• Differences in xylogenesis between dominant and suppressed trees

  Liu, Shushan; Li, Xiaoxia; Rossi, Sergio; Wang, Lily; Li, Wei; Liang, Eryuan; Leavitt, Steven W; Univ Arizona, Lab Tree Ring Res (BOTANICAL SOC AMER INC, 2018-01-01)

  PREMISE OF THE STUDY: Most dendroecological studies focus on dominant trees, but little is known about the growing season of trees belonging to different size classes and their sensitivity to biotic factors. The objective of this study was to compare the dynamics of xylem formation between dominant and suppressed trees of Abies fabri of similar age growing in the Gongga Mountains, southeastern Tibetan Plateau, and to identify the association between xylem growth and climate. METHODS: The timing and duration of xylogenesis in histological sections were investigated weekly during the 2013-2015 growing seasons. KEY RESULTS: Our investigation found that timing and duration of xylogenesis varied with canopy position and its associated tree size. Xylogenesis started 6-14 days earlier, and ended 5-11 days later in dominant trees than in suppressed trees, resulting in a significantly longer growing season. Dominant trees also exhibited higher temperature sensitivity of tracheid production rate than suppressed trees. CONCLUSIONS: The observed differences in xylogenesis among trees suggested that competition affects tree growth by reducing the growing period in suppressed trees. Representative climate-growth relationships should involve trees of all size classes when evaluating the effects of the environment on forest dynamics.
• A Model-independent Mass and Moderate Eccentricity for beta Pic b

  Dupuy, Trent J.; Brandt, Timothy D.; Kratter, Kaitlin M.; Bowler, Brendan P.; Univ Arizona, Dept Astron; Univ Arizona, Steward Observ (IOP PUBLISHING LTD, 2019-01-20)

  We use a cross-calibration of Hipparcos and Gaia. second data release astrometry for beta Pic to measure the mass of the giant planet beta Pic. b (13 +/- 3 M-Jup) in a comprehensive joint orbit analysis that includes published relative astrometry and radial velocities. Our mass uncertainty is somewhat higher than previous work because our astrometry from the Hipparcos-Gaia Catalog of Accelerations accounts for the error inflation and systematic terms that are required to bring the two data. sets onto a common astrometric reference frame, and because we fit freely for the host-star mass (1.84 +/- 0.05 M-circle dot). This first model-independent mass for a directly imaged planet is inconsistent with cold-start models given the age of the beta Pic moving group (22 +/- 6 Myr) but consistent with hot and warm-start models, concordant with past work. We find a higher eccentricity (0.24 +/- 0.06) for beta Pic b compared to previous orbital fits. If confirmed by future observations, this eccentricity may help explain inner edge, scale height, and brightness asymmetry of beta Pic's disk. It could also potentially signal that beta Pic b has migrated inward to its current location, acquiring its eccentricity from interaction with the 3:1 outer Lindblad resonance in the disk.
• A High-Resolution Global Map of Soil Hydraulic Properties Produced by a Hierarchical Parameterization of a Physically Based Water Retention Model

  Zhang, Yonggen; Schaap, Marcel G.; Zha, Yuanyuan; Univ Arizona, Dept Soil Water & Environm Sci (AMER GEOPHYSICAL UNION, 2018-12)

  A correct quantification of mass and energy exchange processes among Earth's land surface, groundwater, and atmosphere requires an accurate parameterization of soil hydraulic properties. Pedotransfer functions (PTFs) are useful in this regard because they estimate these otherwise difficult to obtain characteristics using texture and other ubiquitous soil data. Most PTFs estimate parameters of empirical hydraulic functions with modest accuracy. In a continued pursuit of improving global-scale PTF estimates, we evaluated whether improvements can be obtained when estimating parameters of hydraulic functions that make physically based assumptions. To this end, we developed a PTF that estimates the parameters of the Kosugi retention and hydraulic conductivity functions (Kosugi, 1994, , 1996, ), which explicitly assume a lognormal pore size distribution and apply the Young-Laplace equation to derive a corresponding pressure head distribution. Using a previously developed combination of machine learning and bootstrapping, the developed five hierarchical PTFs allow for estimates under practical data-poor to data-rich conditions. Using an independent global data set containing nearly 50,000 samples (118,000 retention points), we demonstrated that the new Kosugi-based PTFs outperformed two van Genuchten-based PTFs calibrated on the same data. The new PTFs were applied to a 1x1km(2) global map of texture and bulk density, thus producing maps of the parameters, field capacity, wilting point, plant available water, and associated uncertainties. Soil hydraulic parameters exhibit a much larger variability in the Northern Hemisphere than in the Southern Hemisphere, which is likely due to the geographical distribution of climate zones that affect weathering and sedimentation processes.
• A Deeply Buried Narrow-line Seyfert 1 Nucleus Uncovered in Scattered Light

