8,087 research outputs found

    Converging organoids and extracellular matrix::New insights into liver cancer biology

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    Graduate Catalog of Studies, 2023-2024

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    Three-dimensional topology-based analysis segments volumetric and spatiotemporal fluorescence microscopy

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    Image analysis techniques provide objective and reproducible statistics for interpreting microscopy data. At higher dimensions, three-dimensional (3D) volumetric and spatiotemporal data highlight additional properties and behaviors beyond the static 2D focal plane. However, increased dimensionality carries increased complexity, and existing techniques for general segmentation of 3D data are either primitive, or highly specialized to specific biological structures. Borrowing from the principles of 2D topological data analysis (TDA), we formulate a 3D segmentation algorithm that implements persistent homology to identify variations in image intensity. From this, we derive two separate variants applicable to spatial and spatiotemporal data, respectively. We demonstrate that this analysis yields both sensitive and specific results on simulated data and can distinguish prominent biological structures in fluorescence microscopy images, regardless of their shape. Furthermore, we highlight the efficacy of temporal TDA in tracking cell lineage and the frequency of cell and organelle replication

    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

    Evaluation Methodologies in Software Protection Research

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    Man-at-the-end (MATE) attackers have full control over the system on which the attacked software runs, and try to break the confidentiality or integrity of assets embedded in the software. Both companies and malware authors want to prevent such attacks. This has driven an arms race between attackers and defenders, resulting in a plethora of different protection and analysis methods. However, it remains difficult to measure the strength of protections because MATE attackers can reach their goals in many different ways and a universally accepted evaluation methodology does not exist. This survey systematically reviews the evaluation methodologies of papers on obfuscation, a major class of protections against MATE attacks. For 572 papers, we collected 113 aspects of their evaluation methodologies, ranging from sample set types and sizes, over sample treatment, to performed measurements. We provide detailed insights into how the academic state of the art evaluates both the protections and analyses thereon. In summary, there is a clear need for better evaluation methodologies. We identify nine challenges for software protection evaluations, which represent threats to the validity, reproducibility, and interpretation of research results in the context of MATE attacks

    Beam scanning by liquid-crystal biasing in a modified SIW structure

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    A fixed-frequency beam-scanning 1D antenna based on Liquid Crystals (LCs) is designed for application in 2D scanning with lateral alignment. The 2D array environment imposes full decoupling of adjacent 1D antennas, which often conflicts with the LC requirement of DC biasing: the proposed design accommodates both. The LC medium is placed inside a Substrate Integrated Waveguide (SIW) modified to work as a Groove Gap Waveguide, with radiating slots etched on the upper broad wall, that radiates as a Leaky-Wave Antenna (LWA). This allows effective application of the DC bias voltage needed for tuning the LCs. At the same time, the RF field remains laterally confined, enabling the possibility to lay several antennas in parallel and achieve 2D beam scanning. The design is validated by simulation employing the actual properties of a commercial LC medium

    Cyber Conflict and Just War Theory

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    Knowledge Distillation and Continual Learning for Optimized Deep Neural Networks

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    Over the past few years, deep learning (DL) has been achieving state-of-theart performance on various human tasks such as speech generation, language translation, image segmentation, and object detection. While traditional machine learning models require hand-crafted features, deep learning algorithms can automatically extract discriminative features and learn complex knowledge from large datasets. This powerful learning ability makes deep learning models attractive to both academia and big corporations. Despite their popularity, deep learning methods still have two main limitations: large memory consumption and catastrophic knowledge forgetting. First, DL algorithms use very deep neural networks (DNNs) with many billion parameters, which have a big model size and a slow inference speed. This restricts the application of DNNs in resource-constraint devices such as mobile phones and autonomous vehicles. Second, DNNs are known to suffer from catastrophic forgetting. When incrementally learning new tasks, the model performance on old tasks significantly drops. The ability to accommodate new knowledge while retaining previously learned knowledge is called continual learning. Since the realworld environments in which the model operates are always evolving, a robust neural network needs to have this continual learning ability for adapting to new changes

    Anwendungen maschinellen Lernens für datengetriebene Prävention auf Populationsebene

