• Phenytoin and Rifampin Do Not Decrease Levels in Acute Tacrolimus Toxicity

  Lawson, Benjamin O; Seth, Heemesh; Quan, Dan; Univ Arizona, Dept Emergency Med, Coll Med (SAGE PUBLICATIONS LTD, 2018-03-24)

  Tacrolimus is used in bone marrow transplant patients to prevent graft-versus-host disease. There have been few case reports of tacrolimus toxicity (>30 ng/mL) in solid organ recipients as well as in nontransplant patients. Several case reports suggest phenytoin and rifampin decrease tacrolimus levels in toxicity, but does it actually make a difference? A 60-year-old man with acute myeloblastic leukemia after allogenic stem cell transplant with fever, diarrhea, and abdominal pain was transferred to the intensive care unit for persistent hypotension and acute hypoxic respiratory failure requiring intubation. The following day his tacrolimus level was 8.6 ng/mL and creatinine was 2.2 (baseline = 1.8). The patient inadvertently received 15 mg intravenous tacrolimus instead of his scheduled 0.5 mg intravenous. Four hours later, a random tacrolimus level was 36.4 ng/mL. Tacrolimus was discontinued; phenytoin 200 mg BID was started for 4 doses and rifampin was started for 2 doses at 600 mg. Sixteen hours postinjection, tacrolimus level decreased to 26.4 ng/mL and to 9 ng/mL after 64 hours. Creatinine improved to 1.1 after 30 hours. He was extubated 5 days later without any new neurological findings and his creatinine returned to baseline. Our patient received 30 times his daily dose resulting high tacrolimus levels. Assuming there was sufficient time for distribution, our patient's half-life increased to 34.5 hours compared with the reported half-life of 12 hours. The possibilities for this increase include ineffective or harmful effects of the phenytoin/rifampin combination, change in metabolism kinetics at high levels, or other unidentified patient-specific factors. Further studies should be done to ensure that phenytoin and rifampin are safe to give in tacrolimus toxicity.
• Variability of Burnout and Stress Measures in Pediatric Residents: An Exploratory Single-Center Study From the Pediatric Resident Burnout-Resilience Study Consortium

  Reed, Suzanne; Kemper, Kathi J; Schwartz, Alan; Batra, Maneesh; Staples, Betty B; Serwint, Janet R; McClafferty, Hilary; Schubert, Charles J; Wilson, Paria M; Rakowsky, Alex; Chase, Margaret; Mahan, John D; Univ Arizona (SAGE PUBLICATIONS INC, 2018-10-31)

  Residency is a high-risk period for physician burnout. We aimed to determine the short-term stability of factors associated with burnout, application of these data to previous conceptual models, and the relationship of these factors over 3 months. Physician wellness questionnaire results were analyzed at 2 time points 3 months apart. Associations among variables within and across time points were analyzed. Logistic regression was used to predict burnout and compassionate care. A total of 74% of residents completed surveys. Over 3 months, burnout (P=.005) and empathy (P=.04) worsened. The most significant cross-sectional relationship was between stress and emotional exhaustion (time 1 r=0.61, time 2 r=0.68). Resilience was predictive of increased compassionate care and decreased burnout (P<.05). Mindfulness was predictive of decreased burnout (P<.05). Mitigating stress and fostering mindfulness and resilience longitudinally may be key areas of focus for improved wellness in pediatric residents. Larger studies are needed to better develop targeted wellness interventions.
• Virus and CTL dynamics in the extrafollicular and follicular tissue compartments in SIV-infected macaques.

  Wodarz, Dominik; Skinner, Pamela J; Levy, David N; Connick, Elizabeth; Univ Arizona, Div Infect Dis (PUBLIC LIBRARY SCIENCE, 2018-10-01)

