Beyond Volume: The Impact of Complex Healthcare Data on the Machine Learning Pipeline

From medical charts to national census, healthcare has traditionally operated under a paper-based paradigm. However, the past decade has marked a long and arduous transformation bringing healthcare into the digital age. Ranging from electronic health records, to digitized imaging and laboratory reports, to public health datasets, today, healthcare now generates an incredible amount of digital information. Such a wealth of data presents an exciting opportunity for integrated machine learning solutions to address problems across multiple facets of healthcare practice and administration. Unfortunately, the ability to derive accurate and informative insights requires more than the ability to execute machine learning models. Rather, a deeper understanding of the data on which the models are run is imperative for their success. While a significant effort has been undertaken to develop models able to process the volume of data obtained during the analysis of millions of digitalized patient records, it is important to remember that volume represents only one aspect of the data. In fact, drawing on data from an increasingly diverse set of sources, healthcare data presents an incredibly complex set of attributes that must be accounted for throughout the machine learning pipeline. This chapter focuses on highlighting such challenges, and is broken down into three distinct components, each representing a phase of the pipeline. We begin with attributes of the data accounted for during preprocessing, then move to considerations during model building, and end with challenges to the interpretation of model output. For each component, we present a discussion around data as it relates to the healthcare domain and offer insight into the challenges each may impose on the efficiency of machine learning techniques.Comment: Healthcare Informatics, Machine Learning, Knowledge Discovery: 20 Pages, 1 Figur

Quantifying Absolute Neutralization Titers against SARS-CoV-2 by a Standardized Virus Neutralization Assay Allows for CrossCohort Comparisons of COVID-19 Sera

The global coronavirus disease 2019 (COVID-19) pandemic has mobilized efforts to develop vaccines and antibody-based therapeutics, including convalescent-phase plasma therapy, that inhibit viral entry by inducing or transferring neutralizing antibodies (nAbs) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (CoV2-S). However, rigorous efficacy testing requires extensive screening with live virus under onerous biosafety level 3 (BSL3) conditions, which limits high-throughput screening of patient and vaccine sera. Myriad BSL2-compatible surrogate virus neutralization assays (VNAs) have been developed to overcome this barrier. Yet, there is marked variability between VNAs and how their results are presented, making intergroup comparisons difficult. To address these limitations, we developed a standardized VNA using CoV2-S pseudotyped particles (CoV2pp) based on vesicular stomatitis virus bearing the Renilla luciferase gene in place of its G glyco-protein (VSVDG); this assay can be robustly produced at scale and generate accurate neutralizing titers within 18 h postinfection. Our standardized CoV2pp VNA showed a strong positive correlation with CoV2-S enzyme-linked immunosorbent assay (ELISA) results and live-virus neutralizations in confirmed convalescent-patient sera. Three independent groups subsequently validated our standardized CoV2pp VNA (n . 120). Our data (i) show that absolute 50% inhibitory concentration (absIC50), absIC80, and absIC90 values can be legitimately compared across diverse cohorts, (ii) highlight the substantial but consistent variability in neutralization potency across these cohorts, and (iii) support the use of the absIC80 as a more meaningful metric for assessing the neutralization potency of a vaccine or convalescent-phase sera. Lastly, we used our CoV2pp in a screen to identify ultrapermissive 293T clones that stably express ACE2 or ACE2 plus TMPRSS2. When these are used in combination with our CoV2pp, we can produce CoV2pp sufficient for 150,000 standardized VNAs/week. IMPORTANCE Vaccines and antibody-based therapeutics like convalescent-phase plasma therapy are premised upon inducing or transferring neutralizing antibodies that inhibit SARS-CoV-2 entry into cells. Virus neutralization assays (VNAs) for measuring neutralizing antibody titers (NATs) are an essential part of determining vaccine or therapeutic efficacy. However, such efficacy testing is limited by the inherent dangers of working with the live virus, which requires specialized high-level biocontainment facilities. We there-fore developed a standardized replication-defective pseudotyped particle system that mimics the entry of live SARS-CoV-2. This tool allows for the safe and efficient measurement of NATs, determination of other forms of entry inhibition, and thorough investigation of virus entry mechanisms. Four independent labs across the globe validated our standardized VNA using diverse cohorts. We argue that a standardized and scalable assay is necessary for meaningful comparisons of the myriad of vaccines and antibody-based therapeutics becoming available. Our data provide generalizable metrics for assessing their efficacy.Fil: Oguntuyo, Kasopefoluwa. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Stevens, Christian S.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Hung, Chuan Tien. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Ikegame, Satoshi. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Acklin, Joshua A.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Kowdle, Shreyas S.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Carmichael, Jillian C.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Chiu, Hsin Ping. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Azarm, Kristopher D.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Haas, Griffin D.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Amanat, Fatima. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Klingler, Jéromine. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Baine, Ian. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Arinsburg, Suzanne. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Bandres, Juan C.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Siddiquey, Mohammed N. A.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Schilke, Robert M.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Woolard, Matthew D.. State University of Louisiana; Estados UnidosFil: Zhang, Hongbo. State University of Louisiana; Estados UnidosFil: Duty, Andrew J.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Kraus, Thomas A.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Moran, Thomas M.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Tortorella, Domenico. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Lim, Jean K.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Hioe, Catarina E.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Zolla Pazner, Susan. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Ivanov, Stanimir S.. State University of Louisiana; Estados UnidosFil: Kamil, Jeremy. State University of Louisiana; Estados UnidosFil: Krammer, Florian. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Lee, Benhur. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Ojeda, Diego Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: González López Ledesma, María Mora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Costa Navarro, Guadalupe Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Pallarés, H. M.. No especifíca;Fil: Sanchez, Lautaro Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Perez, P.. No especifíca;Fil: Ostrowsk, M.. No especifíca;Fil: Villordo, S. M.. No especifíca;Fil: Alvarez, D. E.. No especifíca;Fil: Caramelo, J. J.. No especifíca;Fil: Carradori, J.. No especifíca;Fil: Yanovsky, M. J.. No especifíca

