30 results on '"Fisher, Cynthia"'
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2. Apples to apples: The challenges of studying COVID-19 mortality in solid organ transplant recipients.
- Author
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Heldman MR, Rakita RM, Lease ED, Fisher CE, and Limaye AP
- Subjects
- Humans, SARS-CoV-2, Transplant Recipients, COVID-19, Malus, Organ Transplantation
- Published
- 2022
- Full Text
- View/download PDF
3. Changing trends in mortality among solid organ transplant recipients hospitalized for COVID-19 during the course of the pandemic.
- Author
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Heldman MR, Kates OS, Safa K, Kotton CN, Georgia SJ, Steinbrink JM, Alexander BD, Hemmersbach-Miller M, Blumberg EA, Multani A, Haydel B, La Hoz RM, Moni L, Condor Y, Flores S, Munoz CG, Guitierrez J, Diaz EI, Diaz D, Vianna R, Guerra G, Loebe M, Rakita RM, Malinis M, Azar MM, Hemmige V, McCort ME, Chaudhry ZS, Singh PP, Hughes Kramer K, Velioglu A, Yabu JM, Morillis JA, Mehta SA, Tanna SD, Ison MG, Derenge AC, van Duin D, Maximin A, Gilbert C, Goldman JD, Lease ED, Fisher CE, and Limaye AP
- Subjects
- Humans, Pandemics, SARS-CoV-2, Transplant Recipients, COVID-19, Organ Transplantation adverse effects
- Abstract
Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46-0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2022
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4. COVID-19 in hospitalized lung and non-lung solid organ transplant recipients: A comparative analysis from a multicenter study.
- Author
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Heldman MR, Kates OS, Safa K, Kotton CN, Georgia SJ, Steinbrink JM, Alexander BD, Hemmersbach-Miller M, Blumberg EA, Crespo MM, Multani A, Lewis AV, Eugene Beaird O, Haydel B, La Hoz RM, Moni L, Condor Y, Flores S, Munoz CG, Guitierrez J, Diaz EI, Diaz D, Vianna R, Guerra G, Loebe M, Rakita RM, Malinis M, Azar MM, Hemmige V, McCort ME, Chaudhry ZS, Singh P, Hughes K, Velioglu A, Yabu JM, Morillis JA, Mehta SA, Tanna SD, Ison MG, Tomic R, Candace Derenge A, van Duin D, Maximin A, Gilbert C, Goldman JD, Sehgal S, Weisshaar D, Girgis RE, Nelson J, Lease ED, Limaye AP, and Fisher CE
- Subjects
- Adult, Aged, Cohort Studies, Humans, Lung, SARS-CoV-2, Transplant Recipients, COVID-19, Organ Transplantation adverse effects
- Abstract
Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID-19) may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID-19 to compare mortality by 28 days between hospitalized LTR and non-lung SOTR. Multivariable logistic regression models were used to assess comorbidity-adjusted mortality among LTR vs. non-lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with COVID-19, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non-lung SOTR (p = .02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p = .032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0-2.6, p = .04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0-11.3, p = .05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID-19, LTR had higher mortality than non-lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2021
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5. The dynamicity of acute ozone-induced systemic leukocyte trafficking and adrenal-derived stress hormones.
- Author
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Henriquez AR, Williams W, Snow SJ, Schladweiler MC, Fisher C, Hargrove MM, Alewel D, Colonna C, Gavett SH, Miller CN, and Kodavanti UP
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- Animals, Apoptosis drug effects, Cytokines metabolism, Gene Expression Regulation, Granulocytes drug effects, Lung metabolism, Lymphocytes drug effects, Male, Monocytes drug effects, Rats, Rats, Inbred WKY, Spleen cytology, Spleen drug effects, T-Lymphocytes, Adrenal Cortex Hormones metabolism, Air Pollutants toxicity, Air Pollution adverse effects, Leukocytes drug effects, Ozone toxicity
- Abstract
Ozone exposure induces neuroendocrine stress response, which causes lymphopenia. It was hypothesized that ozone-induced increases in stress hormones will temporally follow changes in circulating granulocytes, monocytes- and lymphocyte subpopulations. The goal of this study was to chronicle the changes in circulating stress hormones, cytokines, and leukocyte trafficking during 4 h exposure to ozone. Male Wistar Kyoto rats were exposed to air or ozone (0.4 or 0.8 ppm) for 0.5, 1, 2, or 4 h. After each time point, circulating stress hormones, cytokines, and lung gene expression were assessed along with live and apoptotic granulocytes, monocytes (classical and non-classical), and lymphocytes (B, T
h , and Tc ) in blood, thymus, and spleen using flow cytometry. Circulating stress hormones began to increase at 1 h of ozone exposure. Lung expression of inflammatory cytokines (Cxcl2, Il6, and Hmox1) and glucocorticoid-responsive genes (Nr3c1, Fkbp5 and Tsc22d3) increased in both a time- and ozone concentration-dependent manner. Circulating granulocytes increased at 0.5 h of ozone exposure but tended to decrease at 2 and 4 h, suggesting a rapid egress and then margination to the lung. Classical monocytes decreased over 4 h of exposure periods (∼80 % at 0.8 ppm). B and Tc lymphocytes significantly decreased after ozone exposure at 2 and 4 h. Despite dynamic shifts in circulating immune cell populations, few differences were measured in serum cytokines. Ozone neither increased apoptotic cells nor altered thymus and spleen lymphocytes. The data show that ozone-induced increases in adrenal-derived stress hormones precede the dynamic migration of circulating immune cells, likely to the lung to mediate inflammation., (Published by Elsevier B.V.)- Published
- 2021
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6. How do the object-file and physical-reasoning systems interact? Evidence from priming effects with object arrays or novel labels.
