5,061 research outputs found
Machine Learning Approaches for the Prioritisation of Cardiovascular Disease Genes Following Genome- wide Association Study
Genome-wide association studies (GWAS) have revealed thousands of genetic loci, establishing itself as a valuable method for unravelling the complex biology of many diseases. As GWAS has grown in size and improved in study design to detect effects, identifying real causal signals, disentangling from other highly correlated markers associated by linkage disequilibrium (LD) remains challenging. This has severely limited GWAS findings and brought the methodâs value into question. Although thousands of disease susceptibility loci have been reported, causal variants and genes at these loci remain elusive. Post-GWAS analysis aims to dissect the heterogeneity of variant and gene signals. In recent years, machine learning (ML) models have been developed for post-GWAS prioritisation. ML models have ranged from using logistic regression to more complex ensemble models such as random forests and gradient boosting, as well as deep learning models (i.e., neural networks). When combined with functional validation, these methods have shown important translational insights, providing a strong evidence-based approach to direct post-GWAS research. However, ML approaches are in their infancy across biological applications, and as they continue to evolve an evaluation of their robustness for GWAS prioritisation is needed. Here, I investigate the landscape of ML across: selected models, input features, bias risk, and output model performance, with a focus on building a prioritisation framework that is applied to blood pressure GWAS results and tested on re-application to blood lipid traits
Study of neural circuits using multielectrode arrays in movement disorders
Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2022-2023. Tutor/Director: RodrĂguez AlluĂŠ, Manuel JosĂŠNeurodegenerative movement-related disorders are characterized by a progressive degeneration and loss of neurons, which lead to motor control impairment. Although the precise mechanisms underlying these conditions are still unknown, an increasing number of studies point towards the analysis of neural networks and functional connectivity to unravel novel insights. The main objective of this work is to understand cellular mechanisms related to dysregulated motor control symptoms in movement disorders, such as Chorea-Acanthocytosis (ChAc), by employing multielectrode arrays to analyze the electrical activity of neuronal networks in mouse models. We found no notable differences in cell viability between neurons with and without VPS13A knockdown, that is the only gene known to be implicated in the disease, suggesting that the absence of VPS13A in neurons may be partially compensated by other proteins. The MEA setup used to capture the electrical activity from neuron primary cultures is described in detail, pointing out its specific characteristics. At last, we present the alternative backup approach implemented to overcome the challenges faced during the research process and to explore the advanced algorithms for signal processing and analysis.
In this report, we present a thorough account of the conception and implementation of our research, outlining the multiple limitations that have been encountered all along the course of the project. We provide a detailed analysis on the projectâs economical and technical feasibility, as well as a comprehensive overview of the ethical and legal aspects considered during the execution
An Exploration of the Suitability of Pharmacy Education in Saudi Arabia to Prepare Graduates to Meet Healthcare Needs: a Mixed-Methods Study
The key role of pharmacists within the health system, particularly in optimising safe, responsible and effective use of medicines, underpins the demand for a highly skilled and competent workforce. Therefore, developing the capacity of pharmacists to attain and maintain essential competencies relevant to the populationâs health needs is required to ensure a high standard of patient care, thereby helping to improve patient and population health. In Saudi Arabia, little evidence exists regarding the assessment of national educational programmesâ structure and outcomes. Moreover, no national competency framework exists for pharmacists in any sector or stage of practice. In the absence of such core quality elements to inform pharmacy education assessment and development, the extent to which pharmacy schools in Saudi Arabia prepare competent pharmacists to address societal needs from pharmacy services is unclear. Therefore, this study aimed to explore the extent to which pharmacy education can prepare competent pharmacists to address the healthcare needs for pharmacy practice in Saudi Arabia.
An exploratory sequential mixed methods research design was used to address the aim of this study in three phases: individual interviews and focus groups were employed with a purposively selected sample of pharmacy policy makers, pharmacists and the public to explore societal healthcare needs and the roles required of pharmacists to meet those needs; a national online survey of pharmacists and an online nominal group consensus method of pharmacy experts were used to identify competencies considered essential to develop a profession-wide national foundation level competency framework; and a case study in which curriculum mapping of two purposively selected Doctor of Pharmacy (PharmD) curricula was used to assess the extent to which the current pharmacy programme in Saudi Arabia meets the identified competencies of the developed national competency framework.
Based on qualitative and quantitative analyses of societal healthcare needs, pharmacistsâ roles, core competencies and curricular contents within the local context of Saudi Arabia, findings showed that there is a mismatch between initial education and real practice needs and expectations. While the countryâs current needs from pharmacists are to optimise health system capacity and increase access to primary care services and medicines expertise in community pharmacies, the study indicated local education is product-oriented with a focus of curricular content and experiential training opportunities in most schools on preparing future pharmacists for hospital pharmacy practice. The study also identified several gaps between current initial education programmes and the competencies required to practise the expected roles, suggesting that current initial education might not prepare the students sufficiently to provide the full range of quality pharmaceutical services as per the countryâs pharmacy practice needs.