Primary Gastric Lymphoma: Clinicopathologic Study of Gastric Ly-phoma Casess and the Treatment Option of Choice

Introduction: Lymphoma may involve the gastrointestinal tract either primarily or as a manifestation of extensively disseminated systemic disease. Stomach being the most frequent site of primary gastroin-testinal lyphoma, followed by the small bowel and colon respectively (1&2&3). For diagnosis of pi-mary small intestinal lymphoma (PSIL), one most satisfies the criteria specified by Dawson and co-workers.(5) Gastric lymphoma is a common presentation of non-Hodgkin’s lymphoma. Controversy reigns about many aspects of its classification and management, especially regarding roles for surgical resection.The aim of this study is evaluation of 5 years survival and methods of treatment of primary gastric lymphoma in a group of Iranian patients. Methods: The authors review the clinical features, staging, pathology, prognosis, and management of 30 patients with an emphasis on the role of chemotherapy, surgical resection and radiotherapy of 71 gastrointestinal lymphoma cases. Results: A total of 30 patients (19 male and 11 female) with a mean age of 51 years and a range of 34 – 68 years were included in the study. The frequency of primary gastric lymphoma in our series was 42% of the total of primary gastrointestinal lymphoma. The overall survival rate was 47.8% at 5 years. Stag-ing usually was completed using noninvasive techniques. Patients with stage I or II disease were treated with Surgery (gastric resection) and chemotherapy showed improved Free Disease Survival (FDS) of 67% at 5 years. The five-year survival for stage I, II, III and IV patients were 87%, 61%, 25%, and 11% respectively, and the five-year survival for low grade and high grade were 91% and 56%, respec-tively. Stage III or IV and inoperable primary gastric lymphoma were treated with chemotherapy and radiotherapy showed improved Free Disease Survival (FDS) of 67% at five years. The five-year sur-vival for stage I, II, III, IV were 87%, 61%, 25% and 11% respectively, and the five year survival for low grade and high grade were 91% and 56% respectively. Conclusion: Early stage disease and high-grade Lymphoma have a better prognosis and patients who have complete surgical removal of primary tumor and chemotherapy

