Nitrogen retention in the riparian zone of watersheds underlain by discontinuous permafrost

Thesis (M.S.) University of Alaska Fairbanks, 2005Riparian zones function as important ecotones for reducing nitrate concentration in groundwater and inputs into streams. In the boreal forest of interior Alaska, permafrost confines subsurface flow through the riparian zone to shallow organic horizons, where plant uptake of nitrate and denitrification are typically high. Two research questions were addressed in this study: 1) how does riparian zone nitrogen retention vary in watersheds underlain by discontinuous permafrost, and 2) what is the contribution of denitrification to riparian zone nitrogen retention? To estimate the contribution of the riparian zone to watershed nitrogen retention, I analyzed groundwater chemistry using an end-member mixing model. To assess the importance of denitrification as a mechanism of nitrogen retention, I conducted field denitrification assays using the acetylene block technique. Over the summer, nitrogen retention averaged 0.75 and 0.22 mmol N m⁻² d⁻¹ in low and high permafrost watersheds, respectively. Compared with the fluvial export of nitrogen, the retention rate of nitrogen in the riparian zone is 10 - 15% of the loss rate in stream flow. Denitrification accounted for a small proportion (3%) of total nitrogen retention in the riparian zone. Variation in nitrogen retention between watersheds did not account for differences in stream nitrate concentration between watersheds.Introduction -- Factors controlling denitrification -- Riparian zones as nutrient filters -- Models of riparian zone function -- Permafrost and hydrology -- Caribou Poker Creeks Research Watershed (CPCRW) -- References -- Nitrogen retention in the riparian zone of watersheds underlain by discontinuous permafrost -- Conclusions -- References

The effects of permafrost degradation on soil carbon dynamics in Alaska's boreal region

Dissertation (Ph.D.) University of Alaska Fairbanks, 2010High-latitude regions store large quantities of organic carbon (C) in permafrost soils and peatlands, accounting for nearly half of the global belowground C pool. Projected climate warming over the next century will likely drive widespread thawing of near-surface permafrost and mobilization of soil C from deep soil horizons. However, the processes controlling soil C accumulation and loss following permafrost thaw are not well understood. To improve our understanding of these processes, I examined the effects of permafrost thaw on soil C dynamics in forested upland and peatland ecosystems of Alaska's boreal region. In upland forests, soil C accumulation and loss was governed by the complex interaction of wildfire and permafrost. Fluctuations in active layer depth across stand age and fire cycles determined the proportion of soil C in frozen or unfrozen soil, and in turn, the vulnerability of soil C to decomposition. Under present-day climate conditions, the presence of near-surface permafrost aids C stabilization through the upward movement of the permafrost table with post-fire ecosystem recovery. However, sensitivity analyses suggest that projected increases in air temperature and fire severity will accelerate permafrost thaw and soil C loss from deep mineral horizons. In the lowlands, permafrost thaw and collapse-scar bog formation resulted in the dramatic redistribution of soil water, modifying soil thermal and C dynamics. Water impoundment in collapse-scar bogs enhanced soil C accumulation in shallow peat horizons, while allowing for high rates of soil C loss from deep inundated peat horizons. Accumulation rates at the surface were not sufficient to balance deep C losses, resulting in a net loss of 26 g C m⁻² y⁻¹ from the entire peat column during the 3000 years following thaw. Findings from these studies highlight the vulnerability of soil C in Alaska's boreal region to future climate warming and permafrost thaw. As a result, permafrost thaw and soil C release from boreal soils to the atmosphere should function as a positive feedback to the climate system

Th1 Cytokine-Secreting Recombinant Mycobacterium bovis Bacillus Calmette-Guérin and Prospective Use in Immunotherapy of Bladder Cancer

Intravesical instillation of Mycobacterium bovis bacillus Calmette-Guérin (BCG) has been used for treating bladder cancer for 3 decades. However, BCG therapy is ineffective in approximately 30–40% of cases. Since evidence supports the T helper type 1 (Th1) response to be essential in BCG-induced tumor destruction, studies have focused on enhancing BCG induction of Th1 immune responses. Although BCG in combination with Th1 cytokines (e.g., interferon-α) has demonstrated improved efficacy, combination therapy requires multiple applications and a large quantity of cytokines. On the other hand, genetic manipulation of BCG to secrete Th1 cytokines continues to be pursued with considerable interest. To date, a number of recombinant BCG (rBCG) strains capable of secreting functional Th1 cytokines have been developed and demonstrated to be superior to BCG. This paper discusses current rBCG research, concerns, and future directions with an intention to inspire the development of this very promising immunotherapeutic modality for bladder cancer

