A novel platform for isotype-specific testing of autoantibodies.

The objective of this study was to test if a novel platform could be used for isotype-specific autoantibody testing in humans. Further, we evaluated if testing with this novel platform enables earlier detection of insulin autoantibodies in individuals that have first-degree relatives with type-1 diabetes than currently used approaches. Longitudinal serum samples from participants were collected before and after they converted to become positive for insulin autoantibodies by the current standardly used assays. Using a novel plasmonic gold chip platform, we tested these samples for IgM isotype-specific autoantibodies. Serial serum samples from individuals without diabetes were also tested as a comparison control cohort. Our results demonstrate proof-of-concept that a plasmonic gold chip can specifically detect the IgM insulin autoantibody. Five out of the six individuals that converted to being positive for insulin autoantibodies by standard testing had significant IgM autoantibodies on the plasmonic chip platform. The plasmonic chip platform detected IgM autoantibodies earlier than standard testing by up to 4 years. Our results indicate that the plasmonic gold platform can specifically detect the IgM isotype autoantibodies and suggest that combining isotype-specific testing with currently used approaches enables earlier detection of insulin autoantibodies in individuals that have first-degree relatives with type 1 diabetes

An Innovative Approach for Community Engagement: Using an Audience Response System

Community-based participatory research methods allow for community engagement in the effort to reduce cancer health disparities. Community engagement involves health professionals becoming a part of the community in order to build trust, learn from the community and empower them to reduce disparities through their own initiatives and ideas. Audience Response Systems (ARS) are an innovative and engaging way to involve the community and obtain data for research purposes using keypads to report results via power point. The use of ARS within communities is very limited and serves to widen the disparity gap by not delivering new advances in medical knowledge and technology among all population groups. ARS was implemented at a community town hall event sponsored by a National Institute on Minority Health and Health Disparities Exploratory Center of Excellence, the Center for Equal Health. Participants appreciated being able to see how everyone else answered and felt included in the research process. ARS is beneficial because the community can answer truthfully and provides instant research results. Additionally, researchers can collect large amounts of data quickly, in a non-threatening way while tracking individual responses anonymously. Audience Response Systems proved to be an effective tool for successfully accomplishing community-based participatory research

Artificial Intelligence-Based Drug Design and Discovery

The drug discovery process from hit-to-lead has been a challenging task that requires simultaneously optimizing numerous factors from maximizing compound activity, efficacy to minimizing toxicity and adverse reactions. Recently, the advance of artificial intelligence technique enables drugs to be efficiently purposed in silico prior to chemical synthesis and experimental evaluation. In this chapter, we present fundamental concepts of artificial intelligence and their application in drug design and discovery. The emphasis will be on machine learning and deep learning, which demonstrated extensive utility in many branches of computer-aided drug discovery including de novo drug design, QSAR (Quantitative Structure–Activity Relationship) analysis, drug repurposing and chemical space visualization. We will demonstrate how artificial intelligence techniques can be leveraged for developing chemoinformatics pipelines and presented with real-world case studies and practical applications in drug design and discovery. Finally, we will discuss limitations and future direction to guide this rapidly evolving field

DRUG-NEM: Optimizing drug combinations using single-cell perturbation response to account for intratumoral heterogeneity.

An individual malignant tumor is composed of a heterogeneous collection of single cells with distinct molecular and phenotypic features, a phenomenon termed intratumoral heterogeneity. Intratumoral heterogeneity poses challenges for cancer treatment, motivating the need for combination therapies. Single-cell technologies are now available to guide effective drug combinations by accounting for intratumoral heterogeneity through the analysis of the signaling perturbations of an individual tumor sample screened by a drug panel. In particular, Mass Cytometry Time-of-Flight (CyTOF) is a high-throughput single-cell technology that enables the simultaneous measurements of multiple ([Formula: see text]40) intracellular and surface markers at the level of single cells for hundreds of thousands of cells in a sample. We developed a computational framework, entitled Drug Nested Effects Models (DRUG-NEM), to analyze CyTOF single-drug perturbation data for the purpose of individualizing drug combinations. DRUG-NEM optimizes drug combinations by choosing the minimum number of drugs that produce the maximal desired intracellular effects based on nested effects modeling. We demonstrate the performance of DRUG-NEM using single-cell drug perturbation data from tumor cell lines and primary leukemia samples

Structural racism and odds for infant mortality among infants born in the United States 2010

