6,892 research outputs found

    A Multi-level Analysis on Implementation of Low-Cost IVF in Sub-Saharan Africa: A Case Study of Uganda.

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    Introduction: Globally, infertility is a major reproductive disease that affects an estimated 186 million people worldwide. In Sub-Saharan Africa, the burden of infertility is considerably high, affecting one in every four couples of reproductive age. Furthermore, infertility in this context has severe psychosocial, emotional, economic and health consequences. Absence of affordable fertility services in Sub-Saharan Africa has been justified by overpopulation and limited resources, resulting in inequitable access to infertility treatment compared to developed countries. Therefore, low-cost IVF (LCIVF) initiatives have been developed to simplify IVF-related treatment, reduce costs, and improve access to treatment for individuals in low-resource contexts. However, there is a gap between the development of LCIVF initiatives and their implementation in Sub-Saharan Africa. Uganda is the first country in East and Central Africa to undergo implementation of LCIVF initiatives within its public health system at Mulago Women’s Hospital. Methods: This was an exploratory, qualitative, single, case study conducted at Mulago Women’s Hospital in Kampala, Uganda. The objective of this study was to explore how LCIVF initiatives have been implemented within the public health system of Uganda at the macro-, meso- and micro-level. Primary qualitative data was collected using semi-structured interviews, hospital observations informal conversations, and document review. Using purposive and snowball sampling, a total of twenty-three key informants were interviewed including government officials, clinicians (doctors, nurses, technicians), hospital management, implementers, patient advocacy representatives, private sector practitioners, international organizational representatives, educational institution, and professional medical associations. Sources of secondary data included government and non-government reports, hospital records, organizational briefs, and press outputs. Using a multi-level data analysis approach, this study undertook a hybrid inductive/deductive thematic analysis, with the deductive analysis guided by the Consolidated Framework for Implementation Research (CFIR). Findings: Factors facilitating implementation included international recognition of infertility as a reproductive disease, strong political advocacy and oversight, patient needs & advocacy, government funding, inter-organizational collaboration, tension to change, competition in the private sector, intervention adaptability & trialability, relative priority, motivation &advocacy of fertility providers and specialist training. While barriers included scarcity of embryologists, intervention complexity, insufficient knowledge, evidence strength & quality of intervention, inadequate leadership engagement & hospital autonomy, poor public knowledge, limited engagement with traditional, cultural, and religious leaders, lack of salary incentives and concerns of revenue loss associated with low-cost options. Research contributions: This study contributes to knowledge of factors salient to implementation of LCIVF initiatives in a Sub-Saharan context. Effective implementation of these initiatives requires (1) sustained political support and favourable policy & legislation, (2) public sensitization and engagement of traditional, cultural, and religious leaders (3) strengthening local innovation and capacity building of fertility health workers, in particular embryologists (4) sustained implementor leadership engagement and inter-organizational collaboration and (5) proven clinical evidence and utilization of LCIVF initiatives in innovator countries. It also adds to the literature on the applicability of the CFIR framework in explaining factors that influence successful implementation in developing countries and offer opportunities for comparisons across studies

    Using machine learning to predict pathogenicity of genomic variants throughout the human genome

