This open access archive contains publications from University of Arizona faculty, researchers and staff, primarily open-access versions of formally published journal articles. The collection includes published articles and final accepted manuscripts submitted by UA faculty under the UA Open Access Policy. The collection also includes books, book chapters, book reviews, presentations, data, and other scholarly materials submitters have chosen to make available in the repository.

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Recent Submissions

  • Acoustic source localization in non-homogenous plates

    Yin, Shenxin; Cui, Zhiwen; Kundu, Tribikram; Univ Arizona, Dept Civil & Architectural Engn & Mech (SPIE-INT SOC OPTICAL ENGINEERING, 2019-04-01)
    In a nonhomogeneous specimen, if the acoustic source and receiving sensors are located in different media then the acoustic source localization becomes very difficult. In this paper, a recently developed source localization technique is extended to non-homogeneous plates by appropriately considering and modeling the refraction phenomenon. The modified technique is applied to two-layered structure. The proposed new technique gives a relatively simple way to localize the acoustic source without the need to solve a system of nonlinear equations, and thus it avoids the problem of multiplicity, converging to local minima instead of global minimum and giving wrong solution. The proposed technique works for both isotropic and anisotropic structures. The finite element simulation shows that this modified technique considering refraction at material interfaces can localize the acoustic source better than when this modification is not considered.
  • An assessment of in-field non-destructive testing methods for detection of internal defects in standing live trees

    Taskhiri, Mohammad Sadegh; Hafezi, Mohammad Hadi; Holloway, Damien; Turner, Paul; Univ Arizona, Dept Civil Engn & Engn Mech (SPIE-INT SOC OPTICAL ENGINEERING, 2019-04-01)
    Harvesting trees that contain internal defects such as knots and cracks are neither financially nor environmentally sustainable. In hardwood plantations, it is impossible to produce sawlogs from knotty or cracked timber. The challenge is to identify internal defects in a timely and cost-effective manner prior to harvesting. The aim of this paper is to investigate non-destructive testing (NDT) methods to rapidly detect the presence of internal defects in standing live trees in plantation plots. The study highlights that whilst several methods exist, few have been actively applied in-field harvesting operations to optimise log handling and to increase transportation efficiencies. Key constraints are portability of the NDT equipment for use in-field, speed versus accuracy of measurements undertaken and the usability of different evaluation approaches for decision-support. In this paper, the field assessment involved using two non-destructive techniques, ground penetrating radar (GPR) and ultrasonics that use electromagnetic and ultrasonic sound waves respectively to penetrate the internal structure of standing trees. These assessment techniques can assist forest growers to more accurately evaluate the quality of growing stems in the field. They also open the opportunity to investigate differences across a wide selection of growing conditions and forest types to generate data that may support the generation of a software algorithm for predictive imputation of likely internal defect rates within particular forests and under particular growing conditions. The plan being to integrate this predictive imputation software into existing geographical information systems owned by industry partners to enable accurate mapping of land areas where high ratios of defects are likely to be detected to further optimise infield harvesting.
  • Acoustic source localization in anisotropic plates without knowing their material properties: an experimental investigation

    Sen, Novonil; Gawroński, Mateusz; Packo, Pawel; Uhl, Tadeusz; Kundu, Tribikram; Univ Arizona, Dept Civil & Architectural Engn & Mech; Univ Arizona, Dept Aerosp & Mech Engn (SPIE-INT SOC OPTICAL ENGINEERING, 2019-04-01)
    An integral aspect of modern infrastructural engineering is to constantly monitor the health of a structure either actively or passively in order to ensure its safe performance throughout the design life. For passive structural health monitoring, it is important to estimate the location of an acoustic source that may be caused by events such as impact of a foreign object with the structure, failure of a structural element, formation of cracks, etc. Such an acoustic source generates acoustic waves that propagate through the medium. These waves can be captured by ultrasonic sensors mounted on the structure at some pre-selected locations and, subsequently, analyzed to predict the location of the acoustic source. Over the years, several researchers have proposed techniques for acoustic source localization in both isotropic and anisotropic structures. While acoustic source localization in isotropic structures is relatively simple, introduction of anisotropy adds a layer of difficulty to the problem due to the fact that waves do not propagate with the same speed in all directions. This study presents acoustic source localization techniques for anisotropic plates based on the analysis of the wave front shapes typically observed in anisotropic plates and presents experimental verification of the techniques. Three different geometric shapes are considered as the assumed wave front shapes: a rhombus, an ellipse and a parametric curve. A slightly modified version of the rhombus-based technique from the original approach is proposed. The experimental study is performed on two plates with different degrees of anisotropy.
  • Linear and non-linear analysis of composite plates using guided acoustic waves