Abstract OBJECTIVES: While ecological studies indicate that high levels of structural racism within US states are associated with elevated infant mortality rates, studies using individual-level data are needed. To determine whether indicators of structural racism are associated with the individual odds for infant mortality among white and black infants in the US. METHODS: We used data on 2,163,096 white and 590,081 black infants from the 2010 US Cohort Linked Birth/Infant Death Data Files. Structural racism indicators were ratios of relative proportions of blacks to whites for these domains: electoral (registered to vote and voted; state legislature representation), employment (civilian labor force; employed; in management; with a bachelor\u27s degree), and justice system (sentenced to death; incarcerated). Multilevel logistic regression was used to determine whether structural racism indicators were risk factors of infant mortality. RESULTS: Compared to the lowest tertile ratio of relative proportions of blacks to whites with a bachelor\u27s degree or higher-indicative of low structural racism-black infants, but not whites, in states with moderate (OR = 1.12, 95% CI = 0.94, 1.32) and high tertiles (OR = 1.25, 95% CI = 1.03, 1.51) had higher odds of infant mortality. CONCLUSIONS: Educational and judicial indicators of structural racism were associated with infant mortality among blacks. Decreasing structural racism could prevent black infant deaths

Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder

PosterAutism spectrum disorder (ASD) is characterized by impairments in social communication and abnormal repetitive behavior patterns. Recent studies have shown a strong association between ASD and gastrointestinal (GI) symptomatology. Some individuals with ASD show altered reactivity to stress, as well as altered immune markers, particularly stress responsive cytokines including TNF-alpha and IL-6. To assess potential relationships between GI symptoms and stress response, we examined whether GI symptoms are associated with increases in stress-associated endocrine markers and cytokines in ASD. We also conducted exploratory analyses the examine the relationship between IL-6, TNF-alpha, cortisol, and intelligence, as well as the effects of the presence or absence of co-occurring medical conditions on the relationship between IL-6, TNF-alpha, cortisol, and GI symptoms. Given the aforementioned findings, we expected to find positive relationships between GI symptoms and biomarkers of stress, including cortisol levels, IL-6, and TNF-alpha

How does Labrador Sea Water enter the deep western boundary current?

Author Posting. © American Meteorological Society, 2008. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 38 (2008): 968-983, doi:10.1175/2007JPO3807.1.Labrador Sea Water (LSW), a dense water mass formed by convection in the subpolar North Atlantic, is an important constituent of the meridional overturning circulation. Understanding how the water mass enters the deep western boundary current (DWBC), one of the primary pathways by which it exits the subpolar gyre, can shed light on the continuity between climate conditions in the formation region and their downstream signal. Using the trajectories of (profiling) autonomous Lagrangian circulation explorer [(P)ALACE] floats, operating between 1996 and 2002, three processes are evaluated for their role in the entry of Labrador Sea Water in the DWBC: 1) LSW is formed directly in the DWBC, 2) eddies flux LSW laterally from the interior Labrador Sea to the DWBC, and 3) a horizontally divergent mean flow advects LSW from the interior to the DWBC. A comparison of the heat flux associated with each of these three mechanisms suggests that all three contribute to the transformation of the boundary current as it transits the Labrador Sea. The formation of LSW directly in the DWBC and the eddy heat flux between the interior Labrador Sea and the DWBC may play leading roles in setting the interannual variability of the exported water mass.We are also grateful to the NSF for their support of this research

Take-Wait-stop: A Patient-Centered Strategy for Writing PRN Medication Instructions

Recent studies have linked patient misunderstanding of label instructions for as needed (PRN) medications to dosing errors. This study conducted a preliminary field test of patient-centered PRN label instructions. Patients participated in a hypothetical dosing experiment and were randomized to a patient-centered label (referred to as “Take-Wait-Stop”) or standard label. Participants were asked to demonstrate dosing the medicine over 24 hours. Three types of independent dosing errors were measured: (a) taking more than two pills at one time, (b) exceeding the maximum daily dose, and (c) waiting fewer than 4 hours between doses. Generalized linear models were used to assess the association between label type, health literacy, and sociodemographic characteristics. Participants' mean age was 39.8 years, 62.1% were female, 43.7% were White, and 72.4% had adequate literacy. Of participants, 31.8% who were shown the standard label demonstrated taking in excess of 6 pills in 24 hours compared with only 14.0% of participants who were shown the Take-Wait-Stop label (p = .05). Overall, only 1 person demonstrated he would take more than 2 pills in a single dose. Of the standard label group, 20.5% demonstrated dosing intervals of fewer than 4 hours compared with 23.3% of the Take-Wait-Stop label group (p = .75). In a multivariate model, participants who were exposed to the standard label were 2.5 times more likely to exceed the recommended maximum daily dose (95% CI [1.05, 7.70], p = .03). The Take-Wait-Stop label was beneficial in preventing participants from exceeding the maximum dose in 24 hours, although it did not significantly reduce other dosing errors