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    Geschätzt mehr als 6.000 Erkrankungen werden durch Veränderungen im Genom verursacht. Ursachen gibt es viele: Eine genomische Variante kann die Translation eines Proteins stoppen, die Genregulation stören oder das Spleißen der mRNA in eine andere Isoform begünstigen. All diese Prozesse müssen überprüft werden, um die zum beschriebenen Phänotyp passende Variante zu ermitteln. Eine Automatisierung dieses Prozesses sind Varianteneffektmodelle. Mittels maschinellem Lernen und Annotationen aus verschiedenen Quellen bewerten diese Modelle genomische Varianten hinsichtlich ihrer Pathogenität. Die Entwicklung eines Varianteneffektmodells erfordert eine Reihe von Schritten: Annotation der Trainingsdaten, Auswahl von Features, Training verschiedener Modelle und Selektion eines Modells. Hier präsentiere ich ein allgemeines Workflow dieses Prozesses. Dieses ermöglicht es den Prozess zu konfigurieren, Modellmerkmale zu bearbeiten, und verschiedene Annotationen zu testen. Der Workflow umfasst außerdem die Optimierung von Hyperparametern, Validierung und letztlich die Anwendung des Modells durch genomweites Berechnen von Varianten-Scores. Der Workflow wird in der Entwicklung von Combined Annotation Dependent Depletion (CADD), einem Varianteneffektmodell zur genomweiten Bewertung von SNVs und InDels, verwendet. Durch Etablierung des ersten Varianteneffektmodells für das humane Referenzgenome GRCh38 demonstriere ich die gewonnenen Möglichkeiten Annotationen aufzugreifen und neue Modelle zu trainieren. Außerdem zeige ich, wie Deep-Learning-Scores als Feature in einem CADD-Modell die Vorhersage von RNA-Spleißing verbessern. Außerdem werden Varianteneffektmodelle aufgrund eines neuen, auf Allelhäufigkeit basierten, Trainingsdatensatz entwickelt. Diese Ergebnisse zeigen, dass der entwickelte Workflow eine skalierbare und flexible Möglichkeit ist, um Varianteneffektmodelle zu entwickeln. Alle entstandenen Scores sind unter cadd.gs.washington.edu und cadd.bihealth.org frei verfügbar.More than 6,000 diseases are estimated to be caused by genomic variants. This can happen in many possible ways: a variant may stop the translation of a protein, interfere with gene regulation, or alter splicing of the transcribed mRNA into an unwanted isoform. It is necessary to investigate all of these processes in order to evaluate which variant may be causal for the deleterious phenotype. A great help in this regard are variant effect scores. Implemented as machine learning classifiers, they integrate annotations from different resources to rank genomic variants in terms of pathogenicity. Developing a variant effect score requires multiple steps: annotation of the training data, feature selection, model training, benchmarking, and finally deployment for the model's application. Here, I present a generalized workflow of this process. It makes it simple to configure how information is converted into model features, enabling the rapid exploration of different annotations. The workflow further implements hyperparameter optimization, model validation and ultimately deployment of a selected model via genome-wide scoring of genomic variants. The workflow is applied to train Combined Annotation Dependent Depletion (CADD), a variant effect model that is scoring SNVs and InDels genome-wide. I show that the workflow can be quickly adapted to novel annotations by porting CADD to the genome reference GRCh38. Further, I demonstrate the integration of deep-neural network scores as features into a new CADD model, improving the annotation of RNA splicing events. Finally, I apply the workflow to train multiple variant effect models from training data that is based on variants selected by allele frequency. In conclusion, the developed workflow presents a flexible and scalable method to train variant effect scores. All software and developed scores are freely available from cadd.gs.washington.edu and cadd.bihealth.org

    Fairness Testing: A Comprehensive Survey and Analysis of Trends

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    Unfair behaviors of Machine Learning (ML) software have garnered increasing attention and concern among software engineers. To tackle this issue, extensive research has been dedicated to conducting fairness testing of ML software, and this paper offers a comprehensive survey of existing studies in this field. We collect 100 papers and organize them based on the testing workflow (i.e., how to test) and testing components (i.e., what to test). Furthermore, we analyze the research focus, trends, and promising directions in the realm of fairness testing. We also identify widely-adopted datasets and open-source tools for fairness testing

    Knowledge-based Modelling of Additive Manufacturing for Sustainability Performance Analysis and Decision Making