- Author
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Lin Y, Li J, Gertner Y, Ng W, Fisher CL, and Baillargeon R
- Subjects
- Attention, Humans, Infant, Knowledge, Problem Solving, Child Development, Cognition
- Abstract
How do infants reason about simple physical events such as containment, tube, and support events? According to the two-system model, two cognitive systems, the object-file (OF) and physical-reasoning (PR) systems, work together to guide infants' responses to these events. When an event begins, the OF system sends categorical information about the objects and their arrangements to the PR system. This system then categorizes the event, assigns event roles to the objects, and taps the OF system for information about features previously identified as causally relevant for the event category selected. All of the categorical and featural information included in the event's representation is interpreted by the PR system's domain knowledge, which includes core principles such as persistence and gravity. The present research tested a novel prediction of the model: If the OF system could be primed to also send, at the beginning of an event, information about an as-yet-unidentified feature, the PR system would then interpret this information using its core principles, allowing infants to detect core violations involving the feature earlier than they normally would. We examined this prediction using two types of priming manipulations directed at the OF system, object arrays and novel labels. In six experiments, infants aged 7-13 months (N = 304) were tested using different event categories and as-yet-unidentified features (color in containment events, height in tube events, and proportional distribution in support events) as well as different tasks (violation-of-expectation and action tasks). In each case, infants who were effectively primed reasoned successfully about the as-yet-unidentified feature, sometimes as early as six months before they would typically do so. These converging results provide strong support for the two-system model and for the claim that uncovering how the OF and PR systems represent and exchange information is essential for understanding how infants respond to physical events., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
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7. Circulating exosomes with lung self-antigens as a biomarker for chronic lung allograft dysfunction: A retrospective analysis.
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Sharma M, Gunasekaran M, Ravichandran R, Fisher CE, Limaye AP, Hu C, McDyer J, Kaza V, Bharat A, Tokman S, Omar A, Arjuna A, Walia R, Bremner RM, Smith MA, Hachem RR, and Mohanakumar T
- Subjects
- Allografts, Biomarkers blood, Bronchiolitis Obliterans surgery, Chronic Disease, Female, Humans, Male, Middle Aged, Primary Graft Dysfunction immunology, Retrospective Studies, Autoantigens blood, Exosomes metabolism, Lung Transplantation adverse effects, Primary Graft Dysfunction blood, Tissue Donors, Transplant Recipients
- Abstract
Background: Exosomes isolated from plasma of lung transplant recipients (LTxRs) with bronchiolitis obliterans syndrome (BOS) contain human leukocyte antigens and lung self-antigens (SAgs), K-alpha 1 tubulin (Kα1T) and collagen type V (Col-V). The aim was to determine the use of circulating exosomes with lung SAgs as a biomarker for BOS., Methods: Circulating exosomes were isolated retrospectively from plasma from LTxRs at diagnosis of BOS and at 6 and 12 months before the diagnosis (n = 41) and from stable time-matched controls (n = 30) at 2 transplant centers by ultracentrifugation. Exosomes were validated using Nanosight, and lung SAgs (Kα1T and Col-V) were detected by immunoblot and semiquantitated using ImageJ software., Results: Circulating exosomes from BOS and stable LTxRs demonstrated 61- to 181-nm vesicles with markers Alix and CD9. Exosomes from LTxRs with BOS (n = 21) showed increased levels of lung SAgs compared with stable (n = 10). A validation study using 2 separate cohorts of LTxRs with BOS and stable time-matched controls from 2 centers also demonstrated significantly increased lung SAgs-containing exosomes at 6 and 12 months before BOS., Conclusions: Circulating exosomes isolated from LTxRs with BOS demonstrated increased levels of lung SAgs (Kα1T and Col-V) 12 months before the diagnosis (100% specificity and 90% sensitivity), indicating that circulating exosomes with lung SAgs can be used as a non-invasive biomarker for identifying LTxRs at risk for BOS., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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8. Emerging evidence to support not always "just saying no" to SARS-CoV-2 positive donors.
- Author
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Kates OS, Fisher CE, Rakita RM, Reyes JD, and Limaye AP
- Subjects
- COVID-19 epidemiology, Humans, Pandemics, COVID-19 transmission, DNA, Viral analysis, Disease Transmission, Infectious prevention & control, Organ Transplantation methods, SARS-CoV-2 genetics, Tissue Donors, Tissue and Organ Procurement methods
- Published
- 2020
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9. Earliest cases of coronavirus disease 2019 (COVID-19) identified in solid organ transplant recipients in the United States.