    Alnuaimi, Hamad; Amjad, Umar; Russo, Pietro; Lopresto, Valentina; Kundu, Tribikram; Univ Arizona, Aerosp & Mech Engn Dept; Univ Arizona, Dept Civil & Architectural Engn & Mech (SPIE-INT SOC OPTICAL ENGINEERING, 2019-04-01)
    Guided acoustic wave techniques have been found to be very effective for damage detection. In this investigation Lead Zirconate Titanate (PZT) transducers are used to generate guided acoustic waves for structural health monitoring of a variety of composite specimens. Multiple sets of composite plate specimens are inspected for impact induced damage detection using PZT transducers. Composite samples are divided into two groups for comparative studies i.e. glass fiber composites and basalt fiber composites. They are damaged by impactors having different levels of impact energy. A chirp signal is excited and propagated through the specimens in a single sided excitation/detection setup to investigate the damages induced by impacts of varying intensity. Signal processing of the recorded signals for damage analysis involved both linear and nonlinear analyses. Linear ultrasonic analysis such as change in the time-of-flight of the propagating waves, Fast Fourier Transform and S-Transform of the recorded signals were tried out while the nonlinear ultrasonic analysis involved the Sideband Peak Count or the SPC technique.
  • In vivo multiphoton imaging of an ovarian cancer mouse model

    Sawyer, Travis W.; Rice, Photini F.; Koevary, Jennifer W.; Barton, Jennifer K.; Connolly, Denise C.; Cai, Kathy Q.; Univ Arizona, Biomed Engn; Univ Arizona, Coll Opt Sci (SPIE-INT SOC OPTICAL ENGINEERING, 2019-02-26)
    Ovarian cancer is the deadliest gynecologic cancer due to predominantly late diagnosis. Early detection of ovarian cancer can increase 5-year survival rates from 40% up to 92%, yet no reliable early detection techniques exist. Multiphoton microscopy (MPM) is a relatively new imaging technique with tremendous potential for clinical diagnosis. A sub-modality of MPM is second harmonic generation (SHG) imaging, which generates contrast from anisotropic structures like collagen molecules, enabling the acquisition of detailed molecular structure maps. As collagen is known to change throughout the progression of cancer, MPM is a promising candidate for ovarian cancer screening. While MPM has shown favorable results in a research environment, it has not yet found broad success in a clinical setting. One major obstacle is the quantitative analysis of the image content. Recently, the application of texture analysis to MPM images has shown success for characterizing the collagen content of the tissue, making it a prime candidate for disease screening. Unfortunately, existing work is limited in its application to ovarian tissue and few texture analysis approaches have been evaluated in this context. To address these challenges, we applied texture analysis to second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) images of a mouse model (TgMISIIR-TAg) of ovarian cancer. Using features from the grey-level co-occurrence matrix, we find that texture analysis of TPEF images of the ovary can differentiate between genotype with high statistical significance (p<0.001), whereas TPEF and SHG images of the oviducts are most sensitive to age, and SHG images of the ovaries are most sensitive to reproductive status. While these results suggest that texture analysis is suitable for characterizing ovarian tissue health, further work is focused on developing a classification algorithm based on these features, and also to couple the results with a histopathological analysis.
  • Searches for scalar leptoquarks and differential cross-section measurements in dilepton-dijet events in proton-proton collisions at a centre-of-mass energy of root s=13TeV with the ATLAS experiment