Deep learning-based algorithm for assessment of knee osteoarthritis severity in radiographs matches performance of radiologists

A fully-automated deep learning algorithm matched performance of radiologists in assessment of knee osteoarthritis severity in radiographs using the Kellgren-Lawrence grading system. To develop an automated deep learning-based algorithm that jointly uses Posterior-Anterior (PA) and Lateral (LAT) views of knee radiographs to assess knee osteoarthritis severity according to the Kellgren-Lawrence grading system. We used a dataset of 9739 exams from 2802 patients from Multicenter Osteoarthritis Study (MOST). The dataset was divided into a training set of 2040 patients, a validation set of 259 patients and a test set of 503 patients. A novel deep learning-based method was utilized for assessment of knee OA in two steps: (1) localization of knee joints in the images, (2) classification according to the KL grading system. Our method used both PA and LAT views as the input to the model. The scores generated by the algorithm were compared to the grades provided in the MOST dataset for the entire test set as well as grades provided by 5 radiologists at our institution for a subset of the test set. The model obtained a multi-class accuracy of 71.90% on the entire test set when compared to the ratings provided in the MOST dataset. The quadratic weighted Kappa coefficient for this set was 0.9066. The average quadratic weighted Kappa between all pairs of radiologists from our institution who took a part of study was 0.748. The average quadratic-weighted Kappa between the algorithm and the radiologists at our institution was 0.769. The proposed model performed demonstrated equivalency of KL classification to MSK radiologists, but clearly superior reproducibility. Our model also agreed with radiologists at our institution to the same extent as the radiologists with each other. The algorithm could be used to provide reproducible assessment of knee osteoarthritis severity

Importance of soil thermal regime in terrestrial ecosystem carbon dynamics in the circumpolar north

© The Author(s), 2016. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Global and Planetary Change 142 (2016): 28-40, doi:10.1016/j.gloplacha.2016.04.011.In the circumpolar north (45-90°N), permafrost plays an important role in vegetation and carbon (C) dynamics. Permafrost thawing has been accelerated by the warming climate and exerts a positive feedback to climate through increasing soil C release to the atmosphere. To evaluate the influence of permafrost on C dynamics, changes in soil temperature profiles should be considered in global C models. This study incorporates a sophisticated soil thermal model (STM) into a dynamic global vegetation model (LPJ-DGVM) to improve simulations of changes in soil temperature profiles from the ground surface to 3 m depth, and its impacts on C pools and fluxes during the 20th and 21st centuries.With cooler simulated soil temperatures during the summer, LPJ-STM estimates ~0.4 Pg C yr-1 lower present-day heterotrophic respiration but ~0.5 Pg C yr-1 higher net primary production than the original LPJ model resulting in an additional 0.8 to 1.0 Pg C yr-1 being sequestered in circumpolar ecosystems. Under a suite of projected warming scenarios, we show that the increasing active layer thickness results in the mobilization of permafrost C, which contributes to a more rapid increase in heterotrophic respiration in LPJ-STM compared to the stand-alone LPJ model. Except under the extreme warming conditions, increases in plant production due to warming and rising CO2, overwhelm the enhanced ecosystem respiration so that both boreal forest and arctic tundra ecosystems remain a net C sink over the 21st century. This study highlights the importance of considering changes in the soil thermal regime when quantifying the C budget in the circumpolar north.This research is supported by funded projects to Q. Z. National Science Foundation (NSF- 1028291 and NSF- 0919331), the NSF Carbon and Water in the Earth Program (NSF-0630319), the NASA Land Use and Land Cover Change program (NASA- NNX09AI26G), and Department of Energy (DE-FG02-08ER64599).2017-05-0

Automated Grading of Radiographic Knee Osteoarthritis Severity Combined with Joint Space Narrowing

The assessment of knee osteoarthritis (KOA) severity on knee X-rays is a central criteria for the use of total knee arthroplasty. However, this assessment suffers from imprecise standards and a remarkably high inter-reader variability. An algorithmic, automated assessment of KOA severity could improve overall outcomes of knee replacement procedures by increasing the appropriateness of its use. We propose a novel deep learning-based five-step algorithm to automatically grade KOA from posterior-anterior (PA) views of radiographs: (1) image preprocessing (2) localization of knees joints in the image using the YOLO v3-Tiny model, (3) initial assessment of the severity of osteoarthritis using a convolutional neural network-based classifier, (4) segmentation of the joints and calculation of the joint space narrowing (JSN), and (5), a combination of the JSN and the initial assessment to determine a final Kellgren-Lawrence (KL) score. Furthermore, by displaying the segmentation masks used to make the assessment, our algorithm demonstrates a higher degree of transparency compared to typical "black box" deep learning classifiers. We perform a comprehensive evaluation using two public datasets and one dataset from our institution, and show that our algorithm reaches state-of-the art performance. Moreover, we also collected ratings from multiple radiologists at our institution and showed that our algorithm performs at the radiologist level. The software has been made publicly available at https://github.com/MaciejMazurowski/osteoarthritis-classification