  Pan, Xiang; Lu, Honglin; Komossa, S.; Xu, Dawei; Yuan, Weimin; Sun, Luming; Smith, Paul S.; Zhang, Shaohua; Jiang, Peng; Yang, Chenwei; Liu, Wenjuan; Jiang, Ning; Rashed, Y. E.; Eckart, A.; Dierkes, Jens; Zhou, Hongyan; Univ Arizona, Steward Observ (IOP PUBLISHING LTD, 2019-01-10)

  We present spectropolarimetric and spectrophotometric observations of the peculiar active galactic nucleus (AGN) SDSS J120300.19+162443.7 (hereafter J1203+1624) at z = 0.1656. Its optical total flux spectra clearly show broad emission lines (BELs) in H alpha and H beta. After removal of narrow emission lines (NELs), the full width at half maximum (FWHM) of the Lorentzian BEL is FWHMBEL approximate to 1270 km s(-1), fulfilling the conventional definition of a narrow-line Seyfert 1 (NLS1) galaxy. However, its NELs are unprecedentedly strong when compared to type 1 AGNs. This, together with its large MIR excess (g - W-4 = 13.172 mag), implies that the observer and the NEL region might see a different ionization continuum. Our optical spectropolarimetry confirms its type 2 nature by detecting a polarized blue continuum and Balmer BELs (FWHMPolarized BEL approximate to 1183 km s(-1)), with a high polarization degree of > 20% in the blue wing. The mass and Eddington rate of the central black hole are estimated based on both transmitted and scattered AGN radiation, which is M-center dot < 2.9 x 10(7) M-circle dot and L-bol/L-Edd > 1.5. Severe extinction of the AGN emission also enables a clear view of the compact host galaxy. The discovery of J1203 +1624 suggests that NLS1 follows the AGN unification scheme, and studying its analogs could blaze a new trail for exploring the connection between black hole growth and star formation in the host galaxy. The interesting features of J1203+1624, like the peculiar NELs and inflowing scattering clouds within the sublimation radius, are worth detailed follow-ups in the future.
• A Comparative Study of the AHP and TOPSIS Techniques for Dam Site Selection Using GIS: A Case Study of Sistan and Baluchestan Province, Iran

  Jozaghi, Ali; Alizadeh, Babak; Hatami, Mohsen; Flood, Ian; Khorrami, Mohammad; Khodaei, Nastaran; Ghasemi Tousi, Erfan; Univ Arizona, Dept Civil & Architectural Engn & Mech (MDPI, 2018-12)

  The application of multiple criteria decision-making (MCDM) techniques in real-life problems has increased in recent years. The need to build advanced decision models with higher capabilities that can support decision-making in a broad spectrum of applications, promotes the integration of MCDM techniques with applicable systems, including artificial intelligence, and Geographic Information Systems (GIS). The Analytic Hierarchy Process (AHP) and Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) are among the most widely adopted MCDM techniques capable of resolving water resources challenges. A critical problem associated with water resource management is dam site selection. This paper presents a comparative analysis of TOPSIS and AHP in the context of decision-making using GIS for dam site selection. The comparison was made based on geographic and water quality criteria. The geographical criteria are geology, land use, sediment, erosion, slope, groundwater, and discharge. The water quality criteria include Soluble Sodium Percentage, Total Dissolved Solid, Potential of Hydrogen, and Electrical Conductivity of water. A ratio estimation procedure was used to determine the weights of these criteria. Both methods were applied for selection of optimal sites for dams in the Sistan and Baluchestan province, Iran. The results show that the TOPSIS method is better suited to the problem of dam site selection for this study area. Actual locations of dams constructed in the area were used to verify the results of both methods.
• Bendamustine with Total Body Irradiation Limits Murine Graft-versus-Host Disease in Part Through Effects on Myeloid-Derived Suppressor Cells