The study provided a new understanding of graduatesâ readiness to practise as per the countryâs pharmacy practice needs, the quality of educational programmes and pharmacists' professional development opportunities in Saudi Arabia. Findings maybe used to inform the development of competency-based education and maximise graduatesâ capacity to deliver and develop pharmaceutical services effectively to best meet societal healthcare needs in Saudi Arabia
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Ensuring Access to Safe and Nutritious Food for All Through the Transformation of Food Systems
Annual SHOT Report 2018
SHOT is affiliated to the Royal College of PathologistsAll NHS organisations must move away from a blame culture towards a just and learning culture. All clinical and laboratory staff should be encouraged to become familiar with human factors and ergonomics concepts. All transfusion decisions must be made after carefully assessing the risks and benefits of transfusion therapy. Collaboration and co-ordination among staff is vital
Regulatory Sandboxes and the Public Health
Recently, administrative agencies around the world have engaged in a grand experiment to regulate new technologies: regulatory sandboxes. Regulatory sandboxes allow developers, in cooperation with an agency, to conduct limited tests of new technologies in real-world settings for the pur- pose of generating and sharing information about them. Thus far, however, âregulatory sandboxesââas namedâappear almost exclusively in the con- text of financial technologies, or FinTech. Whether regulatory sandboxes, in fact, exist elsewhere in administrative law would be a significant finding for both regulators and scholars; it would blunt criticisms that agencies are slow to respond to new technologies, provide regulators with an additional tool for governing new technologies, and suggest that lessons learned from current regulatory sandboxes are applicable elsewhere. This Article is the first to explore this broader view of regulatory sand- boxes and develop a synoptic theory of them. To do so, it uses one of the most radical programs to introduce new technologies in U.S. history: the U.S. Food and Drug Administrationâs (âFDAâ)âs Emergency Use Authorization (âEUAâ) program for COVID-19 treatments and vaccines. EUAsâlike regulatory sandboxes but in stark contrast to typical FDA approval processesâfocus on real-world deployment as a means for information gathering. EUAs are also technologically flexible and crafted with close input from the developer, among other features. Generalizing FDAâs experience with EUAs also provides lessons about the intersection of regulatory sandboxes with public trust in the agency, political interference, and the maintenance of regulatory standards. At the same time, FDAâs COVID-19 EUAs are exceptional in two senses: they touch upon the public health, widely considered to be exceptional subject matter in administrative law; and arose in the context of an unprecedented global pandemic. Nonetheless, FDAâs experience with EUAs suggest regulatory sandboxes may be an underexplored and undertheorized feature of administrative governance of new technologies. Future work in the area should assess whether regulatory sandboxes exist under the rubric identified here, which technologies they regulate, and how those sandboxes operate.Ope
In her own words: exploring the subjectivity of Freudâs âteacherâ Anna von Lieben
This project is inspired by Roy Porter (1985), who draws attention to the patient-shaped gap in medical history, and Rita Charon (2006), who emphasises the need to bring the patientâs narrative to the fore in the practice of medicine. The principal aim was to devise a means of accessing the lived experience of a patient who is no longer alive in order to gain an understanding of her narrative. Anna von Lieben was identified as a suitable subject as she wrote a substantial quantity of autopathographical poetry suitable for analysis and her status as Freudâs patient makes her a person of significant interest to the history of medicine.
The poems were analysed using Interpretative Phenomenological Analysis (IPA), an idiographic and inductive method of qualitative research, based on Heideggerian hermeneutic phenomenology, which explores the lived experience of individuals and is committed to understanding the first-person perspective from the third-person position.
The main findings from the IPA study reveal that Anna experienced a prolonged period of malaise, starting in late adolescence which she believed to result, at least partly, from a traumatic experience which occurred at that time. The analysis also indicates that Anna suffered from deep and lasting feelings of guilt and shame. The discovery of additional family documentation enabled me to contextualise and add substance to the findings of the IPA study. Annaâs husbandâs diaries in particular reveal that Anna:
⢠had a severe and longstanding gynaecological disorder
⢠suffered from severe morphinism
⢠did not benefit from Freudâs treatment which seemed neither to ease her symptoms nor identify any cause
⢠was treated in Paris, not by Jean-Martin Charcot as previously supposed, but by a French hydrotherapist, Theodore Keller, who appears to have become a person of considerable significance in her life.
The above findings led me to investigate Annaâs comorbidities (gynaecological disease and morphinism) and to show how those could be responsible for much of the symptomatology identified by Freud as âhysteriaâ. I then explore the possibility that her psychotic-like experiences could have been iatrogenically induced by her treatment first by Keller and then by Freud. Finally, I propose a fourfold set of hypotheses as an alternative to Freudâs diagnosis of hysteria
How to Be a God
When it comes to questions concerning the nature of Reality, Philosophers and Theologians have the answers.
Philosophers have the answers that canât be proven right. Theologians have the answers that canât be proven wrong.
Todayâs designers of Massively-Multiplayer Online Role-Playing Games create realities for a living. They canât spend centuries mulling over the issues: they have to face them head-on. Their practical experiences can indicate which theoretical proposals actually work in practice.
Thatâs todayâs designers. Tomorrowâs will have a whole new set of questions to answer.
The designers of virtual worlds are the literal gods of those realities. Suppose Artificial Intelligence comes through and allows us to create non-player characters as smart as us. What are our responsibilities as gods? How should we, as gods, conduct ourselves?
How should we be gods
Hunting Wildlife in the Tropics and Subtropics
The hunting of wild animals for their meat has been a crucial activity in the evolution of humans. It continues to be an essential source of food and a generator of income for millions of Indigenous and rural communities worldwide. Conservationists rightly fear that excessive hunting of many animal species will cause their demise, as has already happened throughout the Anthropocene. Many species of large mammals and birds have been decimated or annihilated due to overhunting by humans. If such pressures continue, many other species will meet the same fate. Equally, if the use of wildlife resources is to continue by those who depend on it, sustainable practices must be implemented. These communities need to remain or become custodians of the wildlife resources within their lands, for their own well-being as well as for biodiversity in general. This title is also available via Open Access on Cambridge Core
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