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    Additiivista valmistusta on pidetty käyttökelpoisena monimutkaisissa geometrioissa, topologisesti optimoiduissa kappaleissa ja kappaleissa joita on muuten vaikea valmistaa perinteisillä valmistusprosesseilla. Eduista huolimatta, yksi additiivisen valmistuksen vallitsevista haasteista on ollut heikko kyky tuottaa toimivia osia kilpailukykyisillä tuotantomäärillä perinteisen valmistuksen kanssa. Mallintaminen ja simulointi ovat tehokkaita työkaluja, jotka voivat auttaa lyhentämään suunnittelun, rakentamisen ja testauksen sykliä mahdollistamalla erilaisten tuotesuunnitelmien ja prosessiskenaarioiden nopean analyysin. Perinteisten ja edistyneiden valmistusteknologioiden mahdollisuudet ja rajoitukset määrittelevät kuitenkin rajat uusille tuotekehityksille. Siksi on tärkeää, että suunnittelijoilla on käytettävissään menetelmät ja työkalut, joiden avulla he voivat mallintaa ja simuloida tuotteen suorituskykyä ja siihen liittyvän valmistusprosessin suorituskykyä, toimivien korkea arvoisten tuotteiden toteuttamiseksi. Motivaation tämän väitöstutkimuksen tekemiselle on, meneillään oleva kehitystyö uudenlaisen korkean lämpötilan suprajohtavan (high temperature superconducting (HTS)) magneettikokoonpanon kehittämisessä, joka toimii kryogeenisissä lämpötiloissa. Sen monimutkaisuus edellyttää monitieteisen asiantuntemuksen lähentymistä suunnittelun ja prototyyppien valmistuksen aikana. Tutkimus hyödyntää tietopohjaista mallinnusta valmistusprosessin analysoinnin ja päätöksenteon apuna HTS-magneettien mekaanisten komponenttien suunnittelussa. Tämän lisäksi, tutkimus etsii mahdollisuuksia additiivisen valmistuksen toteutettavuuteen HTS-magneettikokoonpanon tuotannossa. Kehitetty lähestymistapa käyttää fysikaalisiin kokeisiin perustuvaa tuote-prosessi-integroitua mallinnusta tuottamaan kvantitatiivista ja laadullista tietoa, joka määrittelee prosessi-rakenne-ominaisuus-suorituskyky-vuorovaikutuksia tietyille materiaali-prosessi-yhdistelmille. Tuloksina saadut vuorovaikutukset integroidaan kaaviopohjaiseen malliin, joka voi auttaa suunnittelutilan tutkimisessa ja täten auttaa varhaisessa suunnittelu- ja valmistuspäätöksenteossa. Tätä varten testikomponentit valmistetaan käyttämällä kahta metallin additiivista valmistus prosessia: lankakaarihitsaus additiivista valmistusta (wire arc additive manufacturing) ja selektiivistä lasersulatusta (selective laser melting). Rakenteellisissa sovelluksissa yleisesti käytetyistä metalliseoksista (ruostumaton teräs, pehmeä teräs, luja niukkaseosteinen teräs, alumiini ja kupariseokset) testataan niiden mekaaniset, lämpö- ja sähköiset ominaisuudet. Lisäksi tehdään metalliseosten mikrorakenteen karakterisointi, jotta voidaan ymmärtää paremmin valmistusprosessin parametrien vaikutusta materiaalin ominaisuuksiin. Integroitu mallinnustapa yhdistää kerätyn kokeellisen tiedon, olemassa olevat analyyttiset ja empiiriset vuorovaikutus suhteet, sekä muut tietopohjaiset mallit (esim. elementtimallit, koneoppimismallit) päätöksenteon tukijärjestelmän muodossa, joka mahdollistaa optimaalisen materiaalin, valmistustekniikan, prosessiparametrien ja muitten ohjausmuuttujien valinnan, lopullisen 3d-tulosteun komponentin halutun rakenteen, ominaisuuksien ja suorituskyvyn saavuttamiseksi. Valmistuspäätöksenteko tapahtuu todennäköisyysmallin, eli Bayesin verkkomallin toteuttamisen kautta, joka on vankka, modulaarinen ja sovellettavissa muihin