    Berlendis, S.; Cheu, E.; Johns, K.A.; Jones, S.; Lampl, W.; LeBlanc, M.; Leone, R.; Loch, P.; Nayyar, R.; Varnes, E.W.; et al. (SPRINGER, 2019-09)
    Searches for scalar leptoquarks pair-produced in proton-proton collisions at root s = 13 TeV at the Large Hadron Collider are performed by the ATLAS experiment. A data set corresponding to an integrated luminosity of 36.1 fb(-1) is used. Final states containing two electrons or two muons and two or more jets are studied, as are states with one electron or muon, missing transverse momentum and two or more jets. No statistically significant excess above the Standard Model expectation is observed. The observed and expected lower limits on the leptoquark mass at 95% confidence level extend up to 1.29 TeV and 1.23 TeV for first-and second-generation leptoquarks, respectively, as postulated in the minimal Buchmuller-Ruckl-Wyler model, assuming a branching ratio into a charged lepton and a quark of 50%. In addition, measurements of particle-level fiducial and differential cross sections are presented for the Z -> ee, Z -> mu mu and t (t) over bar processes in several regions related to the search control regions. Predictions from a range of generators are compared with the measurements, and good agreement is seen for many of the observables. However, the predictions for the Z -> ll measurements in observables sensitive to jet energies disagree with the data.
  • Sudden-onset Hypoglycemia Following Fluid Replacement in a Patient with Dapagliflozin-induced Diabetic Ketoacidosis Without Prior Insulin Use: Case Report

    Elshimy, Ghada; Correa, Ricardo; Univ Arizona, Coll Med Phoenix, Endocrinol Diabet & Metab (CUREUS INC, 2019-08-21)
    Euglycemic diabetic ketoacidosis (DKA) is a known complication of sodium-glucose co-transporter 2 (SGLT-2) inhibitors that have been reported in the literature. The prevalence of this side effect is growing and the exact mechanism of action on why this happens is unknown. Hypoglycemia events are very rare in diabetic patients using SGLT-2 inhibitors and/or metformin when they have normal kidney function. We report a novel complication of hypoglycemia that occurred during the course of treatment of SGLT2 inhibitor-induced DKA in a patient with type 2 diabetes mellitus (T2DM) on the dapagliflozin-metformin combination.
  • Simple Reason for Hypoglycemia: ACE Inhibitor-induced Severe Recurrent Hypoglycemia in a Nondiabetic Patient

    Elshimy, Ghada; Techathaveewat, Pawarid; Alsayed, Mahmoud; Jyothinagaram, Sathya; Correa, Ricardo; Univ Arizona, Coll Med Phoenix, Endocrinol Diabet & Metab (CUREUS INC, 2019-08-21)
    Angiotensin-converting enzyme (ACE) inhibitors are among the most common medications used to treat patients with concomitant diabetes and hypertension. They are considered the first line of treatment for hypertension in this population. Several case studies have reported that ACE inhibitors can induce hypoglycemia in patients with diabetes. To our knowledge, however, ACE inhibitors have not been found to induce hypoglycemia in patients without diabetes. This report describes a patient without diabetes experiencing recurrent severe hypoglycemia induced by the ACE inhibitor lisinopril.
  • Parameter Sensitivity Analysis for Computationally Intensive Spatially Distributed Dynamical Environmental Systems Models

    Huo, Xueli; Gupta, Hoshin; Niu, Guo‐Yue; Gong, Wei; Duan, Qingyun; Univ Arizona, Dept Hydrol & Atmospher Sci (AMER GEOPHYSICAL UNION, 2019)
    Dynamical environmental systems models are highly parameterized, having large numbers of parameters whose values are uncertain. For spatially distributed continental-scale applications, such models must be run for very large numbers of grid locations. To calibrate such models, it is useful to be able to perform parameter screening, via sensitivity analysis, to identify the most important parameters. However, since this typically requires the models to be run for a large number of sampled parameter combinations, the computational burden can be huge. To make such an investigation computationally feasible, we propose a novel approach to combining spatial sampling with parameter sampling and test it for the Noah-MP land surface model applied across the continental United States, focusing on gross primary production and flux of latent heat simulations for two vegetation types. Our approach uses (a) progressive Latin hypercube sampling to sample at four grid levels and four parameter levels, (b) a recently developed grouping-based sensitivity analysis approach that ranks parameters by importance group rather than individually, and (c) a measure of robustness to grid and parameter sampling variability. The results show that a relatively small grid sample size (i.e., 5% of the total grids) and small parameter sample size (i.e., 5 times the number of parameters) are sufficient to identify the most important parameters, with very high robustness to grid sampling variability and a medium level of robustness to parameter sampling variability. The results ensure a dramatic reduction in computational costs for such studies.
  • Collaboration, Consultation, or Transaction: Modes of Team Research in Humanities Scholarship and Strategies for Library Engagement

