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Search Results: 1 - 10 of 168280 matches for " Carolyn E. Behrendt "
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Donor killer immunoglobulin-like receptor genes and reactivation of cytomegalovirus after HLA-matched hematopoietic stem-cell transplantation: HLA-C allotype is an essential cofactor
Carolyn E. Behrendt,John A. Zaia
Frontiers in Immunology , 2013, DOI: 10.3389/fimmu.2013.00036
Abstract: Natural killer (NK) cells whose killer immunoglobulin-like receptors (KIRs) recognize human leukocyte antigen (HLA) ligand are “licensed” for activity. In contrast, non-licensed NK cells display KIRs for which ligand is absent from the self genotype and are usually hyporesponsive. Surprisingly, non-licensed cells are active in tumor control after hematopoietic stem-cell transplantation (HSCT) and dominate NK response to murine cytomegalovirus (CMV) infection. From those reports, we hypothesized that control of human CMV early after HSCT is influenced by donor KIR genes whose HLA ligand is absent-from-genotype of HLA-matched donor and recipient. To investigate, we studied CMV reactivation through Day 100 after grafts involving CMV-seropositive donor and/or recipient. A multivariate proportional rates model controlled for variability in surveillance and established covariates including acute graft-versus-host disease; statistical significance was adjusted for testing of multiple KIRs with identified HLA class I ligand (2DL1, 2DL2/3, 2DS1, 2DS2, full-length 2DS4, 3DL1/3DS1, 3DL2). Among HSCT recipients (n = 286), CMV reactivation-free survival time varied with individual donor KIR genes evolutionarily specific for HLA-C: when ligand was absent from the donor/recipient genotype, inhibitory KIRs 2DL2 (P < 0.0001) and 2DL1 (P = 0.015) each predicted inferior outcome, and activating KIRs 2DS2 (P < 0.0001), 2DS1 (P = 0.016), and 2DS4 (P = 0.016) each predicted superior outcome. Otherwise, with ligand present-in-genotype, donor KIR genes had no effect. In conclusion, early after HLA-matched HSCT, individual inhibitory and activating KIR genes have qualitatively different effects on risk of CMV reactivation; unexpectedly, absence of HLA-C ligand from the donor/recipient genotype constitutes an essential cofactor in these associations. Being KIR- and HLA-C-specific, these findings are independent of licensing via alternate NK cell receptors (NKG2A, NKG2C) that recognize HLA-E.
Preoperative Concern about Nausea and Vomiting and Postoperative Use of Antiemetics among Patients Undergoing Breast Cancer-Related Surgery  [PDF]
John L. Raytis, Carolyn E. Behrendt, Richard Obenchain, Matthew Loscalzo, Michael W. Lew
Open Journal of Anesthesiology (OJAnes) , 2018, DOI: 10.4236/ojanes.2018.86020
Abstract: Background: Postoperative nausea and vomiting (PONV) can lead to complications and increased healthcare costs. We investigated whether patient preoperative concern about PONV is associated with postoperative antiemetic use, independently of Apfel score. Methods: Patients eligible for study were English- or Spanish-speaking women with breast cancer undergoing mastectomy, lumpectomy or reconstructive surgery as outpatients during July 2014-July 2017, when the pre-anesthesia clinic routinely screened for preoperative concern via tablet computer-based survey. Excluded were patients who did not rate their concern or lacked Apfel score. Risk factors for concern were evaluated in a multinomial model adjusted for multiple hypotheses. Using generalized linear regression, preoperative concern was tested for association with number of antiemetics administered in the postanesthesia care unit. Results:?Of preoperative surveys, 7.1% (58/812) were excluded for missing data, leaving n = 754 surveys contributed by n = 706 subjects (age 26 - 80 years). Patient preoperative concern ranged from none (32.8%), mild (30.2%), moderate (22.9%), severe (7.8%), to very severe (6.2%). Adjusted for age, concern was increased by history of motion sickness (Odds Ratio 1.51, 95% Confidence Interval 1.11 - 2.06) and history of PONV (9.02, 6.30 - 12.90) and decreased by prior surgery without PONV (0.35, 0.23 - 0.53) and Spanish as primary language (0.42, 0.25 - 0.68). Number of postoperative antiemetics, usually 1 (41.2%) or 2 (33.4%) drugs, was unassociated with preoperative concern before or after adjustment for Apfel score. Conclusions: Among women undergoing breast cancer-related surgery, preoperative concern about PONV varies by prior history of PONV and motion sickness and by ethnicity. However, preoperative concern is not associated with postoperative antiemetic medications.
