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INTRODUCTION: Blood‐based biomarkers are a cost‐effective and minimally invasive method for diagnosing the early and preclinical stages of amyloid positivity (AP). Our study aims to investigate our novel immunoprecipitation‐immunoassay (IP‐IA) as a test for predicting cognitive decline. METHODS: We measured levels of amyloid beta (Aβ)X‐40 and AβX‐42 in immunoprecipitated eluates from the DELCODE cohort. Receiver‐operating characteristic (ROC) curves, regression analyses, and Cox proportional hazard regression models were constructed to predict AP by Aβ42/40 classification in cerebrospinal fluid (CSF) and conversion to mild cognitive impairment (MCI) or dementia. RESULTS: We detected a significant correlation between AßX‐42/X‐40 in plasma and CSF (r = 0.473). Mixed‐modeling analysis revealed a substantial prediction of AßX‐42/X‐40 with an area under the curve (AUC) of 0.81 for AP (sensitivity: 0.79, specificity: 0.74, positive predictive value [PPV]: 0.71, negative predictive value [NPV]: 0.81). In addition, lower AβX‐42/X‐40 ratios were associated with negative PACC5 slopes, suggesting cognitive decline. DISCUSSION: Our results suggest that assessing the plasma AβX‐42/X‐40 ratio via our semiautomated IP‐IA is a promising biomarker when examining patients with early or preclinical AD. Highlights: New plasma Aβ42/Aβ40 measurement using immunoprecipitation–immunoassayPlasma Aβ42/Aβ40 associated with longitudinal cognitive declinePromising biomarker to detect subjective cognitive decline at‐risk for brain amyloid positivity [ABSTRACT FROM AUTHOR]

Background: The quantitative analysis of biomarker proteins in the cerebrospinal fluid (CSF) substantiates the clinical diagnosis of Alzheimer´s disease (AD). A substantial problem in the early diagnosis of AD is that clinical symptoms as measured by neuropsychological tests appear only after massive cell loss has already occurred in the brain. However, when the disease manifests, abeta‐ and tau‐protein levels have already become static. In this study, we asked whether concentrations of the astrocyte‐derived proteins glial fibrillary acidic protein (GFAP) and S100 calcium‐binding protein B (S100B) in CSF might serve as markers of pathophysiological events and astrocyte reactivation in the course of AD. Although, there are some previously studies reporting high GFAP levels in cerebrospinal fluid of AD group, the CSF levels of GFAP and S100B in the early course of the AD have not been reported. Methods: We measured the levels of GFAP and S100B in the CSF of healthy control subjects (n = 90), first degree relatives of AD (parent or sibling, n = 46), subjective memory decline (SCD) (n = 211), mild cognitive impairment (MCI) (n = 114) and AD (n = 65) patients in a well‐structured cohort (DELCODE Cohort), which has a larger sample size than previous studies. Results: After comparing the CSF levels of GFAP in the study groups, we found that healthy controls had significantly lower GFAP levels than AD patients (p = 0.001, Figure 1) and the MCI patients (p = 0,004, Figure 1). It might prove to be a very important evidence of the role of astrogliosis in early stages. Furthermore, no significantly differences were found in levels of S100B, although S100B mean values show also gradual increasing from SCD to AD (Figure 2). As a note to the reader, we also found that there was low correlation between the levels of glial markers (GFAP und S100B) and markers of classical biomarkers (Aβ‐42, Ratio Aβ‐42/Aβ‐40, Total‐τ, Phospho‐τ‐181) of neurodegeneration in the disease course. Conclusion: This result may prove the role of early reactive astrocytes in early stages of disease. And this finding could lead to develop another treatment concepts targeting the early reactive astrocytes. [ABSTRACT FROM AUTHOR]

The data currently described was generated within the EU/FP7 HeCaToS project (Hepatic and Cardiac Toxicity Systems modeling). The project aimed to develop an in silico prediction system to contribute to drug safety assessment for humans. For this purpose, multi-omics data of repeated dose toxicity were obtained for 10 hepatotoxic and 10 cardiotoxic compounds. Most data were gained from in vitro experiments in which 3D microtissues (either hepatic or cardiac) were exposed to a therapeutic (physiologically relevant concentrations calculated through PBPK-modeling) or a toxic dosing profile (IC20 after 7 days). Exposures lasted for 14 days and samples were obtained at 7 time points (therapeutic doses: 2-8-24-72-168-240-336 h; toxic doses 0-2-8-24-72-168-240 h). Transcriptomics (RNA sequencing & microRNA sequencing), proteomics (LC-MS), epigenomics (MeDIP sequencing) and metabolomics (LC-MS & NMR) data were obtained from these samples. Furthermore, functional endpoints (ATP content, Caspase3/7 and O2 consumption) were measured in exposed microtissues. Additionally, multi-omics data from human biopsies from patients are available. This data is now being released to the scientific community through the BioStudies data repository (https://www.ebi.ac.uk/biostudies/). [ABSTRACT FROM AUTHOR]

This paper describes results from a study evaluating stringless paving using a combination of global positioning and laser technologies. A concrete paver manufacturer and a machine guidance solution provider developed this technology and successfully implemented it on construction earthmoving and grading projects. Concrete paving is a new area for considering this technology. A concrete paving contractor in Iowa agreed to test the stringless paving technology on two challenging concrete paving projects located in Washington County, Iowa during the summer of 2003. The research team from Iowa State University monitored the guidance and elevation conformance to the original design. They employed a combination of physical depth checks, surface location and elevation surveys, concrete yield checks, and physical survey of the control stakes and string line elevations. A final check on profile of the pavement surface was accomplished by the use of the Iowa Department of Transportation Light Weight Surface Analyzer. Due to the speed of paving and the rapid changes in terrain, the laser technology was abandoned for this project. Total control of the guidance and elevation controls on the slip form paver were moved from string line to a global positioning system (GPS). Results indicate that GPS control is a feasible approach to controlling a concrete paver. Further enhancements are needed in the physical features of the slip form paver hydraulic system controls and in the computer program for controlling elevation. DOI: 10.1061/(ASCE)CO.1943-7862.0000083 CE Database subject headings: Concrete pavements; Geographic information systems; Global positioning; Robotics; Automation; Portland cement.