    Senseney, Megan; Koehl, Eleanor; Nay, Leanne; Univ Arizona Lib, Off Digital Innovat & Stewardship (ASSOC COLL RESEARCH LIBRARIES, 2019-09)
    With the rise of digital scholarship, humanists are participating in increasingly complex research teams and partnerships, and academic libraries are developing innovative service models to meet their needs. This paper explores modes of coworking in humanities research by synthesizing responses from two qualitative studies of research practices in the humanities and proposes a taxonomy of multiperson research that includes collaborative, consultative, and transactional research partnerships among scholars, graduate students, academic staff, and a range of other potential stakeholders. Based on an analysis of humanities scholars' self-described research behaviors, we provide recommendations for academic librarians who are developing and sustaining service models for digital scholarship.
  • Competency building for lay health workers is an intangible force driving basic public health services in Southwest China

    Liang, Shengxiang; Deng, Haoyue; Liu, Shili; Wang, Geng; Li, Li; Wang, Mei; Pu, Jie; Xing, Wei; Luo, Xingneng; Ehiri, John; et al. (BMC, 2019-08-23)
    Background: Providing universal basic public health services (BPHS) for residents is the main goal of the new health reform in China. Lay health workers (LHWs) in primary health care (PHC) sectors play key roles in BPHS delivery. The competency of LHWs is critical to quality BPHS. This study assessed LHWs' competency to deliver BPHS and related training in resource-limited Southwest China. Methods: A mixed research method combining in-depth interviews with secondary data collection was used to collect data in this cross-sectional study. Fifty-four LHWs and 16 leaders in 16 PHC sectors were recruited for in-depth interviews. Secondary data on 198 LHWs were collected through standard forms. Results: Both the interviews and secondary data suggested that all PHC sectors did not have sufficient LHWs and lacked qualified LHWs to deliver BPHS overall, particularly in relatively low economic rural areas in Guizhou province. Furthermore, PHC sectors had difficulties retaining existing LHWs due to low incomes and fewer opportunities for self-development. In-depth interviews discovered that, although numerous training opportunities have been provided for LHWs since 2009, the trainings did not achieve the expected outcome in LHW competency building, as LHWs actually did not have access to the trainings and the training design was unresponsive to the actual needs of LHWs. Both LHWs and leaders expressed an urgent need for effective training for LHWs based on systematic needs assessments and the use of qualified trainers and materials. Conclusions: The shortage of qualified LHWs in PHC sectors became the bottleneck for BPHS delivery in Southwest China. Recent trainings for LHWs were less effective with regard to LHW competency building. A need-based professional training programme for LHWs by qualified trainers was expected by both LHWs and leaders in PHC sectors.
  • Impact of changes in home smoking bans on tobacco cessation among quitline callers

    Yuan, Nicole P; Nair, Uma S; Crane, Tracy E; Krupski, Laurie; Collins, Bradley N; Bell, Melanie L; Department of Health Promotion Sciences; Division of Biobehavioral Health Sciences; Department of Epidemiology and Biostatistics (OXFORD UNIV PRESS, 2019-06-01)
    Home smoking bans may be an effective way to promote tobacco cessation among treatment seeking smokers. Few studies have examined this relationship in a quitline setting. Data were obtained from 14,296 adults who were enrolled in a state quitline between January 2011 and July 2016. This study investigated whether cessation rates varied by changes in home smoking ban implementation between enrollment and 7-month follow-up. The impact of changes in home smoking bans on cessation at follow-up was significantly modified by having other smokers living in the home at follow-up (p<0.0001). Among callers who did not live with other smokers in the home, the highest odds ratio of 30-day cessation was for callers who reported bans at follow-up only (OR=10.50, 95%CI: 8.00, 13.70), followed by callers who reported bans at both enrollment and follow-up (OR=8.02, 95%CI: 6.27, 10.30) and callers who reported bans at enrollment only (OR=2.06, 95%CI:1.47, 2.89) compared to callers with no home smoking bans. When callers reported that they lived with other smokers in the home, the effect of home smoking bans on cessation was much smaller. Quitlines should support the implementation of home smoking bans as a part of callers’ goal setting activities to achieve tobacco cessation.
  • Draft Genome Assembly of the Entomopathogenic Bacterium Photorhabdus luminescens subsp. sonorensis Caborca