  Stokes, Jessica; Hoffman, Emely A; Molina, Megan S; Eremija, Jelena; Larmonier, Nicolas; Zeng, Yi; Katsanis, Emmanuel; Univ Arizona, Dept Pediat; Univ Arizona, Dept Immunobiol; Univ Arizona, Dept Med; Univ Arizona, Dept Pathol; Univ Arizona, Canc Ctr (ELSEVIER SCIENCE INC, 2019-03-01)

  Graft-versus-host disease (GVHD) remains a significant challenge in allogeneic hematopoietic cell transplantation (HCT). An underinvestigated strategy to reduce GVHD is the modification of the preparative conditioning regimen. In the present study, we aimed to evaluate GVHD associated with bendamustine (BEN) conditioning in conjunction with total body irradiation (TBI) as an alternative to the standard myeloablative regimen of cyclophosphamide (CY) and TBI. We demonstrate that BEN-TBI conditioning, although facilitating complete donor chimerism, results in significantly less GVHD compared with CY-TBI. In BEN-TBI-conditioned mice, suppressive CD11b+Gr-1high myeloid cells are increased in the blood, bone marrow, spleen, and intestines. When Gr-1high cells are depleted before transplantation, the beneficial effects of BEN-TBI are partially lost. Alternatively, administration of granulocyte colony-stimulating factor, which promotes CD11b+Gr-1+ myeloid cell expansion, is associated with a trend toward increased survival in BEN-TBI-conditioned mice. These findings indicate a potential role of myeloid-derived suppressor cells in the mechanism by which BEN allows engraftment with reduced GVHD. BEN-TBI conditioning may present a safer alternative to CY-TBI conditioning for allogeneic HCT.
• A Census of Galaxy Constituents in a Coma Progenitor Observed at > 3

  Shi, Ke; Lee, Kyoung-Soo; Dey, Arjun; Huang, Yun; Malavasi, Nicola; Hung, Chao-Ling; Inami, Hanae; Ashby, Matthew; Duncan, Kenneth; Xue, Rui; Reddy, Naveen; Hong, Sungryong; Jannuzi, Buell T.; Cooper, Michael C.; Gonzalez, Anthony H.; Röttgering, Huub J. A.; Best, Phillip N.; Tasse, Cyril; Univ Arizona, Steward Observ (IOP PUBLISHING LTD, 2019-01-20)

  We present a detailed census of galaxies in and around PC 217.96+32.3, a spectroscopically confirmed Coma analog at z = 3.78. Diverse galaxy types identified in the field include Ly alpha emitters (LAEs), massive star-forming galaxies, and ultramassive galaxies (greater than or similar to 10(11)M(circle dot)) which may have already halted their star formation. The sky distribution of the star-forming galaxies suggests the presence of a significant overdensity (delta(SFG) approximate to 8 +/- 2), which is spatially offset from the previously confirmed members by 3-4 Mpc to the west. Candidate quiescent and post-starburst galaxies are also found in large excess (a factor of similar to 8-15 higher surface density than the field's), although their redshifts are less certain. We estimate that the total enclosed mass traced by the candidate star-forming galaxies is roughly comparable to that of PC 217.96+32.3 traced by the LAEs. We speculate that the true extent of PC 217.96+32.3 may be larger than previously known, half of which is missed by our LAE selection. Alternatively, the newly discovered overdensity may belong to another Coma progenitor not associated with PC 217.96+32.3. Expectations from theory suggest that both scenarios are equally unlikely (<1%) in the cosmic volume probed in our survey. If confirmed as a single structure, its total mass will be well in excess of Coma's, making it an exceptionally large cosmic structure rarely seen even in large cosmological simulations. Finally, we find that the protocluster galaxies follow the same star formation rate-M-* scaling relation as the field galaxies, suggesting that the environmental effect at z similar to 4 is a subtle one at best for normal star-forming galaxies.
• 3D imaging of gems and minerals by multiphoton microscopy