Global survey of the frequency of atrial fibrillation-associated stroke: embolic stroke of undetermined source global registry

Background and Purpose—Atrial fibrillation (AF) is increasingly recognized as the single most important cause of disabling ischemic stroke in the elderly. We undertook an international survey to characterize the frequency of AF-associated stroke, methods of AF detection, and patient features. Methods—Consecutive patients hospitalized for ischemic stroke in 2013 to 2014 were surveyed from 19 stroke research centers in 19 different countries. Data were analyzed by global regions and World Bank income levels. Results—Of 2144 patients with ischemic stroke, 590 (28%; 95% confidence interval, 25.6–29.5) had AF-associated stroke, with highest frequencies in North America (35%) and Europe (33%) and lowest in Latin America (17%). Most had a history of AF before stroke (15%) or newly detected AF on electrocardiography (10%); only 2% of patients with ischemic stroke had unsuspected AF detected by poststroke cardiac rhythm monitoring. The mean age and 30-day mortality rate of patients with AF-associated stroke (75 years; SD, 11.5 years; 10%; 95% confidence interval, 7.6–12.6, respectively) were substantially higher than those of patients without AF (64 years; SD, 15.58 years; 4%; 95% confidence interval, 3.3–5.4; P<0.001 for both comparisons). There was a strong positive correlation between the mean age and the frequency of AF (r=0.76; P=0.0002). Conclusions—This cross-sectional global sample of patients with recent ischemic stroke shows a substantial frequency of AF-associated stroke throughout the world in proportion to the mean age of the stroke population. Most AF is identified by history or electrocardiography; the yield of conventional short-duration cardiac rhythm monitoring is relatively low. Patients with AF-associated stroke were typically elderly (>75 years old) and more often women

Arterial elasticity imaging: comparison of finite-element analysis models with high-resolution ultrasound speckle tracking

<p>Abstract</p> <p>Background</p> <p>The nonlinear mechanical properties of internal organs and tissues may be measured with unparalleled precision using ultrasound imaging with phase-sensitive speckle tracking. The many potential applications of this important noninvasive diagnostic approach include measurement of arterial stiffness, which is associated with numerous major disease processes. The accuracy of previous ultrasound measurements of arterial stiffness and vascular elasticity has been limited by the relatively low strain of nonlinear structures under normal physiologic pressure and the measurement assumption that the effect of the surrounding tissue modulus might be ignored in both physiologic and pressure equalized conditions.</p> <p>Methods</p> <p>This study performed high-resolution ultrasound imaging of the brachial artery in a healthy adult subject under normal physiologic pressure and the use of external pressure (pressure equalization) to increase strain. These ultrasound results were compared to measurements of arterial strain as determined by finite-element analysis models with and without a surrounding tissue, which was represented by homogenous material with fixed elastic modulus.</p> <p>Results</p> <p>Use of the pressure equalization technique during imaging resulted in average strain values of 26% and 18% at the top and sides, respectively, compared to 5% and 2%, at the top and sides, respectively, under physiologic pressure. In the artery model that included surrounding tissue, strain was 19% and 16% under pressure equalization versus 9% and 13% at the top and sides, respectively, under physiologic pressure. The model without surrounding tissue had slightly higher levels of strain under physiologic pressure compared to the other model, but the resulting strain values under pressure equalization were > 60% and did not correspond to experimental values.</p> <p>Conclusions</p> <p>Since pressure equalization may increase the dynamic range of strain imaging, the effect of the surrounding tissue on strain should be incorporated into models of arterial strain, particularly when the pressure equalization technique is used.</p

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p&lt;0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p&lt;0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p&lt;0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology

Lead Slowing Down Spectrometer Status Report

This report documents the progress that has been completed in the first half of FY2012 in the MPACT-funded Lead Slowing Down Spectrometer project. Significant progress has been made on the algorithm development. We have an improve understanding of the experimental responses in LSDS for fuel-related material. The calibration of the ultra-depleted uranium foils was completed, but the results are inconsistent from measurement to measurement. Future work includes developing a conceptual model of an LSDS system to assay plutonium in used fuel, improving agreement between simulations and measurement, design of a thorium fission chamber, and evaluation of additional detector techniques