- Author
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Kates OS, Fisher CE, Stankiewicz-Karita HC, Shepherd AK, Church EC, Kapnadak SG, Lease ED, Riedo FX, Rakita RM, and Limaye AP
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- Aged, COVID-19, Coronavirus Infections diagnosis, Coronavirus Infections therapy, End Stage Liver Disease complications, End Stage Liver Disease surgery, Female, Heart Failure complications, Heart Failure surgery, Heart Transplantation, Hospitalization, Humans, Immunosuppression Therapy adverse effects, Kidney Failure, Chronic complications, Kidney Failure, Chronic surgery, Kidney Transplantation, Liver Transplantation, Lung Diseases complications, Lung Diseases surgery, Lung Transplantation, Male, Middle Aged, Outpatients, Pandemics, Pneumonia, Viral diagnosis, Pneumonia, Viral therapy, United States epidemiology, Vulnerable Populations, Washington, Coronavirus Infections complications, Immunosuppression Therapy methods, Pneumonia, Viral complications, Transplant Recipients
- Abstract
With the rapidly expanding pandemic of SARS-CoV-2, there is concern that solid organ transplant recipients will be particularly vulnerable to infection and may experience a more severe clinical course. We report four cases of COVID-19 in solid organ transplant recipients including recipients of kidney, liver, lung, and heart transplants. We describe each patient's medical history including transplantation history, their clinical presentation and workup, and their course from diagnosis to either hospital discharge or to improvement in symptoms. These reports demonstrate a range of symptoms, clinical severity, and disease course in solid organ transplant recipients with COVID-19, including two hospitalized patients and two patients managed entirely in the outpatient setting., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2020
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10. Use of SARS-CoV-2-infected deceased organ donors: Should we always "just say no?"
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Kates OS, Fisher CE, Rakita RM, Reyes JD, and Limaye AP
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- Betacoronavirus, COVID-19, Ethics, Medical, Heart virology, Heart Transplantation adverse effects, Heart Transplantation trends, Humans, Liver virology, Liver Transplantation adverse effects, Liver Transplantation trends, Lung virology, Occupational Exposure, SARS-CoV-2, Severe Acute Respiratory Syndrome prevention & control, Tissue and Organ Procurement ethics, Waiting Lists, Coronavirus Infections prevention & control, Coronavirus Infections transmission, Pandemics prevention & control, Pneumonia, Viral prevention & control, Pneumonia, Viral transmission, Tissue Donors, Tissue and Organ Procurement standards, Tissue and Organ Procurement trends
- Abstract
In the context of a rapidly evolving pandemic, multiple organizations have released guidelines stating that all organs from potential deceased donors with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection should be deferred, including from otherwise medically eligible donors found to have mild or asymptomatic SARS-CoV-2 discovered on routine donor screening. In this article, we critically examine the available data on the risk of transmission of SARS-CoV-2 through organ transplantation. The isolation of SARS-CoV-2 from nonlung clinical specimens, the detection of SARS-CoV-2 in autopsy specimens, previous experience with the related coronaviruses SARS-CoV and MERS-CoV, and the vast experience with other common RNA respiratory viruses are all addressed. Taken together, these data provide little evidence to suggest the presence of intact transmissible SARS-CoV in organs that can potentially be transplanted, specifically liver and heart. Other considerations including ethical, financial, societal, and logistical concerns are also addressed. We conclude that, for selected patients with high waitlist mortality, transplant programs should consider accepting heart or liver transplants from deceased donors with SARS-CoV-2 infection., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2020
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11. Respiratory viral infection in lung transplantation induces exosomes that trigger chronic rejection.
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Gunasekaran M, Bansal S, Ravichandran R, Sharma M, Perincheri S, Rodriguez F, Hachem R, Fisher CE, Limaye AP, Omar A, Smith MA, Bremner RM, and Mohanakumar T
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- Aged, Animals, Antigens, Viral metabolism, Autoantigens metabolism, Case-Control Studies, Female, HLA Antigens metabolism, Humans, Male, Mice, Mice, Inbred C57BL, Middle Aged, Proteasome Endopeptidase Complex metabolism, Respiratory Tract Infections complications, Respiratory Tract Infections virology, Virus Diseases complications, Exosomes metabolism, Graft Rejection etiology, Graft Rejection metabolism, Lung Transplantation adverse effects, Respiratory Tract Infections metabolism, Virus Diseases metabolism
- Abstract
Background: Respiratory viral infections can increase the risk of chronic lung allograft dysfunction after lung transplantation, but the mechanisms are unknown. In this study, we determined whether symptomatic respiratory viral infections after lung transplantation induce circulating exosomes that contain lung-associated self-antigens and assessed whether these exosomes activate immune responses to self-antigens., Methods: Serum samples were collected from lung transplant recipients with symptomatic lower- and upper-tract respiratory viral infections and from non-symptomatic stable recipients. Exosomes were isolated via ultracentrifugation; purity was determined using sucrose cushion; and presence of lung self-antigens, 20S proteasome, and viral antigens for rhinovirus, coronavirus, and respiratory syncytial virus were determined using immunoblot. Mice were immunized with circulating exosomes from each group and resulting differential immune responses and lung histology were analyzed., Results: Exosomes containing self-antigens, 20S proteasome, and viral antigens were detected at significantly higher levels (p < 0.05) in serum of recipients with symptomatic respiratory viral infections (n = 35) as compared with stable controls (n = 32). Mice immunized with exosomes from recipients with respiratory viral infections developed immune responses to self-antigens, fibrosis, small airway occlusion, and significant cellular infiltration; mice immunized with exosomes from controls did not (p < 0.05)., Conclusions: Circulating exosomes isolated from lung transplant recipients diagnosed with respiratory viral infections contained lung self-antigens, viral antigens, and 20S proteasome and elicited immune responses to lung self-antigens that resulted in development of chronic lung allograft dysfunction in immunized mice., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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12. Gynecologic cancers and solid organ transplantation.
