2,464 research outputs found

    Quasi-Bernoulli Stick-breaking: Infinite Mixture with Cluster Consistency

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    In mixture modeling and clustering application, the number of components is often not known. The stick-breaking model is an appealing construction that assumes infinitely many components, while shrinking most of the redundant weights to near zero. However, it has been discovered that such a shrinkage is unsatisfactory: even when the component distribution is correctly specified, small and spurious weights will appear and give an inconsistent estimate on the cluster number. In this article, we propose a simple solution that gains stronger control on the redundant weights -- when breaking each stick into two pieces, we adjust the length of the second piece by multiplying it to a quasi-Bernoulli random variable, supported at one and a positive constant close to zero. This substantially increases the chance of shrinking {\em all} the redundant weights to almost zero, leading to a consistent estimator on the cluster number; at the same time, it avoids the singularity due to assigning an exactly zero weight, and maintains a support in the infinite-dimensional space. As a stick-breaking model, its posterior computation can be carried out efficiently via the classic blocked Gibbs sampler, allowing straightforward extension of using non-Gaussian components. Compared to existing methods, our model demonstrates much superior performances in the simulations and data application, showing a substantial reduction in the number of clusters.Comment: 21 pages, 7 figure

    Evaluation of Cancer Metabolomics Using ex vivo High Resolution Magic Angle Spinning (HRMAS) Magnetic Resonance Spectroscopy (MRS)

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    According to World Health Organization (WHO) estimates, cancer is responsible for more deaths than all coronary heart disease or stroke worldwide, serving as a major public health threat around the world. High resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS) has demonstrated its usefulness in the identification of cancer metabolic markers with the potential to improve diagnosis and prognosis for the oncology clinic, due partially to its ability to preserve tissue architecture for subsequent histological and molecular pathology analysis. Capable of the quantification of individual metabolites, ratios of metabolites, and entire metabolomic profiles, HRMAS MRS is one of the major techniques now used in cancer metabolomic research. This article reviews and discusses literature reports of HRMAS MRS studies of cancer metabolomics published between 2010 and 2015 according to anatomical origins, including brain, breast, prostate, lung, gastrointestinal, and neuroendocrine cancers. These studies focused on improving diagnosis and understanding patient prognostication, monitoring treatment effects, as well as correlating with the use of in vivo MRS in cancer clinics

    A statistical learning framework for mapping indirect measurements of ergodic systems to emergent properties

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    The discovery of novel experimental techniques often lags behind contemporary theoretical understanding. In particular, it can be difficult to establish appropriate measurement protocols without analytic descriptions of the underlying system-of-interest. Here we propose a statistical learning framework that avoids the need for such descriptions for ergodic systems. We validate this framework by using Monte Carlo simulation and deep neural networks to learn a mapping between low-field nuclear magnetic resonance spectra and proton exchange rates in ethanol-water mixtures. We found that trained networks exhibited normalized-root-mean-square errors of less than 1% for exchange rates under 150 s-1 but performed poorly for rates above this range. This differential performance occurred because low-field measurements are indistinguishable from one another at fast exchange. Nonetheless, where a discoverable relationship between indirect measurements and emergent dynamics exists, we demonstrate the possibility of approximating it without the need for precise analytic descriptions, allowing experimental science to flourish in the midst of ongoing theoretical wor

    Multi-stakeholder perspectives regarding preferred modalities for mental health intervention delivered in the orthopedic clinic: A qualitative analysis

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    BACKGROUND: Although depressive and anxious symptoms negatively impact musculoskeletal health and orthopedic outcomes, a gap remains in identifying modalities through which mental health intervention can realistically be delivered during orthopedic care. The purpose of this study was to understand orthopedic stakeholders\u27 perceptions regarding the feasibility, acceptability, and usability of digital, printed, and in-person intervention modalities to address mental health as part of orthopedic care. METHODS: This single-center, qualitative study was conducted within a tertiary care orthopedic department. Semi-structured interviews were conducted between January and May 2022. Two stakeholder groups were interviewed using a purposive sampling approach until thematic saturation was reached. The first group included adult orthopedic patients who presented for management of ≥ 3 months of neck or back pain. The second group included early, mid, and late career orthopedic clinicians and support staff members. Stakeholders\u27 interview responses were analyzed using deductive and inductive coding approaches followed by thematic analysis. Patients also performed usability testing of one digital and one printed mental health intervention. RESULTS: Patients included 30 adults out of 85 approached (mean (SD) age 59 [14] years, 21 (70%) women, 12 (40%) non-White). Clinical team stakeholders included 22 orthopedic clinicians and support staff members out of 25 approached (11 (50%) women, 6 (27%) non-White). Clinical team members perceived a digital mental health intervention to be feasible and scalable to implement, and many patients appreciated that the digital modality offered privacy, immediate access to resources, and the ability to engage during non-business hours. However, stakeholders also expressed that a printed mental health resource is still necessary to meet the needs of patients who prefer and/or can only engage with tangible, rather than digital, mental health resources. Many clinical team members expressed skepticism regarding the current feasibility of scalably incorporating in-person support from a mental health specialist into orthopedic care. CONCLUSIONS: Although digital intervention offers implementation-related advantages over printed and in-person mental health interventions, a subset of often underserved patients will not currently be reached using exclusively digital intervention. Future research should work to identify combinations of effective mental health interventions that provide equitable access for orthopedic patients. TRIAL REGISTRATION: Not applicable