Sea ice draft in the Weddell Sea, measured by upward looking sonars
A. Behrendt,W. Dierking,E. Fahrbach,H. Witte
Earth System Science Data Discussions , 2012, DOI: 10.5194/essdd-5-805-2012
Abstract: The presented database contains time-referenced sea ice draft values from upward looking sonar (ULS) measurements in the Weddell Sea, Antarctica. The sea ice draft data can be used to infer the thickness of the ice. They were collected during the period 1990–2008. In total, the database includes measurements from 13 locations in the Weddell Sea and was generated from more than 3.7 million measurements of sea ice draft. The files contain uncorrected raw drafts, corrected drafts from two different methods and the basic parameters measured by the ULS. The measurement principle, the data processing procedure and the quality control are described in detail. To account for the unknown speed of sound in the water column above the ULS, two correction methods were applied to the data. The first method is based on defining a reference level from the identification of open water leads. The second method uses a model of sound speed in the oceanic mixed layer and is applied to ice draft in austral winter. Both methods are discussed and their accuracy is estimated. Finally, selected results of the processing are presented. The data can be downloaded under http://doi.pangaea.de/10.1594/PANGAEA.785565.
On Legacy
Larissa Behrendt
Public Space : the Journal of Law and Social Justice , 2009,
Abstract: (Courtesy of abc.net.au) When John Howard's minister for Indigenous Affairs, Mal Brough, authorised the Northern Territory intervention, public response was mixed. Was it a necessarily extreme response to meet an extreme situation, or an inherently racist piece of legislation that didn't engage with the key problems? More than 2 years and a new government later, controversy still surrounds the intervention, even as it has been modified by the new minister Jenny Macklin. Delivering the final Sydney PEN lectures for 2009, aboriginal lawyer, academic and activist Larissa Behrendt delivered a damning assessment of the last two years, and the ideological agenda that she believes underlies the intervention.
Impact of obstructive sleep apnea on the occurrence of restenosis after elective percutaneous coronary intervention in ischemic heart disease
Stephan Steiner, Per O Schueller, Marcus G Hennersdorf, Dominik Behrendt, Bodo E Strauer
Respiratory Research , 2008, DOI: 10.1186/1465-9921-9-50
Abstract: To determine whether sleep apnea is associated with increased late lumen loss and restenosis after percutaneous coronary intervention.78 patients with coronary artery disease who underwent elective percutaneous coronary intervention were divided in 2 groups: 43 patients with an apnea hypopnea – Index < 10/h (group I) and 35 pt. with obstructive sleep apnea and an AHI > 10/h (group II). Late lumen loss, a marker of restenosis, was determined using quantitative coronary angiography after 6.9 ± 3.1 months.Angiographic restenosis (>50% luminal diameter), was present in 6 (14%) of group I and in 9 (25%) of group II (p = 0.11). Late lumen loss was significant higher in pt. with an AHI > 10/h (0.7 ± 0.69 mm vs. 0.38 ± 0.37 mm, p = 0.01). Among these 35 patients, 21(60%) used their CPAP devices regularly. There was a marginally lower late lumen loss in treated patients, nevertheless, this difference did not reach statistical significance (0.57 ± 0.47 mm vs. 0.99 ± 0.86 mm, p = 0.08). There was no difference in late lumen loss between treated patients and the group I (p = 0.206).In summary, patients with OSA and coronary artery disease have a higher degree of late lumen loss, which is a marker of restenosis and vessel remodeling after elective percutaneous intervention.Obstructive sleep apnea (OSA) is a common disorder defined by upper airway obstruction, apnea and nocturnal hypoxia. There is a prevalence of OSA in patients with coronary artery disease of up to 50% [1-3]. Beyond this high prevalence, the occurrence of OSA is associated with an advanced state of atherosclerosis [4] and a worse prognosis in these patients [5-7]. In the last decade, there is growing evidence that OSA acts as a cardiovascular risk factor, independent of associated traditional risk factors (e.g. arterial hypertension, dyslipedemia, obesitas).Percutaneous transluminal coronary angioplasty (PTCA) has proved effective in reducing myocardial ischemia and clinical symptoms in patients with coronary ar