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Liao JB, Fisher CE, and Madeleine MM
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- Female, Genital Neoplasms, Female epidemiology, Humans, Immunosuppressive Agents adverse effects, Neoplasm Recurrence, Local, Papillomavirus Infections epidemiology, Risk, Risk Factors, Tissue Donors, Treatment Outcome, Uterus transplantation, Genital Neoplasms, Female complications, Organ Transplantation adverse effects, Papillomavirus Infections complications
- Abstract
Solid organ transplant (SOT) recipients have an approximately 2-fold greater risk of developing and dying from a malignancy compared to the general population. Among the gynecologic cancers, including uterine, cervical, vaginal, vulvar, and ovarian, the HPV-related cancers are known to increase among women posttransplant compared to women in the general population, but less is known about the risk of uterine and ovarian cancers. This review provides an overview of the epidemiology of gynecologic cancers after solid organ transplantation, as well as the pathophysiology, management, and specific risk factors associated with these cancers. Closer surveillance for cervical cancers is warranted and larger studies are needed to assess whether and how uterine and ovarian cancers are associated with excess incidence and mortality. Such studies may lead to improvements in screening, prevention, and treatment before and after transplantation., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2019
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13. Transplant tourism complicated by life-threatening New Delhi metallo-β-lactamase-1 infection.
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Stewart J, Snoeyenbos Newman G, Jain R, Bryan A, Berger H, Montenovo M, Bakthavatsalam R, Kling CE, Sibulesky L, Shalhub S, Limaye AP, Fisher CE, and Rakita RM
- Subjects
- Anti-Infective Agents administration & dosage, Bacterial Infections drug therapy, Bacterial Infections microbiology, Humans, Male, Middle Aged, Mycoses microbiology, Bacterial Infections complications, Enterobacter cloacae enzymology, Kidney Transplantation, Medical Tourism, Mycoses complications, Rhizopus enzymology, beta-Lactamases isolation & purification
- Abstract
Transplant tourism, which is the practice of traveling to other countries for transplant, continues to be a major problem worldwide. We describe a patient who traveled to Pakistan and underwent commercial kidney transplant. He developed life-threatening infections from New Delhi metallo-β-lactamase-1-producing Enterobacter cloacae and Rhizopus oryzae, resulting in a necrotizing kidney allograft infection and subsequent external iliac artery rupture. He survived after a prolonged course of nonstandardized antimicrobial therapy, including a combination of aztreonam and ceftazidime-avibactam, and aggressive surgical debridement with allograft nephrectomy. The early timing of infection with these unusual organisms localized to the allograft suggests contamination and substandard care at the time of transplant. This case highlights the challenges of caring for these infections and serves as a cautionary tale for the potential complications of commercial transplant tourism., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2019
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14. Interrater agreement in the diagnosis of chronic lung allograft dysfunction after lung transplantation.
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Fisher CE, Kapnadak SG, Lease ED, Edelman JD, and Limaye AP
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- Chronic Disease, Humans, Observer Variation, Retrospective Studies, Lung Transplantation, Postoperative Complications diagnosis, Postoperative Complications physiopathology
- Published
- 2019
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15. Mistakes weren't made: Three-year-olds' comprehension of novel-verb passives provides evidence for early abstract syntax.
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Messenger K and Fisher C
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- Child, Preschool, Female, Humans, Language Development, Male, Semantics, Vocabulary, Comprehension, Linguistics
- Abstract
By about age three, English-learning children begin to understand passive sentences with familiar verbs. We probed the nature of children's linguistic representations by asking whether 3-year-olds promptly extend their emerging knowledge of the passive structure to novel verbs. In three preferential-looking experiments, 3-year-olds (N = 124) interpreted novel verbs presented in short passives (Experiment 1, "She's getting snedded!") as transitive verbs, referring to causal-action rather than solo-action events, and used word-order in full passives, (Experiments 2 and 3, e.g., "She's getting snedded by the boy!"), to select a target event in which the subject was the patient, not the agent of action. Comprehension accuracy in Experiments 1 and 2 varied with vocabulary, but this vocabulary effect disappeared when children were given more time and more repetitions of the test sentences (Experiment 3). These findings support early-abstraction accounts of acquisition: 3-year-olds represent passive syntax in abstract terms, permitting extension to novel verbs. This, in turn, allows them to use passive sentences to identify the grammatical subcategory and meaning of an unknown verb., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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16. Validation of single nucleotide polymorphisms in invasive aspergillosis following hematopoietic cell transplantation.