    Validation of frequency and mode extraction calculations from time-domain simulations of accelerator cavities

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    The recently developed frequency extraction algorithm [G.R. Werner and J.R. Cary, J. Comp. Phys. 227, 5200 (2008)] that enables a simple FDTD algorithm to be transformed into an efficient eigenmode solver is applied to a realistic accelerator cavity modeled with embedded boundaries and Richardson extrapolation. Previously, the frequency extraction method was shown to be capable of distinguishing M degenerate modes by running M different simulations and to permit mode extraction with minimal post-processing effort that only requires solving a small eigenvalue problem. Realistic calculations for an accelerator cavity are presented in this work to establish the validity of the method for realistic modeling scenarios and to illustrate the complexities of the computational validation process. The method is found to be able to extract the frequencies with error that is less than a part in 10^5. The corrected experimental and computed values differ by about one parts in 10^$, which is accounted for (in largest part) by machining errors. The extraction of frequencies and modes from accelerator cavities provides engineers and physicists an understanding of potential cavity performance as it depends on shape without incurring manufacture and measurement costs

    NMR and Metabolomics—A Roadmap for the Future

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    Metabolomics investigates global metabolic alterations associated with chemical, biological, physiological, or pathological processes. These metabolic changes are measured with various analytical platforms including liquid chromatography-mass spectrometry (LC-MS), gas chromatographymass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR). While LC-MS methods are becoming increasingly popular in the field of metabolomics (accounting for more than 70% of published metabolomics studies to date), there are considerable benefits and advantages to NMR-based methods for metabolomic studies. In fact, according to PubMed, more than 926 papers on NMR-based metabolomics were published in 2021—the most ever published in a given year. This suggests that NMR-based metabolomics continues to grow and has plenty to offer to the scientific community. This perspective outlines the growing applications of NMR in metabolomics, highlights several recent advances in NMR technologies for metabolomics, and provides a roadmap for future advancements

    Image analysis reveals molecularly distinct patterns of TILs in NSCLC associated with treatment outcome.

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    Despite known histological, biological, and clinical differences between lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), relatively little is known about the spatial differences in their corresponding immune contextures. Our study of over 1000 LUAD and LUSC tumors revealed that computationally derived patterns of tumor-infiltrating lymphocytes (TILs) on H&E images were different between LUAD (N = 421) and LUSC (N = 438), with TIL density being prognostic of overall survival in LUAD and spatial arrangement being more prognostically relevant in LUSC. In addition, the LUAD-specific TIL signature was associated with OS in an external validation set of 100 NSCLC treated with more than six different neoadjuvant chemotherapy regimens, and predictive of response to therapy in the clinical trial CA209-057 (n = 303). In LUAD, the prognostic TIL signature was primarily comprised of CD4+ T and CD8+ T cells, whereas in LUSC, the immune patterns were comprised of CD4+ T, CD8+ T, and CD20+ B cells. In both subtypes, prognostic TIL features were associated with transcriptomics-derived immune scores and biological pathways implicated in immune recognition, response, and evasion. Our results suggest the need for histologic subtype-specific TIL-based models for stratifying survival risk and predicting response to therapy. Our findings suggest that predictive models for response to therapy will need to account for the unique morphologic and molecular immune patterns as a function of histologic subtype of NSCLC

    Artificial Intelligence in Supply Chain Operations Planning: Collaboration and Digital Perspectives

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    [EN] Digital transformation provide supply chains (SCs) with extensive accurate data that should be combined with analytical techniques to improve their management. Among these techniques Artificial Intelligence (AI) has proved their suitability, memory and ability to manage uncertain and constantly changing information. Despite the fact that a number of AI literature reviews exist, no comprehensive review of reviews for the SC operations planning has yet been conducted. This paper aims to provide a comprehensive review of AI literature reviews in a structured manner to gain insights into their evolution in incorporating new ICTs and collaboration. Results show that hybrization man-machine and collaboration and ethical aspects are understudied.This research has been funded by the project entitled NIOTOME (Ref. RTI2018-102020-B-I00) (MCI/AEI/FEDER, UE). 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    The Genetic Risk for COVID-19 Severity Is Associated With Defective Immune Responses

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    Recent genome-wide association studies (GWASs) of COVID-19 patients of European ancestry have identified genetic loci significantly associated with disease severity. Here, we employed the detailed clinical, immunological and multi-omics dataset of the Human Functional Genomics Project (HFGP) to explore the physiological significance of the host genetic variants that influence susceptibility to severe COVID-19. A genomics investigation intersected with functional characterization of individuals with high genetic risk for severe COVID-19 susceptibility identified several major patterns: i. a large impact of genetically determined innate immune responses in COVID-19, with ii. increased susceptibility for severe disease in individuals with defective cytokine production; iii. genetic susceptibility related to ABO blood groups is probably mediated through the von Willebrand factor (VWF) and endothelial dysfunction. We further validated these identified associations at transcript and protein levels by using independent disease cohorts. These insights allow a physiological understanding of genetic susceptibility to severe COVID-19, and indicate pathways that could be targeted for prevention and therapy
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