  Cromey, Benjamin; Knox, Ryan J.; Kieu, Khanh; Univ Arizona, Coll Opt Sci (OPTICAL SOC AMER, 2019-02-01)

  Many optical approaches have been used to examine the composition and structure of gemstones, both recently and throughout history. The nonlinear optical behavior of different gemstones has not been investigated, and the higher order terms to the refractive index represent an unused tool for qualifying and examining a stone. We have used a multiphoton microscope to examine the nonlinear optical properties of 36 different gemstones and demonstrate that it is a useful tool for imaging them three-dimensionally up to the millimeter scale below the sample surface. The polarization dependence of second harmonic generation signals was used to examine the crystal orientations inside the minerals. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
• One-Step Method for Instant Generation of Advanced Allogeneic NK Cells

  Lee, Daniel Y; Lim, Kwang Suk; Valencia, Gabriel M; Jung, Minjin; Bull, David A; Won, Young-Wook; Univ Arizona, Coll Med, Dept Surg, Div Cardiothorac Surg (WILEY, 2018-11-01)

  Conventional combinatorial anticancer therapy has shown promising outcomes; still, a significant interest in developing new methods to reinforce and possibly merge chemotherapy and immunotherapy persists. Here, a new one-step method that immediately modifies immune cells into a targeted form of chemoimmunotherapy through spontaneous and rapid incorporation of hydrophobized antibody-drug conjugates (ADCs) on the surface of immune cells is presented. Therapeutic objectives of this approach include targeted delivery of a potent chemotherapeutic agent to avoid adverse effects, enhancing the mobilization of infused immune cells toward tumor sites, and preserving the intense cytotoxic activities of immune cells against tumor cells. The embedding of hydrophobized ADCs on the immune cell membrane using the strategy in this study provides noninvasive, nontoxic, and homogenous modifications that transiently arm immune cells with highly potent cytotoxic drugs targeted toward cancer cells. The resulting surface-engineered immune cells with ADCs significantly suppress the tumor growth and drive the eradication of target cancer cells through combinatorial anticancer effects. This novel strategy allows convenient and timely preparation of advanced chemoimmunotherapy on a single immune cell to treat various types of cancer.
• Dietary Protein and Carbohydrates Affect Immune Function and Performance in a Specialist Herbivore Insect (Manduca sexta)

  Wilson, J Keaton; Ruiz, L; Davidowitz, G; Univ Arizona, Dept Entomol (UNIV CHICAGO PRESS, 2019-01-01)

  Nutrition structures ecology and evolution across all scales of biological organization. It is well known that nutrition can have direct effects on performance and fitness, but indirect effects on physiological systems that mediate biotic interactions have been studied less frequently. Here, we focus on the interaction between nutrition, performance, and the immune system in a specialist herbivorous insect, Manduca sexta. We used a conceptual framework in nutritional ecology (the geometric framework) to examine how changes in diet quality affect aspects of the immune system used for defense against parasitoids. We raised caterpillars throughout their entire larval development on five different experimental diets that varied in protein and carbohydrate content and measured five aspects of the immune system: encapsulation, phenoloxidase activity, prophenoloxidase activity, total hemolymph protein, and hemocyte density. Overall, different parts of the immune function varied in response to interactions between carbohydrates, protein, and intake, but protein reductions had the largest impacts-mostly detrimental. In addition, our data suggest that diet quality mediates the relationship between performance (growth and survival) and immune function, as well as trade-offs among different components of immune function. Our work is the first to examine the interplay between nutrition, performance, and immune function with the geometric framework in a specialist insect herbivore.
• Initial Single-Site Surgical Experience with SMILE: A Comparison of Results to FDA SMILE, and the Earliest and Latest Generation of LASIK

  Moshirfar, Majid; Murri, Michael S; Shah, Tirth J; Linn, Steven H; Ronquillo, Yasmyne; Birdsong, Orry C; Hoopes, Phillips C; Univ Arizona, Coll Med (SPRINGER INTERNATIONAL PUBLISHING AG, 2018-12-01)

