ACR Accreditation for Utah Valley Hospital’s Radiation Oncology Center

Becoming an accredited clinic through the American College of Radiology (ACR) and their Radiation Oncology Practice Accreditation (ROPA) program will provide third-party evaluation of patient care to ensure the best treatment possible for patients. Talk of getting ACR accreditation has occurred in the past for Utah Valley Hospital/American Fork Hospital, but at the time it was seen as something that did not provide sufficient value vs. the cost. The recent One Intermountain restructuring is intended to unify all of the Intermountain Healthcare radiation oncology centers in Utah so the Radiation Oncology Director has set the goal that all Intermountain radiation oncology programs will be accredited. Intermountain Medical Center (IMC) and Dixie Regional Medical Center (DRMC) are currently ACR accredited and can be used as model programs. I started with an in-depth examination of our department’s workflow, documentation, and policies in order to determine where improvements to meet ACR accreditation standards could be made. I followed this up by working on implementing some of these improvements throughout the clinic and made sure they become routine and a standard in the department. An analysis of Dixie Regional Medical Center and Intermountain Medical Center’s ACR documents was performed to provide a baseline of an accredited-ACR program. Finally, a comprehensive checklist of everything that will need to be changed or implemented was presented in order to provide guidance for the future

Creating A Dynamic, Multi-Purpose Correction for Multiple Geometries and Field Sizes to Account for Off-Axis and Asymmetric Backscatter With Varian Portal Dosimetry

Intensity modulated radiation therapy and volumetric modulated arc therapy are increasingly common in radiation therapy due to their benefits of target conformity and normal tissue sparing. Due to the complexities of plan delivery and the precision required, the dose delivered must be accurately measured for quality assurance (QA). One of the most efficient ways to perform patient-specific QA when using clinical linear accelerators (linac) is to use an electronic portal imaging device (EPID). Amorphous silicon (aSi) Electronic Portal Imaging Devices (EPIDs) are attached to the linac and can provide real-time feedback with spatial resolution on the order of sub-millimeter pixel size making them very favorable for QA. However, the response to radiation in the EPIDs is not similar to that in water or soft tissue, so beam intensity profile corrections must be used and output factors specific to the imager must be collected. Additionally, when radiation exits the imager, it will travel through the support arm made up of high density materials; this non-uniform backscatter will cause the EPID to detect differences that are dependent on position and field size. To meet this need Varian Medical Systems (Palo Alto, CA) has created a 2-dimensional Portal Dosimetry Pre-Configuration (PDPC) package, which uses a 15 x 15 cm2 matrix to correct for the asymmetric and off-axis response from the non-uniform backscatter; however, because this package is optimized for a 15 x 15 cm2 field size, it may cause over or under correction of the backscattered radiation. The aim of this project is to correct the imager response as a function of field size for both off-axis variations and imaging arm backscatter variations. These corrections would be application- facing corrections, allowing them to be more robust than current corrections applied beyond EPID dosimetry calibration

A Real-time Impedance-Based Screening Assay for Drug-Induced Vascular Leakage

Vascular leakage is a serious side effect of therapies based on monoclonal antibodies or cytokines which may lead to life-threatening situations. With the steady increase of new drug development programs for large molecules, there is an urgent need for reliable tools to assess this potential liability of new medicines in a rapid and cost-effective manner. Using human umbilical vein endothelial cells (HUVECs) as a model for endothelium, we established an impedance-based assay measuring the integrity of the endothelial cell monolayer in real time. We could demonstrate that the HUVEC monolayer in our system was a relevant model as cells expressed major junctional proteins known to be responsible for maintaining tightness as well as receptors targeted by molecules known to induce vascular leakage in vivo. We assessed the time-dependent loss of barrier function using impedance and confirmed that signals obtained corresponded well to those from standard transwell assays. We assayed a series of reference molecules which led to the expected change of barrier integrity. A nonspecific cytotoxic effect could be excluded by using human fibroblasts as a nonresponder cell line. Finally, we could show reversibility of vascular permeability induced by histamine, IL-1β, or TNF-α by coincubation with established antagonists, further demonstrating relevance of this new model. Taken together, our results suggest that impedance in combination with HUVECs as a specific model can be applied to assess clinically relevant vascular leakage on an in vitro leve

Texas Water Development Board Report 120

Report on nutrients, dissolved oxygen, biochemical oxygen demand and pesticides found in surface waters in Texas in water year 1969

Texas Water Development Board Report 108

Report on providing data collected on surface water quality in Texas to analyze oxygen, nutrients, and pesticides

Hepatitis C virus and atherosclerosis: A legacy after virologic cure?

publisher: Elsevier articletitle: Hepatitis C virus and atherosclerosis: A legacy after virologic cure? journaltitle: Clinics and Research in Hepatology and Gastroenterology articlelink: http://dx.doi.org/10.1016/j.clinre.2016.09.008 content_type: article copyright: © 2016 Elsevier Masson SAS. All rights reserved