valmistusjärjestelmiin ja tuotesuunnitelmiin. Väitöstyössä esitetyn mallin kyky parantaa additiivisien valmistusprosessien suorituskykyä ja laatua, täten edistää kestävän tuotannon tavoitteita.Additive manufacturing (AM) has been considered viable for complex geometries, topology optimized parts, and parts that are otherwise difficult to produce using conventional manufacturing processes. Despite the advantages, one of the prevalent challenges in AM has been the poor capability of producing functional parts at production volumes that are competitive with traditional manufacturing. Modelling and simulation are powerful tools that can help shorten the design-build-test cycle by enabling rapid analysis of various product designs and process scenarios. Nevertheless, the capabilities and limitations of traditional and advanced manufacturing technologies do define the bounds for new product development. Thus, it is important that the designers have access to methods and tools that enable them to model and simulate product performance and associated manufacturing process performance to realize functional high value products. The motivation for this dissertation research stems from ongoing development of a novel high temperature superconducting (HTS) magnet assembly, which operates in cryogenic environment. Its complexity requires the convergence of multidisciplinary expertise during design and prototyping. The research applies knowledge-based modelling to aid manufacturing process analysis and decision making in the design of mechanical components of the HTS magnet. Further, it explores the feasibility of using AM in the production of the HTS magnet assembly. The developed approach uses product-process integrated modelling based on physical experiments to generate quantitative and qualitative information that define process-structure-property-performance interactions for given material-process combinations. The resulting interactions are then integrated into a graph-based model that can aid in design space exploration to assist early design and manufacturing decision-making. To do so, test components are fabricated using two metal AM processes: wire and arc additive manufacturing and selective laser melting. Metal alloys (stainless steel, mild steel, high-strength low-alloyed steel, aluminium, and copper alloys) commonly used in structural applications are tested for their mechanical-, thermal-, and electrical properties. In addition, microstructural characterization of the alloys is performed to further understand the impact of manufacturing process parameters on material properties. The integrated modelling approach combines the collected experimental data, existing analytical and empirical relationships, and other data-driven models (e.g., finite element models, machine learning models) in the form of a decision support system that enables optimal selection of material, manufacturing technology, process parameters, and other control variables for attaining desired structure, property, and performance characteristics of the final printed component. The manufacturing decision making is performed through implementation of a probabilistic model i.e., a Bayesian network model, which is robust, modular, and can be adapted for other manufacturing systems and product designs. The ability of the model to improve throughput and quality of additive manufacturing processes will boost sustainable manufacturing goals