  IntroductionThe primary objective was to show our initial surgical single-site experience with small incision lenticule extraction (SMILE) after the official enrollment in March 2017 following Food and Drug Administration (FDA) approval for simple myopia in late 2016 in the United States and, subsequently, compare our results to the earliest and most advanced generation of excimer platforms for laser-assisted in situ keratomileusis (LASIK) surgery.MethodsThis was a retrospective single-site study of 68 eyes from 35 patients who had SMILE surgery. The patients' preoperative and postoperative uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest sphere, manifest cylinder, intraoperative complications, and preoperative and postoperative visual symptoms were collected. We compared our findings to the results from the FDA SMILE study, and to the three earliest (1999-2000) and three of the most updated (2013-2016) platforms for LASIK.ResultsThe cumulative UDVA was 20/20 and 20/40 or better in 74% and 100% of patients, respectively. The intended target refraction was within0.5 and +/- 1.00 D in 80% and 93% of cases, respectively. The prevalence of dry eyes decreased by nearly half from 1-week to the 6-month postoperative interval. Patients noted improvement in glare (17%), halos (17%), fluctuation (25%), and depth perception (8%) at the 6-month interval compared to preoperative levels.Conclusions<his study's findings are consistent with current SMILE reports. Notably, the results are superior to the earliest generation of LASIK, however inferior to the latest excimer platforms. SMILE does meet the efficacy and safety criteria met by FDA; however, there is a definite need for further improvement to reach the superior refractive outcomes produced by the latest generation of LASIK platforms.
• Recording arbitrary polarization states on photorefractive media

  Sanaka, Kaoru; Suzuki, Ryo; Takeuchi, Masato; Takashima, Yuzuru; Moriki, Ryo; Univ Arizona, Coll Opt Sci (SPIE-INT SOC OPTICAL ENGINEERING, 2018)

  We propose a new recording scheme by which arbitrary polarization states are stored in volumetric and polarization insensitive photorefractive materials. In the scheme, Stokes parameters of an arbitrary polarization state are recorded as grating strength by using the relation between the interference intensity in recording process and the diffraction efficiency in reading process. We show the experimental setup to retrieve linear, circular, and elliptic polarization states using a typical non-polarization dependent photorefractive media, an iron-doped lithium niobate crystal. The polarization state introduces an additional degree of freedom for storing information, and is useful for expanding the capacity in holographic data storage.
• Beam steering by digital micro-mirror device for multi-beam and single-chip lidar

  Rodriguez, Joshua M.; Kang, Eunmo; Hellman, Brandon; Chen, Guanghao; Smith, Braden; Gin, Adley; Espinoza, Alonzo; Takashima, Yuzuru; Univ Arizona, Takashima Grp, Coll Opt Sci (SPIE-INT SOC OPTICAL ENGINEERING, 2018)

  A novel method of beam steering, utilizing a mass-produced Digital Micromirror Device (DMD), enables a reliable single chip Light Detection and Ranging (LIDAR) with a large field of view while having minimum moving components. In the single-chip LIDAR, a short-pulsed laser is fired in a synchronous manner to the micromirrors rotation during the transitional state. Since the pulse duration of the laser pulse is substantially short compared to the transitional time of the mirror rotation, virtually the mirror array is frozen in transition at several discrete points, which forms a programmable and blazed grating. The programmable blazed grating efficiently redirects the pulsed light to a single diffraction order among several while employing time of flight measurement. Previously, with a single 905nm nanosecond laser diode and Si avalanche photo diode, a measurement accuracy and rate of <1 cm and 3.34k points/sec, respectively, was demonstrated over a 1m distance range with 48 degrees full field of view and 10 angular resolution. We have also increased the angular resolution by employing multiple laser diodes and a single DMD chip while maintaining a high measurement rate of 3.34k points/s. In addition, we present a pathway to achieve 0.65 degrees resolution with 60 degrees field of view and 23k points/s measurement rate.
• Physical and geometrical hybrid design of two-layer and depth-chirped holographic image guide for see-through glass type head mounted display

  Nakamura, Toshiteru; Takashima, Yuzuru; Univ Arizona, Coll Opt Sci (SPIE-INT SOC OPTICAL ENGINEERING, 2018)