    Duong, Duy An; Espinosa-Artiles, Patricia; Orozco, Rousel A; Molnár, István; Stock, S Patricia; Univ Arizona, Ctr Insect Sci; Univ Arizona, Southwest Ctr Nat Prod Res; Univ Arizona, Dept Entomol; Univ Arizona, Sch Anim & Comparat Biomed Sci (AMER SOC MICROBIOLOGY, 2019-09)
    Photorhabdus luminescens subsp. sonorensis strain Caborca is an entomopathogenic bacterium with a dual lifestyle, namely, as a mutualist of the Heterorhabditis sonorensis nematode and a pathogen to a wide range of insect species. The genome assembly, in 231 contigs, is 5.2 Mbp long and includes 25 putative gene clusters for secondary metabolism.
  • Explaining the ANITA anomaly with inelastic boosted dark matter

    Heurtier, Lucien; Kim, Doojin; Park, Jong-Chul; Shin, Seodong; Univ Arizona, Dept Phys (AMER PHYSICAL SOC, 2019-09-05)
    We propose a new physics scenario in which the decay of a very heavy dark-matter candidate which does not interact with the neutrino sector could explain the two anomalous events recently reported by the Antarctic Impulsive Transient Antenna Collaboration. The model is composed of two components of dark matter, an unstable dark-sector state and a massive dark gauge boson. We assume that the heavier dark-matter particle of an EeV-range mass is distributed over the Galactic halo and disintegrates into a pair of lighter-highly boosted-dark-matter states in the present Universe which reach and penetrate the Earth. The latter scatters inelastically off a nucleon and produces a heavier dark-sector unstable state which subsequently decays back to the lighter dark matter along with hadrons, which induce extensive air showers, via on /off shell dark gauge boson. Depending on the mass hierarchy within the dark sector, either the dark gauge boson or the unstable dark-sector particle can be long-lived, hence transmitted significantly through the Earth. We study the angular distribution of the signal and show that our model favors emergence angles in the range similar to 25 degrees-35 degrees if the associated parameter choices bear the situation where the mean free path of the boosted incident particle is much larger than the Earth diameter, while its long-lived decay product has a decay length of dimensions comparable to the Earth radius. Our model, in particular, avoids any constraints from complementary neutrino searches such as IceCube or the Auger observatory.
  • Defective Transcriptional Programming of Effector CD8 T Cells in Aged Mice Is Cell-Extrinsic and Can Be Corrected by Administration of IL-12 and IL-18

    Jergović, Mladen; Thompson, Heather L.; Renkema, Kristin R.; Smithey, Megan J.; Nikolich-Žugich, Janko; Univ Arizona, Dept Immunobiol, Coll Med Tucson; Univ Arizona, Ctr Aging, Coll Med Tucson (FRONTIERS MEDIA SA, 2019-09-18)
    In response to infection with intracellular microorganisms, old mice mobilize decreased numbers of antigen-specific CD8T cells with reduced expression of effector molecules and impaired cytolytic activity. Molecular mechanisms behind these defects and the cell-intrinsic (affecting naive CD8 T cells themselves) vs. extrinsic, microenvironmental origin of such defects remain unclear. Using reciprocal transfer experiments of highly purified naive T cells from adult and old transgenic OT-1 mice, we decisively show that the dominant effect is cell-extrinsic. Naive adult OT-1 T cells failed to expand and terminally differentiate in the old organism infected with Listeria-OVA. This defect was preceded by blunted expression of the master transcription factor T-bet and impaired glycolytic switch when T cells are primed in the old organism. However, both old and adult naive CD8T cells proliferated and produced effector molecules to a similar extent when stimulated in vitro with polyclonal stimuli, as well as when transferred into adult recipients. Multiple inflammatory cytokines with direct effects on T cell effector differentiation were decreased in spleens of old animals, particularly IL-12 and IL-18. Of note, in vivo treatment of mice with IL-12 and IL-18 on days 4-6 of Listeria infection reconstituted cytotoxic T cell response of aged mice to the level of adult. Therefore, critical cytokine signals which are underproduced in the old priming environment can restore proper transcriptional programming of old naive CD8T cells and improve immune defense against intracellular microorganisms.
  • Targeting the Non-catalytic RVxF Site of Protein Phosphatase-1 With Small Molecules for Ebola Virus Inhibition

