1,391 research outputs found

    Medieval death trip

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    Dissertation supervisor: Dr. Trudy Lewis.Includes vita.This dissertation presents two related works, one creative non-fiction and the other fiction, that engage in representing and adapting medieval texts. The non-fiction work consists of annotated transcripts of twelve episodes of a podcast entitled Medieval Death Trip. These episodes provide commentary on selected medieval texts drawn primarily from monastic chronicles but including other genres as well, each of which is presented as a featured performative reading in the middle of the episode enhanced by audio production that adds music and sound effects. The purpose of this show is to help a non-expert audience appreciate and become engaged with these rather remote and sometimes inaccessible texts. The fiction is a linked collection of short narratives entitled The Libellus de Mutationis, whose narrator is a monk writing tales of changes and transformations he has heard of as a way of justifying the fictionalizations he has wrought in a work of hagiography that he has completed. The fiction imitates elements of medieval rhetoric and narrative tropes, and in its own way offers novel variations on the same kinds of authentic texts presented in the podcast episodes.Includes bibliographical references (pages 277-285)

    The AMD Rome Memory Barrier

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    With the rapid growth of AMD as a competitor in the CPU industry, it is imperative that high-performance and architectural engineers analyze new AMD CPUs. By understanding new and unfamiliar architectures, engineers are able to adapt their algorithms to fully utilize new hardware. Furthermore, engineers are able to anticipate the limitations of an architecture and determine when an alternate platform is desirable for a particular workload. This paper presents results which show that the AMD "Rome" architecture performance suffers once an application's memory bandwidth exceeds 37.5 GiB/s for integer-heavy applications, or 100 GiB/s for floating-point-heavy workloads. Strong positive correlations between memory bandwidth and CPI are presented, as well as strong positive correlations between increased memory load and time-to-completion of benchmarks from the SPEC CPU2017 benchmark suites.Comment: Very, very early draft for IEEE SoutheastCon 2017, 9 pages (need to get down to 8), 6 figures, 7 table

    Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia

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    Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic sub-Saharan Africa, where the greatest sickle-cell burden exists, remain unknown. In vitro studies suggest hydroxyurea could increase malaria severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM (Novel use Of Hydroxyurea in an African Region with Malaria) was a randomized, double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda, comparing hydroxyurea to placebo at 20 ± 2.5 mg/kg per day for 12 months. The primary outcome was incidence of clinical malaria. Secondary outcomes included SCA-related adverse events (AEs), clinical and laboratory effects, and hematological toxicities. Children received either hydroxyurea (N = 104) or placebo (N = 103). Malaria incidence did not differ between children on hydroxyurea (0.05 episodes per child per year; 95% confidence interval [0.02, 0.13]) vs placebo (0.07 episodes per child per year [0.03, 0.16]); the hydroxyurea/placebo malaria incidence rate ratio was 0.7 ([0.2, 2.7]; P = .61). Time to infection also did not differ significantly between treatment arms. A composite SCA-related clinical outcome (vaso-occlusive painful crisis, dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) was less frequent with hydroxyurea (45%) than placebo (69%; P = .001). Children receiving hydroxyurea had significantly increased hemoglobin concentration and fetal hemoglobin, with decreased leukocytes and reticulocytes. Serious AEs, sepsis episodes, and dose-limiting toxicities were similar between treatment arms. Three deaths occurred (2 hydroxyurea, 1 placebo, and none from malaria). Hydroxyurea treatment appears safe for children with SCA living in malaria-endemic sub-Saharan Africa, without increased severe malaria, infections, or AEs. Hydroxyurea provides SCA-related laboratory and clinical efficacy, but optimal dosing and monitoring regimens for Africa remain undefined. This trial was registered at www.clinicaltrials.gov as #NCT01976416

    A Study of Alaska's Housing Programs

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    Prepared for Legislative and Audit Committee Alaska State LegislatureYe

    Design and rationale of the B-lines lung ultrasound guided emergency department management of acute heart failure (BLUSHED-AHF) pilot trial

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    Background Medical treatment for acute heart failure (AHF) has not changed substantially over the last four decades. Emergency department (ED)-based evidence for treatment is limited. Outcomes remain poor, with a 25% mortality or re-admission rate within 30 days post discharge. Targeting pulmonary congestion, which can be objectively assessed using lung ultrasound (LUS), may be associated with improved outcomes. Methods BLUSHED-AHF is a multicenter, randomized, pilot trial designed to test whether a strategy of care that utilizes a LUS-driven treatment protocol outperforms usual care for reducing pulmonary congestion in the ED. We will randomize 130 ED patients with AHF across five sites to, a) a structured treatment strategy guided by LUS vs. b) a structured treatment strategy guided by usual care. LUS-guided care will continue until there are ≤15 B-lines on LUS or 6h post enrollment. The primary outcome is the proportion of patients with B-lines ≤ 15 at the conclusion of 6 h of management. Patients will continue to undergo serial LUS exams during hospitalization, to better understand the time course of pulmonary congestion. Follow up will occur through 90 days, exploring days-alive-and-out-of-hospital between the two arms. The study is registered on ClinicalTrials.gov (NCT03136198). Conclusion If successful, this pilot study will inform future, larger trial design on LUS driven therapy aimed at guiding treatment and improving outcomes in patients with AHF