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Fisher CE, Hohl TM, Fan W, Storer BE, Levine DM, Zhao LP, Martin PJ, Warren EH, Boeckh M, and Hansen JA
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- Adult, C-Reactive Protein genetics, Cohort Studies, Female, Genetic Predisposition to Disease, Genotype, Humans, Lectins, C-Type genetics, Male, Middle Aged, Serum Amyloid P-Component genetics, Aspergillosis etiology, Aspergillosis genetics, Hematopoietic Stem Cell Transplantation adverse effects, Polymorphism, Single Nucleotide
- Abstract
Invasive aspergillosis (IA) is a significant cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Previous studies have reported an association between IA development and single nucleotide polymorphisms (SNPs), but many SNPs have not been replicated in a separate cohort. The presence of a positive serum galactomannan assay (SGM+) has also been associated with a worse prognosis in patients with IA, and genetic determinants in this subset of patients have not been systematically studied. The study cohort included 2609 HCT recipients and their donor pairs: 483 with proven/probable IA (183 SGM+) and 2126 with no IA by standard criteria. Of 25 SNPs previously published, we analyzed 20 in 14 genes that passed quality control. Samples were genotyped via microarray, and SNPs that could not be genotyped were imputed. The primary aim was to replicate SNPs associated with proven/probable IA at 2 years; secondary goals were to explore the associations using an end point of SGM+ IA or proven/probable IA using a different genetic model or time to IA (3 months vs 2 years) compared with the original study. Two SNPs in 2 genes ( PTX3 , CLEC7a ) were replicated. Thirteen SNPs in 9 genes had an association at P ≤ .05 using the secondary aims ( PTX3 , CLEC7a , CD209 , CXCL10 , TLR6 , S100B , IFNG , PLG , TNFR1 ), with hazard ratios ranging from 1.2 to 3.29. Underlying genetic differences can influence development of IA following HCT. Identification of genetic predispositions to IA could have important implications in donor screening, risk stratification of recipients, monitoring, and prophylaxis., (© 2017 by The American Society of Hematology.)
- Published
- 2017
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17. Respiratory virus infections and chronic lung allograft dysfunction: Assessment of virology determinants.
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Fisher CE, Mohanakumar T, and Limaye AP
- Subjects
- Lung, Lung Transplantation, Respiratory Tract Infections, Allografts, Transplantation, Homologous
- Published
- 2016
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18. Where are the cookies? Two- and three-year-olds use number-marked verbs to anticipate upcoming nouns.
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Lukyanenko C and Fisher C
- Subjects
- Adolescent, Adult, Child, Preschool, Female, Humans, Male, Young Adult, Anticipation, Psychological physiology, Child Development physiology, Comprehension physiology, Language
- Abstract
We tested toddlers' and adults' predictive use of English subject-verb agreement. Participants saw pairs of pictures differing in number and kind (e.g., one apple, two cookies), and heard sentences with a target noun naming one of the pictures. The target noun was the subject of a preceding agreeing verb in informative trials (e.g., Wherearethe good cookies?), but not in uninformative trials (Do you see the good cookies?). In Experiment 1, 3-year-olds and adults were faster and more likely to shift their gaze from distractor to target upon hearing an informative agreeing verb. In Experiment 2, 2.5-year-olds were faster to shift their gaze from distractor to target in response to the noun in informative trials, and were more likely to be fixating the target already at noun onset. Thus, toddlers used agreeing verbs to predict number features of an upcoming noun. These data provide strong new evidence for the broad scope of predictive processing in online language comprehension., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2016
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19. Idiopathic pneumonia syndrome after hematopoietic cell transplantation: evidence of occult infectious etiologies.