    Lin, Xionghao; Ammosova, Tatiana; Choy, Meng S.; Pietzsch, Colette A.; Ivanov, Andrey; Ahmad, Asrar; Saygideğer, Yasemin; Kumari, Namita; Kovalskyy, Dmytro; Üren, Aykut; et al. (FRONTIERS MEDIA SA, 2019-09-13)
    Ebola virus (EBOV) is a non-segmented negative-sense RNA virus that causes a severe human disease. The ongoing EBOV outbreak in the Eastern part of Democratic Republic of the Congo has resulted to date in over 2500 confirmed cases including over 1500 deaths. Difficulties with vaccine administration indicate the necessity for development of new general drugs and therapeutic strategies against EBOV. Host Ser/Thr protein phosphatases, particularly PP1 and PP2A, facilitate EBOV transcription by dephosphorylating the EBOV VP30 protein and switching activity of the polymerase complex toward replication. Previously, we developed small molecule 1E7-03 that targeted host protein phosphatase-1 (PP1) and induces phosphorylation of EBOV VP30 protein thus shifting transcription-replication balance and inhibiting EBOV replication. Here, we developed a new EBOV inhibitor, 1E7-07, that potently inhibits EBOV replication and displays significantly improved metabolic stability when compared to previously described 1E7-03. Proteome analysis of VP30 shows that 1E7-07 increases its phosphorylation on Thr-119 and Ser-124 over 3-fold with p < 0.001, which likely contributes to EBOV inhibition. We analyzed 1E7-07 binding to PP1 using a mass spectrometry-based protein painting approach. Combined with computational docking, protein painting shows that 1E7-07 binds to several PP1 sites including the RVxF site, C-terminal groove and NIPP1-helix binding pocket. Further analysis using surface plasmon resonance and a split NanoBiT system demonstrates that 1E7-07 binds primarily to the RVxF site. Together, detailed analysis of 1E7-07 binding to PP1 and identification of the RVxF site as the main binding site opens up an opportunity for future development of PP1-targeting EBOV inhibitors.
  • Drivers of C cycling in three arctic-alpine plant communities

    Sørensen, Mia Vedel; Graae, Bente Jessen; Classen, Aimee; Enquist, Brian J.; Strimbeck, Richard; Univ Arizona, Dept Ecol & Evolutionary Biol, BioSci West (TAYLOR & FRANCIS LTD, 2019)
    Recent vegetation changes in arctic-alpine tundra ecosystems may affect several ecosystem processes that regulate microbe and soil functions. Such changes can alter ecosystem carbon (C) cycling with positive feedback to the atmosphere if plant C uptake is less than the amount of soil C released. Here, we examine how differences in plant functional traits, microbial activity, and soil processes within and across Salix-dominated shrub, dwarf shrub-dominated heath, and herb- and cryptogam-dominated meadow communities influence C cycling. We develop a hypothesized framework based on a priori model selection of variation in daytime growing season gross ecosystem photosynthesis (GEP) and above-and belowground respiration. The fluxes were standardized to light and temperature. Gross ecosystem photosynthesis was primarily related to soil moisture and secondarily to plant functional traits and aboveground biomass, and belowground respiration was dependent on the community weighted mean of specific leaf area (SLA(CWM)). Similarly, microbial activity was linked with SLA(CWM) and was highest in meadows, and carbon-degrading microbial activity decreased with vegetation woodiness. These results suggest that shrub expansion may influence summer C cycling differently depending on plant community, as belowground respiration might increase in the heath and decrease in the meadow communities.
  • Inheritance of HLA-Cw7 Associated With Autism Spectrum Disorder (ASD)