Prosocial effects of oxytocin in two mouse models of autism spectrum disorders

Clinical evidence suggests that oxytocin treatment improves social deficits and repetitive behavior in autism spectrum disorders (ASDs). However, the neuropeptide has a short plasma half-life and poor ability to penetrate the blood-brain barrier. In order to facilitate the development of more bioavailable oxytocinergic compounds as therapeutics to treat core ASD symptoms, small animal models must be validated for preclinical screens. This study examined the preclinical utility of two inbred mouse strains, BALB/cByJ and C58/J, that exhibit phenotypes relevant to core ASD symptoms. Mice from both strains were intraperitoneally administered oxytocin, using either acute or sub-chronic regimens. Acute oxytocin did not increase sociability in BALB/cByJ; however, sub-chronic oxytocin had significant prosocial effects in both BALB/cByJ and C58/J. Increased sociability was observed 24 hours following the final oxytocin dose in BALB/cByJ, while prosocial effects of oxytocin emerged 1–2 weeks post-treatment in C58/J. Furthermore, acute oxytocin decreased motor stereotypy in C58/J and did not induce hypoactivity or anxiolytic-like effects in an open field test. This study demonstrates that oxytocin administration can attenuate social deficits and repetitive behavior in mouse models of ASD, dependent on dose regimen and genotype. These findings provide validation of the BALB/cByJ and C58/J models as useful platforms for screening novel drugs for intervention in ASDs and for elucidating the mechanisms contributing to the prosocial effects of oxytocin

The Vehicle, Fall 1987

Table of Contents Sketches in the SunRodger L. Patiencepage 3 Reflecting PoolRob Montgomerypage 5 Grandpa\u27s Porcelain DollRichard E. Hallpage 6 Tintype 1837Catherine Friemannpage 6 PhotographSteven M. Beamerpage 7 Washerwoman\u27s SongBob Zordanipage 8 Scrambled Eggs for D.O.Lynne A. Rafoolpage 8 my mother would sayMonica Grothpage 9 Retired by His ChildrenDan Von Holtenpage 10 I am the oldestMonica Grothpage 11 Ice on WheatRob Montgomerypage 12 The Nature of the RoseTroy Mayfieldpage 12 Past NebraskaDan Hornbostelpage 13 Five Minute Jamaican VacationChristy Dunphypage 14 PhotographSteven M. Beamerpage 14 The Angry PoemChristy Dunphypage 15 Road UnfamiliarChristy Dunphypage 15 raised voicesMonica Grothpage 16 Old Ladies & MiniskirtsKara Shannonpage 17 FreakspeakBob Zordanipage 18 PortraitDan Von Holtenpage 18 Mobile VacuumKathleen L. Fairfieldpage 19 Rev. Fermus DickSteve Hagemannpage 20 PhotographSteven M. Beamerpage 21 What\u27s the Name of That Flower?Richard Jesse Davispage 22 RequestChristy Dunphypage 23 SketchPaul Seabaughpage 24 ExperiencedMarilyn Wilsonpage 26 Leaving: Two ViewsTina Phillipspage 27 AntaeusDan Von Holtenpage 28 Misogyny at 19J. D. Finfrockpage 29 A Mental CrippleSteve Hagemannpage 32 AssociationsRhonda Ealypage 33 Banana BreadGail Bowerpage 34 Bill and JackBradford B. Autenpage 35 After Image No. 2Rob Montgomerypage 35 VrrooomBeth Goodmanpage 36 Mr. Modern LoverMolly Maddenpage 36 TravelogueRodger L. Patiencepage 37 Down the HighwayJoan Sebastianpage 38 A Retread HeavenRob Montgomerypage 41 StuporDan Von Holtenpage 42 Love Poem After a Seizure in Your BedBob Zordanipage 43 PalsyChristy Dunphypage 44 Interview with Mr. MatthewsBob Zordanipage 45 Chasing Down Hot Air Balloons on a Sunday MorningRob Montgomerypage 48https://thekeep.eiu.edu/vehicle/1049/thumbnail.jp