  We designed the image guide with discretely depth-chirped holographic grating for head mounted display to equalize luminance over the Field of View (FOV) and increase throughput. To reduce the time required to optimize depth-chirped pattern, the mathematical optical efficiency prediction method was devised. The design approach enables, rapid turnaround in design process and precise prediction of optical performance of image guide incorporated depth-chirped grating. Display performance of the depth-chirped image guide identified by the mathematical optimization was verified by the geometrical and physical hybrid optical simulation that the RCWA code is integrated to geometrical ray trace code via DLL to incorporate effects of the diffraction. As a results, the design exhibited 315 cd/m(2)/lm for the FOV (35 degrees (H) x 20 degrees (V)) and eye box size (+/- 8.5 mm (H), +/- 6.5 mm (V)). The value of luminance was increased by 37% than unchirped image guide. Uniformity of luminance was further improved, from 33% to 47%. In conclusion, we made clear the effect of depth-chirped image guide to increasing the performance of the image guide.
• Single detector imaging lidar by digital micromirror device for large field-of-view and mid-range mapping applications

  Hellman, Brandon; Smith, Braden; Gin, Adley; Kim, Young-Sik; Chen, Guanghao; Winkler, Paul; McCann, Phillip; Takashima, Yuzuru; Univ Arizona (SPIE-INT SOC OPTICAL ENGINEERING, 2018)

  An imaging lidar system is presented which combines the high speed of a Digital Micromirror Device (DMD) and the higher range of a 1D collimated scanning output. The system employing 1D line object illumination along with DMD placed at focal plane enables flexible optimization of system metrics, such as field of view, angular resolution, maximum range distance and frame rate.
• Light recycling beam steering on a DMD lidar

  Chen, Guanghao; Hellman, Brandon; Rodriguez, Joshua M.; Smith, Braden; Gin, Adley; Takashima, Yuzuru; Univ Arizona, Coll Opt Sci (SPIE-INT SOC OPTICAL ENGINEERING, 2018)

  Spatial light modulators (SLMs) that operate in a phase modulation mode enable beam steering with higher diffraction efficiency compared to amplitude modulation mode, thus potentially be used for an efficient beam steering with no moving part. Currently, Twisted Nematic phase SLMs are widely adopted for phase modulation. However, their refresh rate is typically in the range below kilohertz. Recently, a new method for binary and spatial phase modulation using Digital Micromirror Device (DMD) was proposed by a research group in Germany. In the method, complemental self-images of DMD, corresponding to on-and off-pixels, are formed by two auxiliary optics while adding a pi phase shift between two images. The optics function as recycling of light in a coherent manner. The method enables over kilohertz refresh rate and higher diffraction efficiency in binary phase modulation mode to conventional amplitude binary modulation. As alternatives to the binary phase modulation, we propose and experimentally evaluated high-speed beam steering by DMD based on light recycling. In our experiment, with binary phase modulation mode, system output efficiency reaches 8%. It can be doubled to 16% with light recycling method. Efficiency is still low compared to the reported value of 27% without light recycling. To further increase beam efficiency, system loss was analysed.
• Holography for automotive applications: from HUD to LIDAR

  Draper, Craig T.; McDonald, Joshua; Blanche, Pierre-Alexandre J.; Bigler, Colton M.; Sarma, Kalluri; Univ Arizona, Coll Opt Sci (SPIE-INT SOC OPTICAL ENGINEERING, 2018)

  Holography can offer unique solutions to the specific problems faced by automotive optical systems. Frequently, when possibilities have been exhausted using refractive and reflective designs, diffraction can come to the rescue by opening a new dimension to explore. Holographic optical elements (HOEs), for example, are thin film optics that can advantageously replace lenses, prisms, or mirrors. Head up display (HUD) and LIDAR for autonomous vehicles are two of the systems where our group have used HOEs to provide original answers to the limitations of classical optic. With HUD, HOEs address the problems of the limited field of view, and small eye box usually found in projection systems. Our approach is to recycle the light multiple times inside a waveguide so the combiner can be as large as the entire windshield. In this system, a hologram is used to inject a small image at one end of a waveguide, and another hologram is used to extract the image several times, providing an expanded eye box. In the case of LIDAR systems, non-mechanical beam scanning based on diffractive spatial light modulator (SLM), are only able to achieve an angular range of few degrees. We used multiplexed volume holograms (VH) to amplify the initial diffraction angle from the SLM to achieve up to 4 pi steradian coverage in a compact form factor.
• 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.

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