    Harville, Terry; Rhodes-Clark, Bobbie; Bennuri, Sirish C.; Delhey, Leanna; Slattery, John; Tippett, Marie; Wynne, Rebecca; Rose, Shannon; Kahler, Stephen; Frye, Richard E.; et al. (FRONTIERS MEDIA SA, 2019-09-11)
    Autism spectrum disorder (ASD) is a behaviorally defined disorder that is now thought to affect approximately 1 in 69 children in the United States. In most cases, the etiology is unknown, but several studies point to the interaction of genetic predisposition with environmental factors. The immune system is thought to have a causative role in ASD, and specific studies have implicated T lymphocytes, monocytes, natural killer (NK) cells, and certain cytokines. The human leukocyte antigen (HLA) system is involved in the underlying process for shaping an individual's immune system, and specific HLA alleles are associated with specific diseases as risk factors. In this study, we determine whether a specific HLA allele was associated with ASD in a large cohort of patients with ASD. Identifying such an association could help in the identification of immune system components which may have a causative role in specific cohorts of patients with ASD who share similar specific clinical features. Specimens from 143 patients with ASD were analyzed with respect to race and ethnicity. Overall, HLA-Cw7 was present in a much greater frequency than expected in individuals with ASD as compared to the general population. Further, the cohort of patients who express HLA-Cw7 shares specific immune system/inflammatory clinical features including being more likely to have allergies, food intolerances, and chronic sinusitis as compared to those with ASD who did not express HLA-Cw7. HLA-Cw7 has a role in stimulating NK cells. Thus, this finding may indicate that chronic over-activation of NK cells may have a role in the manifestation of ASD in a cohort of patients with increased immune system/inflammatory features.
  • Secondary Aortoduodenal Fistula Presenting as Gastrointestinal Bleeding and Fungemia

    Vegunta, Radhakrishna; Vegunta, Rathnamitreyee; Kutti Sridharan, Gurusaravanan; Univ Arizona, Internal Med (CUREUS INC, 2019-09-05)
    A 55-year-old African American man with a history of abdominal aortic pseudoaneurysm repair presented to the ED with complaints of black-colored stools mixed with fresh blood and fever for three days duration. The exam was unremarkable except for abdominal bruits and pallor. CT angiogram showed perigraft fluid collection, bowel wall thickening, and loss of normal fat planes between the aorta and adjacent bowel at the level of the third portion of the duodenum. Polymicrobial infection was noted in the aortic graft and blood cultures grew Candida. The patient underwent urgent removal of the infected graft, duodenal repair along with appropriate antimicrobial therapy. He did well postoperatively and was discharged in a stable condition. Our case highlights the importance of maintaining a high index of suspicion of aortoenteric fistula (AEF) when a patient with a prior abdominal aortic graft develops gastrointestinal (GI) bleeding as this condition is universally fatal if unrecognized.
  • Hypoxia-induced PIM kinase and laminin-activated integrin alpha 6 mediate resistance to PI3K inhibitors in bone-metastatic CRPC

    Toth, Rachel K; Tran, Jack D; Muldong, Michelle T; Nollet, Eric A; Schulz, Veronique V; Jensen, Corbin C; Hazlehurst, Lori A; Corey, Eva; Durden, Donald; Jamieson, Christina; et al. (E-CENTURY PUBLISHING CORP, 2019)
    Bone-metastatic castration-resistant prostate cancer (CRPC) is lethal due to inherent resistance to androgen deprivation therapy, chemotherapy, and targeted therapies. Despite the fact that a majority of CRPC patients (approximately 70%) harbor a constitutively active PI3K survival pathway, targeting the PI3K/mTOR pathway has failed to increase overall survival in clinical trials. Here, we identified two separate and independent survival pathways induced by the bone tumor microenvironment that are hyperactivated in CRPC and confer resistance to PI3K inhibitors. The first pathway involves integrin α6β1-mediated adhesion to laminin and the second involves hypoxia-induced expression of PIM kinases. In vitro and in vivo models demonstrate that these pathways transduce parallel but independent signals that promote survival by reducing oxidative stress and preventing cell death. We further demonstrate that both pathways drive resistance to PI3K inhibitors in PTEN-negative tumors. These results provide preclinical evidence that combined inhibition of integrin α6β1 and PIM kinase in CRPC is required to overcome tumor microenvironment-mediated resistance to PI3K inhibitors in PTEN-negative tumors within the hypoxic and laminin-rich bone microenvironment.

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