A Role for the Immediate Early Gene Product c-fos in Imprinting T Cells with Short-Term Memory for Signal Summation
Carolyn E. Clark,Milena Hasan,Philippe Bousso
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018916
Abstract: T cells often make sequential contacts with multiple DCs in the lymph nodes and are likely to be equipped with mechanisms that allow them to sum up the successive signals received. We found that a period of stimulation as short as two hours could imprint on a T cell a “biochemical memory” of that activation signal that persisted for several hours. This was evidenced by more rapid induction of activation markers and earlier commitment to proliferation upon subsequent stimulation, even when that secondary stimulation occurred hours later. Upregulation of the immediate early gene product c-fos, a component of the AP-1 transcription factor, was maximal by 1–2 hours of stimulation, and protein levels remained elevated for several hours after stimulus withdrawal. Moreover, phosphorylated forms of c-fos that are stable and transcriptionally active persisted for a least a day. Upon brief antigenic stimulation in vivo, we also observed a rapid upregulation of c-fos that could be boosted by subsequent stimulation. Accumulation of phosphorylated c-fos may therefore serve as a biochemical fingerprint of previous suboptimal stimulation, leaving the T cell poised to rapidly resume its activation program upon its next encounter with an antigen-bearing DC.
A Single Polar Residue and Distinct Membrane Topologies Impact the Function of the Infectious Bronchitis Coronavirus E Protein
Travis R. Ruch,Carolyn E. Machamer
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002674
Abstract: The coronavirus E protein is a small membrane protein with a single predicted hydrophobic domain (HD), and has a poorly defined role in infection. The E protein is thought to promote virion assembly, which occurs in the Golgi region of infected cells. It has also been implicated in the release of infectious particles after budding. The E protein has ion channel activity in vitro, although a role for channel activity in infection has not been established. Furthermore, the membrane topology of the E protein is of considerable debate, and the protein may adopt more than one topology during infection. We previously showed that the HD of the infectious bronchitis virus (IBV) E protein is required for the efficient release of infectious virus, an activity that correlated with disruption of the secretory pathway. Here we report that a single residue within the hydrophobic domain, Thr16, is required for secretory pathway disruption. Substitutions of other residues for Thr16 were not tolerated. Mutations of Thr16 did not impact virus assembly as judged by virus-like particle production, suggesting that alteration of secretory pathway and assembly are independent activities. We also examined how the membrane topology of IBV E affected its function by generating mutant versions that adopted either a transmembrane or membrane hairpin topology. We found that a transmembrane topology was required for disrupting the secretory pathway, but was less efficient for virus-like particle production. The hairpin version of E was unable to disrupt the secretory pathway or produce particles. The findings reported here identify properties of the E protein that are important for its function, and provide insight into how the E protein may perform multiple roles during infection.