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    Healthcare costs are systematically rising, and current therapy-focused healthcare systems are not sustainable in the long run. While disease prevention is a viable instrument for reducing costs and suffering, it requires risk modeling to stratify populations, identify high- risk individuals and enable personalized interventions. In current clinical practice, however, systematic risk stratification is limited: on the one hand, for the vast majority of endpoints, no risk models exist. On the other hand, available models focus on predicting a single disease at a time, rendering predictor collection burdensome. At the same time, the den- sity of individual patient data is constantly increasing. Especially complex data modalities, such as -omics measurements or images, may contain systemic information on future health trajectories relevant for multiple endpoints simultaneously. However, to date, this data is inaccessible for risk modeling as no dedicated methods exist to extract clinically relevant information. This study built on recent advances in machine learning to investigate the ap- plicability of four distinct data modalities not yet leveraged for risk modeling in primary prevention. For each data modality, a neural network-based survival model was developed to extract predictive information, scrutinize performance gains over commonly collected covariates, and pinpoint potential clinical utility. Notably, the developed methodology was able to integrate polygenic risk scores for cardiovascular prevention, outperforming existing approaches and identifying benefiting subpopulations. Investigating NMR metabolomics, the developed methodology allowed the prediction of future disease onset for many common diseases at once, indicating potential applicability as a drop-in replacement for commonly collected covariates. Extending the methodology to phenome-wide risk modeling, elec- tronic health records were found to be a general source of predictive information with high systemic relevance for thousands of endpoints. Assessing retinal fundus photographs, the developed methodology identified diseases where retinal information most impacted health trajectories. In summary, the results demonstrate the capability of neural survival models to integrate complex data modalities for multi-disease risk modeling in primary prevention and illustrate the tremendous potential of machine learning models to disrupt medical practice toward data-driven prevention at population scale.Die Kosten im Gesundheitswesen steigen systematisch und derzeitige therapieorientierte Gesundheitssysteme sind nicht nachhaltig. Angesichts vieler verhinderbarer Krankheiten stellt die Prävention ein veritables Instrument zur Verringerung von Kosten und Leiden dar. Risikostratifizierung ist die grundlegende Voraussetzung für ein präventionszentri- ertes Gesundheitswesen um Personen mit hohem Risiko zu identifizieren und Maßnah- men einzuleiten. Heute ist eine systematische Risikostratifizierung jedoch nur begrenzt möglich, da für die meisten Krankheiten keine Risikomodelle existieren und sich verfüg- bare Modelle auf einzelne Krankheiten beschränken. Weil für deren Berechnung jeweils spezielle Sets an Prädiktoren zu erheben sind werden in Praxis oft nur wenige Modelle angewandt. Gleichzeitig versprechen komplexe Datenmodalitäten, wie Bilder oder -omics- Messungen, systemische Informationen über zukünftige Gesundheitsverläufe, mit poten- tieller Relevanz für viele Endpunkte gleichzeitig. Da es an dedizierten Methoden zur Ex- traktion klinisch relevanter Informationen fehlt, sind diese Daten jedoch für die Risikomod- ellierung unzugänglich, und ihr Potenzial blieb bislang unbewertet. Diese Studie nutzt ma- chinelles Lernen, um die Anwendbarkeit von vier Datenmodalitäten in der Primärpräven- tion zu untersuchen: polygene Risikoscores für die kardiovaskuläre Prävention, NMR Meta- bolomicsdaten, elektronische Gesundheitsakten und Netzhautfundusfotos. Pro Datenmodal- ität wurde ein neuronales Risikomodell entwickelt, um relevante Informationen zu extra- hieren, additive Information gegenüber üblicherweise erfassten Kovariaten zu quantifizieren und den potenziellen klinischen Nutzen der Datenmodalität zu ermitteln. Die entwickelte Me-thodik konnte polygene Risikoscores für die kardiovaskuläre Prävention integrieren. Im Falle der NMR-Metabolomik erschloss die entwickelte Methodik wertvolle Informa- tionen über den zukünftigen Ausbruch von Krankheiten. Unter Einsatz einer phänomen- weiten Risikomodellierung erwiesen sich elektronische Gesundheitsakten als Quelle prädik- tiver Information mit hoher systemischer Relevanz. Bei der Analyse von Fundusfotografien der Netzhaut wurden Krankheiten identifiziert für deren Vorhersage Netzhautinformationen genutzt werden könnten. Zusammengefasst zeigten die Ergebnisse das Potential neuronaler Risikomodelle die medizinische Praxis in Richtung einer datengesteuerten, präventionsori- entierten Medizin zu verändern
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