Retail Channel Structure Impact on Strategic Engineering Product Design

We examine, in a strategic setting, the broad issue of how retail channel structures--retail monopoly versus retail duopoly--impact a manufacturer's optimal new product design, both in terms of engineering design specifications as well as manufacturer and retailer profits. Our strategic framework enables manufacturers in specific contexts to anticipate the reactions of the retailers and competitive manufacturers to new designs in terms of the retail and wholesale pricing and to understand how different channel structures and channel strategies (such as an exclusive channel strategy) impact the engineering design of the new product, conditional on consumer preference distributions and competitor product attributes. Based on a simple numerical and a power tool design example, we illustrate how the insight from the framework translates to design guidelines; specifically, understanding which designs are optimal under differing channel structure conditions, and which design variables need precise targeting given their profit sensitivity. This paper was accepted by Christoph Loch, R&D and product development.new product design, engineering design, research and development, retail channels, marketing, game theory, genetic algorithms, latent class models, structural models

Optimization of Injection Molding Operational Conditions

A major goal of the injection molding process is to produce complex parts to a relatively high degree of accuracy. To do this, one must be able to control the warpage that often occurs in injection molded products. We have developed a methodology to minimize product deformation. Pressure and temperature distributions obtained from flow simulation software are used as an indirect measure of the quality of the molded product. Optimization theory is then used to determine the optimal molding conditions to minimize product deformation

A key region of molecular specificity orchestrates unique ephrin-B1 utilization by Cedar virus

The emergent zoonotic henipaviruses, Hendra, and Nipah are responsible for frequent and fatal disease outbreaks in domestic animals and humans. Specificity of henipavirus attachment glycoproteins (G) for highly species-conserved ephrin ligands underpins their broad host range and is associated with systemic and neurological disease pathologies. Here, we demonstrate that Cedar virus (CedV)—a related henipavirus that is ostensibly nonpathogenic—possesses an idiosyncratic entry receptor repertoire that includes the common henipaviral receptor, ephrin-B2, but, distinct from pathogenic henipaviruses, does not include ephrin-B3. Uniquely among known henipaviruses, CedV can use ephrin-B1 for cellular entry. Structural analyses of CedV-G reveal a key region of molecular specificity that directs ephrin-B1 utilization, while preserving a universal mode of ephrin-B2 recognition. The structural and functional insights presented uncover diversity within the known henipavirus receptor repertoire and suggest that only modest structural changes may be required to modulate receptor specificities within this group of lethal human pathogens

Femtosecond laser-induced melting and shaping of indium nanostructures on silicon wafers

We study the modification of indium semi-spherical nanostructures with radii of around 175 nm on silicon wafers into linear microstructures more than 2 mu m long in the direction of polarization of laser pulses (1.56 mu m, 150 fs, up to 7.5 nJ and 30 000 laser pulses with 8 MHz repetition rate). The experimental results and a rudimentary analysis confirm that melting occurs from intense laser pulses. In short, we demonstrate that melting of the indium droplet followed by trapping in high spatial frequency laser induced periodic surface structures on a silicon substrate cause nanostructure modification. The understanding of the modification process, melting, and moving in the nano-grating structured field, pave the way to design nanostructures of arbitrary shapes at the sub-wavelength scale. Published by AIP Publishing.Air Force Office of Scientific Research (AFOSR) [FA9550-15-1-0389]12 month embargo; published online: 17 July 2018This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

B. Besharati Multi-Objective Single Product Robust Optimization: An Integrated Design and Marketing Approach

We present an integrated design and marketing approach to facilitate the generation of an optimal robust set of product design alternatives to carry forward to the prototyping stage. The approach considers variability in both (i