    A mass spectrometry-based approach to distinguish annular and specific lipid binding to membrane proteins

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    Membrane proteins engage in a variety of contacts with theirsurrounding lipids, but distinguishing between specifically boundlipids, and non-specific annular interactionsis a challenging problem. Applying native mass spectrometry to three membrane protein complexes with different lipid binding properties, we explore the ability of detergents to compete with lipids bound in different environments. We show that lipids in annular positions on the Presenilin Homologue protease are subject to constant exchange with detergent. Bycontrast,detergent-resistantlipids bound at the dimer interface in the Leucine transportershowdecreased koffrates in molecular dynamics simulations.Turning tothe lipid flippase MurJ, we findthat addition of the natural substrate lipid-II results in the formation of a 1:1 protein-lipid complex, where the lipid cannot be displaced by detergentfromthe highly protected active site.In summary, we distinguish annular from non-annular lipids based on their exchange rates in solution. [Abstract copyright: © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

    Predicting Hemolytic Uremic Syndrome and Renal Replacement Therapy in Shiga Toxin-producing Escherichia coli-infected Children.

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    BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care. METHODS: We conducted a multicenter, historical cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children agedeligible. RESULTS: Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors (all shown as odds ratio [OR] with 95% confidence interval [CI]) of HUS included younger age (0.77 [.69-.85] per year), leukocyte count ≥13.0 × 103/μL (2.54 [1.42-4.54]), higher hematocrit (1.83 [1.21-2.77] per 5% increase) and serum creatinine (10.82 [1.49-78.69] per 1 mg/dL increase), platelet count \u3c250 \u3e× 103/μL (1.92 [1.02-3.60]), lower serum sodium (1.12 [1.02-1.23 per 1 mmol/L decrease), and intravenous fluid administration initiated ≥4 days following diarrhea onset (2.50 [1.14-5.46]). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (OR, 0.70 [95% CI, .54-.90]). RRT predictors (all shown as OR [95% CI]) included female sex (2.27 [1.14-4.50]), younger age (0.83 [.74-.92] per year), lower serum sodium (1.15 [1.04-1.27] per mmol/L decrease), higher leukocyte count ≥13.0 × 103/μL (2.35 [1.17-4.72]) and creatinine (7.75 [1.20-50.16] per 1 mg/dL increase) concentrations, and initial intravenous fluid administration ≥4 days following diarrhea onset (2.71 [1.18-6.21]). CONCLUSIONS: The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring

    Diabetic Kidney Disease in FVB/NJ Akita Mice: Temporal Pattern of Kidney Injury and Urinary Nephrin Excretion

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    Akita mice are a genetic model of type 1 diabetes. In the present studies, we investigated the phenotype of Akita mice on the FVB/NJ background and examined urinary nephrin excretion as a marker of kidney injury. Male Akita mice were compared with non-diabetic controls for functional and structural characteristics of renal and cardiac disease. Podocyte number and apoptosis as well as urinary nephrin excretion were determined in both groups. Male FVB/NJ Akita mice developed sustained hyperglycemia and albuminuria by 4 and 8 weeks of age, respectively. These abnormalities were accompanied by a significant increase in systolic blood pressure in 10-week old Akita mice, which was associated with functional, structural and molecular characteristics of cardiac hypertrophy. By 20 weeks of age, Akita mice developed a 10-fold increase in albuminuria, renal and glomerular hypertrophy and a decrease in the number of podocytes. Mild-to-moderate glomerular mesangial expansion was observed in Akita mice at 30 weeks of age. In 4-week old Akita mice, the onset of hyperglycemia was accompanied by increased podocyte apoptosis and enhanced excretion of nephrin in urine before the development of albuminuria. Urinary nephrin excretion was also significantly increased in albuminuric Akita mice at 16 and 20 weeks of age and correlated with the albumin excretion rate. These data suggest that: 1. FVB/NJ Akita mice have phenotypic characteristics that may be useful for studying the mechanisms of kidney and cardiac injury in diabetes, and 2. Enhanced urinary nephrin excretion is associated with kidney injury in FVB/NJ Akita mice and is detectable early in the disease process
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