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Seo S, Renaud C, Kuypers JM, Chiu CY, Huang ML, Samayoa E, Xie H, Yu G, Fisher CE, Gooley TA, Miller S, Hackman RC, Myerson D, Sedlak RH, Kim YJ, Fukuda T, Fredricks DN, Madtes DK, Jerome KR, and Boeckh M
- Subjects
- Adolescent, Adult, Aspergillosis diagnosis, Aspergillosis etiology, Aspergillosis microbiology, Aspergillus isolation & purification, Bacterial Infections diagnosis, Bacterial Infections etiology, Bacterial Infections microbiology, Bronchoalveolar Lavage Fluid microbiology, Bronchoalveolar Lavage Fluid virology, Child, Cohort Studies, Female, Humans, Lung microbiology, Lung virology, Lung Injury etiology, Male, Middle Aged, Virus Diseases diagnosis, Virus Diseases etiology, Virus Diseases virology, Young Adult, Hematopoietic Stem Cell Transplantation adverse effects, Lung Injury microbiology, Lung Injury virology
- Abstract
Newer diagnostic methods may link more idiopathic pneumonia syndrome (IPS) cases to an infectious agent. Bronchoalveolar lavage (BAL) samples from 69 hematopoietic cell transplant (HCT) recipients with IPS diagnosed between 1992 and 2006 were tested for 28 pathogens (3 bacteria and 25 viruses) by quantitative polymerase chain reaction and for Aspergillus by galactomannan assay. Research BALs from 21 asymptomatic HCT patients served as controls. Among 69 HCT patients with IPS, 39 (56.5%) had a pathogen detected. The most frequent pathogens were human herpesvirus-6 (HHV-6) (N = 20 [29%]) followed by human rhinovirus (HRV), cytomegalovirus (CMV), and Aspergillus (N = 8 [12%] in each). HHV-6 and HRV were rarely detected in controls, whereas CMV and Aspergillus were occasionally detected with low pathogen load. Patients with pathogens had worse day-100 survival than those without (hazard ratio, 1.88; P = .03). Mortality in patients with only pathogens of "uncertain" significance in lung was similar to that in patients with pathogens of "established" significance. Metagenomic next-generation sequencing did not reveal additional significant pathogens. Our study demonstrated that approximately half of patients with IPS had pathogens detected in BAL, and pathogen detection was associated with increased mortality. Thus, an expanded infection detection panel can significantly increase the diagnostic precision for idiopathic pneumonia., (© 2015 by The American Society of Hematology.)
- Published
- 2015
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20. Predicted errors in children's early sentence comprehension.
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Gertner Y and Fisher C
- Subjects
- Analysis of Variance, Female, Humans, Infant, Language Development, Linguistics, Male, Child Language, Comprehension, Semantics, Vocabulary
- Abstract
Children use syntax to interpret sentences and learn verbs; this is syntactic bootstrapping. The structure-mapping account of early syntactic bootstrapping proposes that a partial representation of sentence structure, the set of nouns occurring with the verb, guides initial interpretation and provides an abstract format for new learning. This account predicts early successes, but also telltale errors: Toddlers should be unable to tell transitive sentences from other sentences containing two nouns. In testing this prediction, we capitalized on evidence that 21-month-olds use what they have learned about noun order in English sentences to understand new transitive verbs. In two experiments, 21-month-olds applied this noun-order knowledge to two-noun intransitive sentences, mistakenly assigning different interpretations to "The boy and the girl are gorping!" and "The girl and the boy are gorping!". This suggests that toddlers exploit partial representations of sentence structure to guide sentence interpretation; these sparse representations are useful, but error-prone., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2012
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21. 2.5-year-olds use cross-situational consistency to learn verbs under referential uncertainty.
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Scott RM and Fisher C
- Subjects
- Child, Preschool, Female, Humans, Male, Vocabulary, Concept Formation, Language, Language Development, Uncertainty
- Abstract
Recent evidence shows that children can use cross-situational statistics to learn new object labels under referential ambiguity (e.g., Smith & Yu, 2008). Such evidence has been interpreted as support for proposals that statistical information about word-referent co-occurrence plays a powerful role in word learning. But object labels represent only a fraction of the vocabulary children acquire, and arguably represent the simplest case of word learning based on observations of world scenes. Here we extended the study of cross-situational word learning to a new segment of the vocabulary, action verbs, to permit a stronger test of the role of statistical information in word learning. In two experiments, on each trial 2.5-year-olds encountered two novel intransitive (e.g., "She's pimming!"; Experiment 1) or transitive verbs (e.g., "She's pimming her toy!"; Experiment 2) while viewing two action events. The consistency with which each verb accompanied each action provided the only source of information about the intended referent of each verb. The 2.5-year-olds used cross-situational consistency in verb learning, but also showed significant limits on their ability to do so as the sentences and scenes became slightly more complex. These findings help to define the role of cross-situational observation in word learning., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2012
- Full Text
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22. Chromatin states in pluripotent, differentiated, and reprogrammed cells.
- Author
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Fisher CL and Fisher AG
- Subjects
- Animals, Gene Regulatory Networks, Humans, Pluripotent Stem Cells cytology, Cell Differentiation, Cellular Reprogramming, Chromatin, Pluripotent Stem Cells metabolism
- Abstract
The pluripotent state of embryonic stem cells is maintained by a core network of transcription factors, and by chromatin remodelling factors that support an environment permissive for transcription. Polycomb and trithorax Group proteins enable 'bivalent' chromatin to be established at lineage-specific genes within pluripotent cells that is thought to poise genes for rapid activation upon induction of differentiation. As differentiation proceeds, chromatin condenses and there is a genome-wide increase in the abundance of repressive histone modifications, alterations in the subnuclear organisation of particular genomic regions, and changes in DNA methylation profiles within genes. Reprogramming of somatic cells provides a platform to investigate the role of chromatin-based factors in establishing and maintaining pluripotency., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
23. Loss-of-function Additional sex combs like 1 mutations disrupt hematopoiesis but do not cause severe myelodysplasia or leukemia.