Highly Differentiated, Resting Gn-Specific Memory CD8+ T Cells Persist Years after Infection by Andes Hantavirus

In man, infection with South American Andes virus (ANDV) causes hantavirus cardiopulmonary syndrome (HCPS). HCPS due to ANDV is endemic in Southern Chile and much of Argentina and increasing numbers of cases are reported all over South America. A case-fatality rate of about 36% together with the absence of successful antiviral therapies urge the development of a vaccine. Although T-cell responses were shown to be critically involved in immunity to hantaviruses in mouse models, no data are available on the magnitude, specificity and longevity of ANDV-specific memory T-cell responses in patients. Using sets of overlapping peptides in IFN-γ ELISPOT assays, we herein show in 78 Chilean convalescent patients that Gn-derived epitopes were immunodominant as compared to those from the N- and Gc-proteins. Furthermore, while the relative contribution of the N-specific response significantly declined over time, Gn-specific responses remained readily detectable ex vivo up to 13 years after the acute infection. Tetramer analysis further showed that up to 16.8% of all circulating CD3+CD8+ T cells were specific for the single HLA-B*3501-restricted epitope Gn465–473 years after the acute infection. Remarkably, Gn465–473–specific cells readily secreted IFN-γ, granzyme B and TNF-α but not IL-2 upon stimulation and showed a ‘revertant’ CD45RA+CD27−CD28−CCR7−CD127− effector memory phenotype, thereby resembling a phenotype seen in other latent virus infections. Most intriguingly, titers of neutralizing antibodies increased over time in 10/17 individuals months to years after the acute infection and independently of whether they were residents of endemic areas or not. Thus, our data suggest intrinsic, latent antigenic stimulation of Gn-specific T-cells. However, it remains a major task for future studies to proof this hypothesis by determination of viral antigen in convalescent patients. Furthermore, it remains to be seen whether Gn-specific T cells are critical for viral control and protective immunity. If so, Gn-derived immunodominant epitopes could be of high value for future ANDV vaccines

The Role of Interleukin-1 and Interleukin-18 in Pro-Inflammatory and Anti-Viral Responses to Rhinovirus in Primary Bronchial Epithelial Cells

Human Rhinovirus (HRV) is associated with acute exacerbations of chronic respiratory disease. In healthy individuals, innate viral recognition pathways trigger release of molecules with direct anti-viral activities and pro-inflammatory mediators which recruit immune cells to support viral clearance. Interleukin-1alpha (IL-1α), interleukin-1beta (IL-1β) and interleukin-18 (IL-18) have critical roles in the establishment of neutrophilic inflammation, which is commonly seen in airways viral infection and thought to be detrimental in respiratory disease. We therefore investigated the roles of these molecules in HRV infection of primary human epithelial cells. We found that all three cytokines were released from infected epithelia. Release of these cytokines was not dependent on cell death, and only IL-1β and IL-18 release was dependent on caspase-1 catalytic activity. Blockade of IL-1 but not IL-18 signaling inhibited up-regulation of pro-inflammatory mediators and neutrophil chemoattractants but had no effect on virus induced production of interferons and interferon-inducible genes, measured at both mRNA and protein level. Similar level of virus mRNA was detected with and without IL-1RI blockade. Hence IL-1 signaling, potentially involving both IL-1β and IL-1α, downstream of viral recognition plays a key role in induction of pro-inflammatory signals and potentially in recruitment and activation of immune cells in response to viral infection instigated by the epithelial cells, whilst not participating in direct anti-viral responses

Analysis of FOXP3+ Regulatory T Cells That Display Apparent Viral Antigen Specificity during Chronic Hepatitis C Virus Infection

We reported previously that a proportion of natural CD25+ cells isolated from the PBMC of HCV patients can further upregulate CD25 expression in response to HCV peptide stimulation in vitro, and proposed that virus-specific regulatory T cells (Treg) were primed and expanded during the disease. Here we describe epigenetic analysis of the FOXP3 locus in HCV-responsive natural CD25+ cells and show that these cells are not activated conventional T cells expressing FOXP3, but hard-wired Treg with a stable FOXP3 phenotype and function. Of ∼46,000 genes analyzed in genome wide transcription profiling, about 1% were differentially expressed between HCV-responsive Treg, HCV-non-responsive natural CD25+ cells and conventional T cells. Expression profiles, including cell death, activation, proliferation and transcriptional regulation, suggest a survival advantage of HCV-responsive Treg over the other cell populations. Since no Treg-specific activation marker is known, we tested 97 NS3-derived peptides for their ability to elicit CD25 response (assuming it is a surrogate marker), accompanied by high resolution HLA typing of the patients. Some reactive peptides overlapped with previously described effector T cell epitopes. Our data offers new insights into HCV immune evasion and tolerance, and highlights the non-self specific nature of Treg during infection