Hardware thread management modeling for precision timed processors

Studies recently and currently in progress address timing demands for Cyber Physical Systems (CPS) applications. Certain areas of research seek to modify modern computer architecture to meet the needs of CPS applications. Moreover, specific modifications in current computer architecture have produced newer computer architectures and processors, such as precision timed (PRET) processors. This thesis focuses on identifying, modeling, and simulating thread management methods in hardware used by the current open-source PRET soft processor, the MultiFire

Field-deployable, quantitative, rapid identification of active Ebola virus infection in unprocessed blood

The West African Ebola virus outbreak underlined the importance of delivering mass diagnostic capability outside the clinical or primary care setting in effectively containing public health emergencies caused by infectious disease. Yet, to date, there is no solution for reliably deploying at the point of need the gold standard diagnostic method, real time quantitative reverse transcription polymerase chain reaction (RT- qPCR), in a laboratory infrastructure-free manner. In this proof of principle work, we demonstrate direct performance of RT-qPCR on fresh blood using far-red fluorophores to resolve fluorogenic signal inhibition and controlled, rapid freeze/thawing to achieve viral genome extraction in a single reaction chamber assay. The resulting process is entirely free of manual or automated sample pre-processing, requires no microfluidics or magnetic/mechanical sample handling and thus utilizes low cost consumables. This enables a fast, laboratory infrastructure-free, minimal risk and simple standard operating procedure suited to frontline, field use. Developing this novel approach on recombinant bacteriophage and recombinant human immunodeficiency virus (HIV; Lentivirus), we demonstrate clinical utility in symptomatic EBOV patient screening using live, infectious Filoviruses and surrogate patient samples. Moreover, we evidence assay co-linearity independent of viral particle structure that may enable viral load quantification through pre-calibration, with no loss of specificity across an 8 log- linear maximum dynamic range. The resulting quantitative rapid identification (QuRapID) molecular diagnostic platform, openly accessible for assay development, meets the requirements of resource- limited countries and provides a fast response solution for mass public health screening against emerging biosecurity threats

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

The use of invertebrate body burdens to predict ecological effects of metal mixtures in mining-impacted waters

The present study investigated whether invertebrate body burdens can be used to predict metal-induced effects on aquatic invertebrate communities. Total dissolved metal levels and four invertebrate taxa (Leuctra sp., Simuliidae, Rhithrogena sp. and Perlodidae) were sampled in 36 headwater streams located in the north-west part of England. Using the River Invertebrate Prediction and Classification System (RIVPACS) taxonomic completeness of invertebrate communities was assessed. Quantile regression was used to relate invertebrate body burdens to a maximum (90th quantile) ecological response, both for all metals separately and in mixtures. Significant relations between Cu, Zn and Pb burdens in Leuctra sp. (Zn, Pb), Simuliidae (Zn, Pb), Rhithrogena sp. (Cu, Zn, Cu + Zn) and Perlodidae (Zn) and both taxonomic completeness (O/E taxa) and Biological Monitoring Working Party index scores (O/E BMWP) were observed. Correspondingly the obtained Cu-Zn mixture model an acceptable impact of 5% change in taxonomic completeness is expected at Rhithrogena sp. body burdens of 1.9 mu mol g(-1) Cu (121 mu g g(-1) Cu) in case of low Zn bioavailability (Rhithrogena sp. Zn body burden of 2.9 mu mol g(-1) or 190 mu g g(-1)), which will drop to 0.30 mu mol g(-1) Cu (19.1 mu g g(-1) Cu) in case of higher Zn bioavailability (Zn body burden of 72.6 mu mol g(-1) or 4747 mu g g(-1)). For Zn, 5% change in taxonomic completeness is expected at Rhithrogena sp. body burdens of 76.4 mu mol g(-1) Zn (4995 mu g g(-1) Zn) in case of low Cu bioavailability (Cu body burden of 0.19 mu mol g(-1) or 12.1 mu g g(-1)), which will drop to 6.6 mu mol g(-1) Zn (432 mu g g(-1) Zn) at higher Cu bioavailability (Cu body burden of 1.74 mu mol g(-1) or 111 mu g g(-1)). Overall, the present study concludes that invertebrate body burdens can be used to (1) predict metal-induced ecological effects and (2) to derive critical burdens for the protection of aquatic invertebrate communities

Chalcogenide Hybrid Inorganic/Organic Polymers: Ultrahigh Refractive Index Polymers for Infrared Imaging

We report on the preparation of ultrahigh refractive index polymers via the inverse vulcanization of elemental sulfur, selenium, and 1,3-diisopropenylbenzene for use as novel transmissive materials for mid-infrared (IR) imaging applications. Poly­(sulfur-<i>random</i>-selenium-<i>random</i>-(1,3-diisopropenylbenzene)) (poly­(S-<i>r</i>-Se-<i>r</i>-DIB) terpolymer materials from this process exhibit the highest refractive index of any synthetic polymer (<i>n</i> > 2.0) and excellent IR transparency, which can be directly tuned by terpolymer composition. Sulfur or selenium containing (co)­polymers prepared via inverse vulcanization can be described as Chalcogenide Hybrid Inorganic/Organic Polymers (CHIPs) and are polymeric analogues to wholly inorganic Chalcogenide Glasses (ChGs), which are commonly used as transmissive materials in mid-IR imaging. Finally, we demonstrate that CHIPs composed of (poly­(S-<i>r</i>-Se-<i>r</i>-DIB) can be melt processed into windows that enabled high quality mid-IR thermal imaging of human subjects and highly resolved imaging of human vasculature