient lightweight structures. The development tools required for the Engineering Design Process (EDP) are often isolated solutions, and their compatibility with each other is limited. A digital framework is presented in this study, which allows individual specialised tools to be linked via the generated data in such a way that automated optimization across programs becomes possible. This is demonstrated using the example of linking geometry generation with numerical structural analysis. The proposed digital framework for automated design optimization demonstrates the feasibility of developing a complete digital approach to design optimization. The methodology shows promising potential for achieving optimal solutions in terms of mass, material utilization, eigenfrequency, and deformation under lateral load with less development effort. The development of such a framework is an important step towards promoting a more efficient design approach that can lead to stable and balanced results.Keywords: digital linked process, composite, CFRP, multi-objective, EDP, NSGA-2, NSGA-3, TPE
Procedia PDF Downloads 752 Development and Testing of an Instrument to Measure Beliefs about Cervical Cancer Screening among Women in Botswana
Authors: Ditsapelo M. McFarland
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Background: Despite the availability of the Pap smear services in urban areas in Botswana, most women in such areas do not seem to screen regular for prevention of the cervical cancer disease. Reasons for non-use of the available Pap smear services are not well understood. Beliefs about cancer may influence participation in cancer screening in these women. The purpose of this study was to develop an instrument to measure beliefs about cervical cancer and Pap smear screening among Black women in Botswana, and evaluate the psychometric properties of the instrument. Significance: Instruments that are designed to measure beliefs about cervical cancer and screening among black women in Botswana, as well as in the surrounding region, are presently not available. Valid and reliable instruments are needed for exploration of the women’s beliefs about cervical cancer. Conceptual Framework: The Health Belief Model (HBM) provided a conceptual framework for the study. Methodology: The study was done in four phases: Phase 1: item generation: 15 items were generated from literature review and qualitative data for each of four conceptually defined HBM constructs: Perceived susceptibility, severity, benefits, and barriers (Version 1). Phase 2: content validity: Four experts who were advanced practice nurses of African descent and were familiar with the content and the HBM evaluated the content. Experts rated the items on a 4-point Likert scale ranging from: 1=not relevant, 2=somewhat relevant, 3=relevant and 4=very relevant. Fifty-five items were retained for instrument development: perceived susceptibility - 11, severity - 14, benefits - 15 and barriers - 15, all measuring on a 4-point Likert scale ranging from strongly disagree (1) to strongly agree (4). (Version 2). Phase 3: pilot testing: The instrument was pilot tested on a convenient sample of 30 women in Botswana and revised as needed. Phase 4: reliability: the revised instrument (Version 3) was submitted to a larger sample of women in Botswana (n=300) for reliability testing. The sample included women who were Batswana by birth and decent, were aged 30 years and above and could complete an English questionnaire. Data were collected with the assistance of trained research assistants. Major findings: confirmatory factor analysis of the 55 items found that a number of items did not adequately load in a four-factor solution. Items that exhibited reasonable reliability and had low frequency of missing values (n=36) were retained: perceived barriers (14 items), perceived benefits (8 items), perceived severity (4 items), and perceived susceptibility (10 items). confirmatory factor analysis (principle components) for a four factor solution using varimax rotation demonstrated that these four factors explained 43% of the variation in these 36 items. Conclusion: reliability analysis using Cronbach’s Alpha gave generally satisfactory results with values from 0.53 to 0.89.Keywords: cervical cancer, factor analysis, psychometric evaluation, varimax rotation
Procedia PDF Downloads 1251 Phorbol 12-Myristate 13-Acetate (PMA)-Differentiated THP-1 Monocytes as a Validated Microglial-Like Model in Vitro
Authors: Amelia J. McFarland, Andrew K. Davey, Shailendra Anoopkumar-Dukie
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Microglia are the resident macrophage population of the central nervous system (CNS), contributing to both innate and adaptive immune response, and brain homeostasis. Activation of microglia occurs in response to a multitude of pathogenic stimuli in their microenvironment; this induces morphological and functional changes, resulting in a state of acute neuroinflammation which facilitates injury resolution. Adequate microglial function is essential for the health of the neuroparenchyma, with microglial dysfunction implicated in numerous CNS pathologies. Given the critical role that these macrophage-derived cells play in CNS homeostasis, there is a high demand for microglial models suitable for use in neuroscience research. The isolation of primary human microglia, however, is both difficult and costly, with microglial activation an unwanted but inevitable result of the extraction process. Consequently, there is a need for the development of alternative experimental models which exhibit morphological, biochemical and functional characteristics of human microglia without the difficulties associated with primary cell lines. In this study, our aim was to evaluate whether THP-1 human peripheral blood monocytes would display microglial-like qualities following an induced differentiation, and, therefore, be suitable for use as surrogate microglia. To achieve this aim, THP-1 human peripheral blood monocytes from acute monocytic leukaemia were differentiated with a range of phorbol 12-myristate 13-acetate (PMA) concentrations (50-200 nM) using two different protocols: a 5-day continuous PMA exposure or a 3-day continuous PMA exposure followed by a 5-day rest in normal media. In each protocol and at each PMA concentration, microglial-like cell morphology was assessed through crystal violet staining and the presence of CD-14 microglial / macrophage cell surface marker. Lipopolysaccharide (LPS) from Escherichia coli (055: B5) was then added at a range of concentrations from 0-10 mcg/mL to activate the PMA-differentiated THP-1 cells. Functional microglial-like behavior was evaluated by quantifying the release of prostaglandin (PG)-E2 and pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α using mediator-specific ELISAs. Furthermore, production of global reactive oxygen species (ROS) and nitric oxide (NO) were determined fluorometrically using dichlorodihydrofluorescein diacetate (DCFH-DA) and diaminofluorescein diacetate (DAF-2-DA) respectively. Following PMA-treatment, it was observed both differentiation protocols resulted in cells displaying distinct microglial morphology from 10 nM PMA. Activation of differentiated cells using LPS significantly augmented IL-1β, TNF-α and PGE2 release at all LPS concentrations under both differentiation protocols. Similarly, a significant increase in DCFH-DA and DAF-2-DA fluorescence was observed, indicative of increases in ROS and NO production. For all endpoints, the 5-day continuous PMA treatment protocol yielded significantly higher mediator levels than the 3-day treatment and 5-day rest protocol. Our data, therefore, suggests that the differentiation of THP-1 human monocyte cells with PMA yields a homogenous microglial-like population which, following stimulation with LPS, undergo activation to release a range of pro-inflammatory mediators associated with microglial activation. Thus, the use of PMA-differentiated THP-1 cells represents a suitable microglial model for in vitro research.Keywords: differentiation, lipopolysaccharide, microglia, monocyte, neuroscience, THP-1
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