- Author
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Fisher CL, Pineault N, Brookes C, Helgason CD, Ohta H, Bodner C, Hess JL, Humphries RK, and Brock HW
- Subjects
- Animals, B-Lymphocytes cytology, B-Lymphocytes metabolism, Cell Count, Cell Lineage, Cells, Cultured, Flow Cytometry, Gene Targeting, Hematopoietic Stem Cells metabolism, Mice, Mice, Mutant Strains, Myeloid Cells pathology, Splenomegaly pathology, T-Lymphocytes cytology, T-Lymphocytes metabolism, Thymus Gland cytology, Hematopoiesis genetics, Leukemia genetics, Mutation genetics, Myelodysplastic Syndromes genetics, Repressor Proteins genetics
- Abstract
The Additional sex combs like 1 (Asxl1) gene is 1 of 3 mammalian homologs of the Additional sex combs (Asx) gene of Drosophila. Asx is unusual because it is required to maintain both activation and silencing of Hox genes in flies and mice. Asxl proteins are characterized by an amino terminal homology domain, by interaction domains for nuclear receptors, and by a C-terminal plant homeodomain protein-protein interaction domain. A recent study of patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) revealed a high incidence of truncation mutations that would delete the PHD domain of ASXL1. Here, we show that Asxl1 is expressed in all hematopoietic cell fractions analyzed. Asxl1 knockout mice exhibit defects in frequency of differentiation of lymphoid and myeloid progenitors, but not in multipotent progenitors. We do not detect effects on hematopoietic stem cells, or in peripheral blood. Notably, we do not detect severe myelodysplastic phenotypes or leukemia in this loss-of-function model. We conclude that Asxl1 is needed for normal hematopoiesis. The mild phenotypes observed may be because other Asxl genes have redundant function with Asxl1, or alternatively, MDS or oncogenic phenotypes may result from gain-of-function Asxl mutations caused by genomic amplification, gene fusion, or truncation of Asxl1.
- Published
- 2010
- Full Text
- View/download PDF
24. Speech errors reflect the phonotactic constraints in recently spoken syllables, but not in recently heard syllables.
- Author
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Warker JA, Xu Y, Dell GS, and Fisher C
- Subjects
- Adult, Auditory Perception physiology, Female, Humans, Male, Memory physiology, Psychomotor Performance physiology, Recognition, Psychology physiology, Reproducibility of Results, Verbal Learning, Young Adult, Speech physiology, Speech Perception physiology
- Abstract
Adults rapidly learn phonotactic constraints from brief production or perception experience. Three experiments asked whether this learning is modality-specific, occurring separately in production and perception, or whether perception transfers to production. Participant pairs took turns repeating syllables in which particular consonants were restricted to particular syllable positions. Speakers' errors reflected learning of the constraints present in the sequences they produced, regardless of whether their partner produced syllables with the same constraints, or opposing constraints. Although partial transfer could be induced (Experiment 3), simply hearing and encoding syllables produced by others did not affect speech production to the extent that error patterns were altered. Learning of new phonotactic constraints was predominantly restricted to the modality in which those constraints were experienced.
- Published
- 2009
- Full Text
- View/download PDF
25. Can an agent's false belief be corrected by an appropriate communication? Psychological reasoning in 18-month-old infants.
- Author
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Song HJ, Onishi KH, Baillargeon R, and Fisher C
- Subjects
- Female, Humans, Infant, Male, Space Perception physiology, Child Development physiology, Cognition physiology, Communication, Mental Processes physiology
- Abstract
Do 18-month-olds understand that an agent's false belief can be corrected by an appropriate, though not an inappropriate, communication? In Experiment 1, infants watched a series of events involving two agents, a ball, and two containers: a box and a cup. To start, agent1 played with the ball and then hid it in the box, while agent2 looked on. Next, in agent1's absence, agent2 moved the ball from the box to the cup. When agent1 returned, agent2 told her "The ball is in the cup!" (informative-intervention condition) or "I like the cup!" (uninformative-intervention condition). During test, agent1 reached for either the box (box event) or the cup (cup event). In the informative-intervention condition, infants who saw the box event looked reliably longer than those who saw the cup event; in the uninformative-intervention condition, the reverse pattern was found. These results suggest that infants expected agent1's false belief about the ball's location to be corrected when she was told "The ball is in the cup!", but not "I like the cup!". In Experiment 2, agent2 simply pointed to the ball's new location, and infants again expected agent1's false belief to be corrected. These and control results provide additional evidence that infants in the second year of life can attribute false beliefs to agents. In addition, the results suggest that by 18 months of age infants expect agents' false beliefs to be corrected by relevant communications involving words or gestures.