The Coronavirus E Protein: Assembly and Beyond
Travis R. Ruch,Carolyn E. Machamer
Viruses , 2012, DOI: 10.3390/v4030363
Abstract: The coronavirus E protein is a small membrane protein that has an important role in the assembly of virions. Recent studies have indicated that the E protein has functions during infection beyond assembly, including in virus egress and in the host stress response. Additionally, the E protein has ion channel activity, interacts with host proteins, and may have multiple membrane topologies. The goal of this review is to highlight the properties and functions of the E protein, and speculate on how they may be related.
Toward a theoretical model of quality-of-life appraisal: Implications of findings from studies of response shift
Bruce D Rapkin, Carolyn E Schwartz
Health and Quality of Life Outcomes , 2004, DOI: 10.1186/1477-7525-2-14
Abstract: Quality of life (QOL) assessment involves a class of measurement fundamental to many aspects of health care planning and outcomes research. It is relevant for assessing symptoms, side effects of treatment, disease progression, satisfaction with care, quality of support services, unmet needs, and appraisal of health and health care options. Patient self-report is the most desirable, and often the only way to obtain this critical information. Thus, accurate and meaningful measures of the various dimensions of QOL are vitally important. Here, we 1) review evidence from the response shift literature regarding different cognitive processes that influence QOL appraisal; 2) build upon the Sprangers and Schwartz [1] model, to develop a theoretically grounded measurement model that addresses the phenomenology of QOL appraisal and suggest methods of assessing this phenomenology; and 3) discuss how appraisal assessment can be incorporated in statistical and clinical judgment models of QOL, to provide a coherent and empirically-testable definition of response shift.The importance of QOL makes it critical to improve and refine measures to understand patients' experiences of health, illness, and treatment. Unfortunately, pervasive paradoxical and counterintuitive findings raise questions about what QOL measures actually assess and how scores should be interpreted: people with severe chronic illnesses report QOL equal or superior to less severely ill or healthy people [2-8], and consistent disparities arise between clinical measures of health and patients' own evaluations [9-11]. Indeed, several studies show that health care providers and significant others tend to underestimate patients' QOL compared with patients' evaluations [12-15]. In short, QOL measures do not consistently distinguish known groups, are often only weakly related to objective criteria, and show little convergence across measurement perspectives.These inconsistent findings support the notion of underlying diffe
Reconsidering the psychometrics of quality of life assessment in light of response shift and appraisal
Carolyn E Schwartz, Bruce D Rapkin
Health and Quality of Life Outcomes , 2004, DOI: 10.1186/1477-7525-2-16
Abstract: Studies examining response shift phenomena suggest that underlying processes of appraisal differ across people and over time and can greatly affect how people answer questions on QOL measures. The current generation of QOL measures were, however, not designed to account for response shift phenomena [1], but are based on the assumptions that people use measurement scales consistently and that QOL scale scores are directly comparable across people and over time. As Bjorner, Ware and Kosinski [2] point out, both classical and modern psychometric theories view individual differences in scale usage as sources of error. In these nomothetic approaches, the psychometric properties of QOL instruments are framed in terms of the estimation of underlying QOL "true" scores or "latent" scores. This concept is essentially identical to the approach taken in the measurement of constructs like personality and abilities.We argue that the idea of the true score and related psychometric concepts have been misapplied in QOL measurement because QOL phenomena cannot be appropriately understood in the classical nomothetic measurement paradigm. Rather, we contend that critical properties of QOL measurement are overlooked or relegated to error variance because they do not fit within prevailing psychometric models. Following our companion piece [3], which introduces a new model for conceptualizing and measuring QOL appraisal, we discuss the implications of response shift and appraisal for the psychometric assessment of QOL measures. In sum, our position is that individual differences in cognitive appraisal processes should not be viewed as sources of error in QOL research. Instead, these processes are intrinsic to all QOL measurement. We propose that psychometric models of QOL must be expanded to take differences in appraisal into account by positing the notion of the "contingent true score". We discuss the implications of this concept for assessing the reliability, validity and responsiveness
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