    Measurement of the Environmental Impact of Materials

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    Throughout their life cycles—from production, usage, through to disposal—materials and products interact with the environment (water, soil, and air). At the same time, they are exposed to environmental influences and, through their emissions, have an impact on the environment, people, and health. Accelerated experimental testing processes can be used to predict the long-term environmental consequences of innovative products before these actually enter the environment. We are living in a material world. Building materials, geosynthetics, wooden toys, soil, nanomaterials, composites, wastes and more are research subjects examined by the authors of this book. The interactions of materials with the environment are manifold. Therefore, it is important to assess the environmental impact of these interactions. Some answers to how this task can be achieved are given in this Special Issue

    Modelling, Monitoring, Control and Optimization for Complex Industrial Processes

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    This reprint includes 22 research papers and an editorial, collected from the Special Issue "Modelling, Monitoring, Control and Optimization for Complex Industrial Processes", highlighting recent research advances and emerging research directions in complex industrial processes. This reprint aims to promote the research field and benefit the readers from both academic communities and industrial sectors

    An exploration of adherence and persistence in overactive bladder and other long-term conditions

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    Background and aims Overactive bladder is a common, bothersome, and chronic condition associated with symptoms of urinary urgency, incontinence, increased daytime micturition frequency and nocturia. Despite exerting a significant burden on quality of life, adherence, and persistence behaviours with OAB are particularly poor in comparison with other long-term conditions. The aims of the present work were to explore themes relating to medicine-taking behaviours in OAB and other long-term conditions and to suggest ways to improve them. Methods A systematic literature review was undertaken to understand the current landscape of qualitative work exploring adherence and persistence with OAB patients. A qualitative study involving 1:1 semi-structured interviews was conducted with OAB patients to explore the context and drivers for adherence and persistence behaviours using thematic analysis. A comparative analysis was then undertaken with qualitative papers exploring medicinetaking behaviours in a chronic bowel condition, type II diabetes, and multimorbidity to explore the themes identified in the OAB study for convergence and divergence in other conditions and to contextualise the learnings from the former study. Results The systematic literature review revealed a gap in the literature of qualitative exploration of adherence and persistence behaviours in OAB patients. The OAB study found a range of drivers for non-adherent behaviours including a perceived lack of treatment efficacy, side effects, unclear instructions, and drug and condition hierarchies, as well as the rich context within which these themes sit. The comparative analysis study supported the findings of the OAB study demonstrating evidence of key themes transcending across conditions, including a perceived lack of treatment efficacy and side effects, as well as nuances associated with the OAB experience. Conclusions The present work has identified key drivers for non-adherent behaviours in OAB patients and sets out a number of recommendations categorised within the World Health Organisation’s 5 dimensions of adherence. These include addressing the poor understanding and illness perception of OAB by patients and others, by improving the provision and availability of information, as well as the work of patient support groups; scrutiny on the support within primary care to OAB patients before and after diagnosis; and the encouragement of realistic expectations of the condition and treatment with mindful use of prescriber’s language at the point of prescribing. The present work has further highlighted the utility of conceptual models of adherence such as COM-B and the NCF in understanding medicine-taking behaviours in the context of OAB

    Affinity-Based Reinforcement Learning : A New Paradigm for Agent Interpretability

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    The steady increase in complexity of reinforcement learning (RL) algorithms is accompanied by a corresponding increase in opacity that obfuscates insights into their devised strategies. Methods in explainable artificial intelligence seek to mitigate this opacity by either creating transparent algorithms or extracting explanations post hoc. A third category exists that allows the developer to affect what agents learn: constrained RL has been used in safety-critical applications and prohibits agents from visiting certain states; preference-based RL agents have been used in robotics applications and learn state-action preferences instead of traditional reward functions. We propose a new affinity-based RL paradigm in which agents learn strategies that are partially decoupled from reward functions. Unlike entropy regularisation, we regularise the objective function with a distinct action distribution that represents a desired behaviour; we encourage the agent to act according to a prior while learning to maximise rewards. The result is an inherently interpretable agent that solves problems with an intrinsic affinity for certain actions. We demonstrate the utility of our method in a financial application: we learn continuous time-variant compositions of prototypical policies, each interpretable by its action affinities, that are globally interpretable according to customers’ financial personalities. Our method combines advantages from both constrained RL and preferencebased RL: it retains the reward function but generalises the policy to match a defined behaviour, thus avoiding problems such as reward shaping and hacking. Unlike Boolean task composition, our method is a fuzzy superposition of different prototypical strategies to arrive at a more complex, yet interpretable, strategy.publishedVersio

    Corporate Social Responsibility: the institutionalization of ESG

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    Understanding the impact of Corporate Social Responsibility (CSR) on firm performance as it relates to industries reliant on technological innovation is a complex and perpetually evolving challenge. To thoroughly investigate this topic, this dissertation will adopt an economics-based structure to address three primary hypotheses. This structure allows for each hypothesis to essentially be a standalone empirical paper, unified by an overall analysis of the nature of impact that ESG has on firm performance. The first hypothesis explores the evolution of CSR to the modern quantified iteration of ESG has led to the institutionalization and standardization of the CSR concept. The second hypothesis fills gaps in existing literature testing the relationship between firm performance and ESG by finding that the relationship is significantly positive in long-term, strategic metrics (ROA and ROIC) and that there is no correlation in short-term metrics (ROE and ROS). Finally, the third hypothesis states that if a firm has a long-term strategic ESG plan, as proxied by the publication of CSR reports, then it is more resilience to damage from controversies. This is supported by the finding that pro-ESG firms consistently fared better than their counterparts in both financial and ESG performance, even in the event of a controversy. However, firms with consistent reporting are also held to a higher standard than their nonreporting peers, suggesting a higher risk and higher reward dynamic. These findings support the theory of good management, in that long-term strategic planning is both immediately economically beneficial and serves as a means of risk management and social impact mitigation. Overall, this contributes to the literature by fillings gaps in the nature of impact that ESG has on firm performance, particularly from a management perspective
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