- Published
- 2008
- Full Text
- View/download PDF
26. What does syntax say about space? 2-year-olds use sentence structure to learn new prepositions.
- Author
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Fisher C, Klingler SL, and Song HJ
- Subjects
- Child, Preschool, Female, Humans, Linguistics, Male, Language, Space Perception, Speech, Verbal Learning
- Abstract
Children as young as two use sentence structure to learn the meanings of verbs. We probed the generality of sensitivity to sentence structure by moving to a different semantic and syntactic domain, spatial prepositions. Twenty-six-month-olds used sentence structure to determine whether a new word was an object-category name (This is a corp!) or a spatial-relational term (This is acorp my box!). We argue that children rely on the intimate relationship between nouns in sentences and semantic arguments of predicate terms: Noting that a new word takes noun arguments identifies the new word as a predicate term, and directs the child's attention to relations among its arguments.
- Published
- 2006
- Full Text
- View/download PDF
27. Can infants attribute to an agent a disposition to perform a particular action?
- Author
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Song HJ, Baillargeon R, and Fisher C
- Subjects
- Analysis of Variance, Female, Humans, Infant, Male, Statistics, Nonparametric, Child Development, Cognition, Goals, Social Perception
- Abstract
The present research investigated whether 13.5-month-old infants would attribute to an actor a disposition to perform a recurring action, and would then use this information to predict which of two new objects-one that could be used to perform the action and one that could not-the actor would grasp next. During familiarization, the infants watched an actor slide various objects forward and backward on an apparatus floor. During test, the infants saw two new identical objects placed side by side: one stood inside a short frame that left little room for sliding; the other stood inside a longer frame that left ample room for sliding. The infants who saw the actor grasp the object inside the short frame looked reliably longer than those who saw the actor grasp the object inside the long frame. This and control results from a lifting condition provide evidence that by 13.5 months, infants can attribute to an actor a disposition to perform a particular action.
- Published
- 2005
- Full Text
- View/download PDF
28. Infants learn phonotactic regularities from brief auditory experience.
- Author
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Chambers KE, Onishi KH, and Fisher C
- Subjects
- Acoustic Stimulation, Female, Humans, Infant, Male, Random Allocation, Child Language, Phonetics, Speech Perception, Verbal Learning
- Abstract
Two experiments investigated whether novel phonotactic regularities, not present in English, could be acquired by 16.5-month-old infants from brief auditory experience. Subjects listened to consonant-vowel-consonant syllables in which particular consonants were artificially restricted to either initial or final position (e.g. /baep/ not /paeb/). In a later head-turn preference test, infants listened longer to new syllables that violated the experimental phonotactic constraints than to new syllables that honored them. Thus, infants rapidly learned phonotactic regularities from brief auditory experience and extended them to unstudied syllables, documenting the sensitivity of the infant's language processing system to abstractions over linguistic experience.
- Published
- 2003
- Full Text
- View/download PDF
29. Learning phonotactic constraints from brief auditory experience.
- Author
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Onishi KH, Chambers KE, and Fisher C
- Subjects
- Adult, Female, Humans, Male, Psycholinguistics, Mental Recall, Phonetics, Speech Perception, Verbal Learning
- Abstract
Three experiments asked whether phonotactic regularities not present in English could be acquired by adult English speakers from brief listening experience. Subjects listened to consonant-vowel-consonant (CVC) syllables displaying restrictions on consonant position. Responses in a later speeded repetition task revealed rapid learning of (a) first-order regularities in which consonants were restricted to particular positions (e.g. [baep] not *[paeb]), and (b) second-order regularities in which consonant position depended on the adjacent vowel (e.g. [baep] or [pIb], not *[paeb] or *[bIp]). No evidence of learning was found for second-order regularities in which consonant position depended on speaker's voice. These results demonstrated that phonotactic constraints are rapidly learned from listening experience and that some types of contingencies (consonant-vowel) are more easily learned than others (consonant-voice).
- Published
- 2002
- Full Text
- View/download PDF
30. The role of abstract syntactic knowledge in language acquisition: a reply to Tomasello (2000).
- Author
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Fisher C
- Subjects
- Child, Preschool, Concept Formation, Female, Humans, Infant, Male, Psycholinguistics, Verbal Behavior, Language Development, Semantics
- Abstract
In his paper "Do young children have adult syntactic competence?" Tomasello (Cognition 74 (2000) 209) interprets young children's conservatism in language production as evidence that early language use, and verb use in particular, are based entirely on concrete lexical representations, showing no evidence of abstract syntactic categories such as "verb" or "transitive sentence". In this reply, I argue that Tomasello's interpretation depends on three questionable premises: (a) that anyone with a robust grammatical category of verbs would use new verbs in unattested sentence constructions; (b) that there are no reasons other than lack of syntactic competence for lexical effects in language use; and (c) that children always interpret a new verb presented in the context of an action on an object as a causal action verb, and therefore as one they should use transitively. I review evidence against all of these assumptions. Tomasello's data, among others', show that children indeed learn item-specific facts about verbs and other lexical items - as they must, to become competent speakers of their native language. However, other data suggest that more abstract descriptions of linguistic input also play a role in early language use. To achieve a complete picture of how children learn their native languages, we must explore the interactions of lexical and more abstract syntactic knowledge in language acquisition.
- Published
- 2002
- Full Text
- View/download PDF
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