41 research outputs found

    A Model of Function-Based Representations

    Get PDF
    The need to model and to reason about design alternatives throughout the design process demands robust representation schemes of function, behavior, and structure. Function describes the physical effect imposed on an energy or material flow by a design entity without regard for the working principles or physical solutions used to accomplish this effect. Behaviors are the physical events associated with a physical artifact (or hypothesized concept) over time (or simulated time) as perceived by an observer. Structure, the most tangible concept, partitions an artifact into meaningful constituents such as features, Wirk elements, and interfaces in addition to the widely used assemblies and components. The focus of this work is on defining a model for function-based representations that can be used across various design methodologies and for a variety of design tasks throughout all stages of the design process. In particular, the mapping between function and structure is explored and, to a lesser extent, its impact on behavior is noted. Clearly, the issues of a function-based representation\u27s composition and mappings directly impact certain computational synthesis methods that rely on (digitally) archived product design knowledge. Moreover, functions have already been related to not only form, but also information of user actions, performance parameters in the form of equations, and failure mode data. It is essential to understand the composition and mappings of functions and their relation to design activities because this information is part of the foundation for function-based methods, and consequently dictates the performance of those methods. Toward this end, the important findings of this work include a formalism for two aspects of function-based representations (composition and mappings), the supported design activities of the model for function-based representations, and examples of how computational design methods benefit from this formalism

    Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

    Get PDF
    Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

    Get PDF
    IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

    An Interactive Morphological Matrix Computational Design Tool: A Hybrid of Two Methods

    No full text
    This paper builds on previous concept generation techniques explored at the University of Missouri - Rolla and presents an interactive concept generation tool aimed specifically at the early concept generation phase of the design process. Research into automated concept generation design theories led to the creation of two distinct design tools: an automated morphological search that presents a designer with a static matrix of solutions that solve the desired input functionality and a computational concept generation algorithm that presents a designer with a static list of compatible component chains that solve the desired input functionality. The merger of both the automated morphological matrix and concept generation algorithm yields an interactive concept generator that allows the user to select specific solution components while receiving instantaneous feedback on component compatibility. The research presented evaluates the conceptual results from the hybrid morphological matrix approach and compares interactively constructed solutions to those returned by the non-interactive automated morphological matrix generator using a dog food sample packet counter as a case study

    Enhancing Virtual Product Representations for Advanced Design Repository Systems

    No full text
    This paper describes the transformation of an existing set of heterogeneous product knowledge into a coherent design repository that supports product design knowledge archival and web-based search, display, and design model and tool generation. Guided by design theory, existing product information was analyzed and compared against desired outputs to ascertain what information management structure was needed to produce design resources pertinent to the design process. Several test products were catalogued to determine what information was essential without being redundant in representation. This set allowed for the creation of a novel single point of entry application for product information and the development of a relational database for design knowledge archival. Web services were then implemented to support design knowledge retrieval through search, browse, and real-time design tool generation. Further explored in this paper are the fundamental enabling technologies of the design repository system. Additionally, repository-generated design tools are scrutinized alongside human-generated design tools for validation. Through this process researchers have been able to improve the way in which artifact data are gathered, archived, distributed and used
    corecore