  Data from SIV-infected macaques indicate that virus-specific cytotoxic T lymphocytes (CTL) are mostly present in the extrafollicular (EF) compartment of the lymphoid tissue, with reduced homing to the follicular (F) site. This contributes to the majority of the virus being present in the follicle and represents a barrier to virus control. Using mathematical models, we investigate these dynamics. Two models are analyzed. The first assumes that CTL can only become stimulated and expand in the extrafollicular compartment, with migration accounting for the presence of CTL in the follicle. In the second model, follicular CTL can also undergo antigen-induced expansion. Consistent with experimental data, both models predict increased virus compartmentalization in the presence of stronger CTL responses and lower virus loads, and a more pronounced rise of extrafollicular compared to follicular virus during CD8 cell depletion experiments. The models, however, differ in other aspects. The follicular expansion model results in dynamics that promote the clearance of productive infection in the extrafollicular site, with any productively infected cells found being the result of immigration from the follicle. This is not observed in the model without follicular CTL expansion. The models further predict different consequences of introducing engineered, follicular-homing CTL, which has been proposed as a therapeutic means to improve virus control. Without follicular CTL expansion, this is predicted to result in a reduction of virus load in both compartments. The follicular CTL expansion model, however, makes the counter-intuitive prediction that addition of F-homing CTL not only results in a reduction of follicular virus load, but also in an increase in extrafollicular virus replication. These predictions remain to be experimentally tested, which will be relevant for distinguishing between models and for understanding how therapeutic introduction of F-homing CTL might impact the overall dynamics of the infection.
• Provenance of invaders has scale-dependent impacts in a changing wetland ecosystem

  Amatangelo, Kathryn L.; Stevens, Lee; Wilcox, Douglas A.; Jackson, Stephen T.; Sax, Dov F.; Amatangelo, Kathryn L.; Stevens, Lee; Wilcox, Douglas A.; Jackson, Stephen T.; Sax, Dov F.; Univ Arizona, US Geol Survey, Dept Interior Southwest Climate Adapt Sci Ctr; Univ Arizona, Dept Geosci; Univ Arizona, Sch Nat Resources & Environm (PENSOFT PUBL, 2019-11-19)

  Exotic species are associated with a variety of impacts on biodiversity, but it is unclear whether impacts of exotic specks differ from those of native species with similar growth forms or native species invading disturbed sites. We compared presence and abundance of native and exotic invaders with changes in wetland plant species diversity over a 28-year period by re-surveying 22 ponds to identify factors correlated with observed changes. We also compared communities found within dense patches of native and exotic emergent species with similar habits. Within patches, we found no categorical diversity differences between areas dominated by native or exotic emergent species. At the pond scale, the cover of the exotic grass Phragmites australis best predicted change in diversity and evenness over time, likely owing to its significant increase in coverage over the study period. These changes in diversity and evenness were strongest in younger, less successionally-advanced ponds. Changes associated with cover of P. australis in these ponds were not consistent with expected diversity decreases, but instead with a dampening of diversity gains, such that the least-invaded ponds increased in diversity the most over the study period. There were more mixed effects on evenness, ranging from a reduction in evenness gains to actual losses of evenness in the ponds with highest invader cover. In this wetland complex, the habit, origin and invasiveness of species contribute to diversity responses in a scale- and context-dependent fashion. Future efforts to preserve diversity should focus on preventing the arrival and spread of invaders that have the potential to cover large areas at high densities, regardless of their origin. Future studies should also investigate more thoroughly how changes in diversity associated with species invasions are impacted by other ongoing ecosystem changes.
• Resolving "orphaned" non-specific structures using machine learning and natural language processing methods

  Xu, Dongfang; Chong, Steven S; Rodenhausen, Thomas; Cui, Hong; Univ Arizona (PENSOFT PUBL, 2018-08-10)

  Scholarly publications of biodiversity literature contain a vast amount of information in human readable format. The detailed morphological descriptions in these publications contain rich information that can be extracted to facilitate analysis and computational biology research. However, the idiosyncrasies of morphological descriptions still pose a number of challenges to machines. In this work, we demonstrate the use of two different approaches to resolve meronym (i.e. part-of) relations between anatomical parts and their anchor organs, including a syntactic rule-based approach and a SVM-based (support vector machine) method. Both methods made use of domain ontologies. We compared the two approaches with two other baseline methods and the evaluation results show the syntactic methods (92.1% F1 score) outperformed the SVM methods (80.7% F1 score) and the part-of ontologies were valuable knowledge sources for the task. It is notable that the mistakes made by the two approaches rarely overlapped. Additional tests will be conducted on the development version of the Explorer of Taxon Concepts toolkit before we make the functionality publicly available. Meanwhile, we will further investigate and leverage the complementary nature of the two approaches to further drive down the error rate, as in practical application, even a 1% error rate could lead to hundreds of errors.

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