bluuebunny/crossref_metadata_2025 huggingface dataset:
High-resolution three-dimensional spin- and angle-resolved photoelectron spectrometer using vacuum ultraviolet laser light
Authors: Yaji Koichiro , Harasawa Ayumi , Kuroda Kenta , Toyohisa Sogen , Nakayama Mitsuhiro , Ishida Yukiaki , Fukushima Akiko , Watanabe Shuntaro , Chen Chuangtian , Komori Fumio , Shin Shik
Published: May 2016

We describe a spin- and angle-resolved photoelectron spectroscopy (SARPES) apparatus with a vacuum-ultraviolet (VUV) laser (hν = 6.994 eV) developed at the Laser and Synchrotron Research Center at the Institute for Solid State Physics, The University of Tokyo. The spectrometer consists of a hemispherical photoelectron analyzer equipped with an electron deflector function and twin very-low-energy-electron-diffraction-type spin detectors, which allows us to analyze the spin vector of a photoelectron three-dimensionally with both high energy and angular resolutions. The combination of the high-performance spectrometer and the high-photon-flux VUV laser can achieve an energy resolution of 1.7 meV for SARPES. We demonstrate that the present laser-SARPES machine realizes a quick SARPES on the spin-split band structure of a Bi(111) film even with 7 meV energy and 0.7∘ angular resolutions along the entrance-slit direction. This laser-SARPES machine is applicable to the investigation of spin-dependent electronic states on an energy scale of a few meV.
A highly miniaturized vacuum package for a trapped ion atomic clock
Authors: Schwindt Peter D. D. , Jau Yuan-Yu , Partner Heather , Casias Adrian , Wagner Adrian R. , Moorman Matthew , Manginell Ronald P. , Kellogg James R. , Prestage John D.
Published: May 2016

We report on the development of a highly miniaturized vacuum package for use in an atomic clock utilizing trapped ytterbium-171 ions. The vacuum package is approximately 1 cm3 in size and contains a linear quadrupole RF Paul ion trap, miniature neutral Yb sources, and a non-evaporable getter pump. We describe the fabrication process for making the Yb sources and assembling the vacuum package. To prepare the vacuum package for ion trapping, it was evacuated, baked at a high temperature, and then back filled with a helium buffer gas. Once appropriate vacuum conditions were achieved in the package, it was sealed with a copper pinch-off and was subsequently pumped only by the non-evaporable getter. We demonstrated ion trapping in this vacuum package and the operation of an atomic clock, stabilizing a local oscillator to the 12.6 GHz hyperfine transition of 171Y b+. The fractional frequency stability of the clock was measured to be 2 × 10−11/τ1/2.
Wave function continuity and the diagonal Born-Oppenheimer correction at conical intersections
Authors: Meek Garrett A. , Levine Benjamin G.
Published: May 2016

We demonstrate that though exact in principle, the expansion of the total molecular wave function as a sum over adiabatic Born-Oppenheimer (BO) vibronic states makes inclusion of the second-derivative nonadiabatic energy term near conical intersections practically problematic. In order to construct a well-behaved molecular wave function that has density at a conical intersection, the individual BO vibronic states in the summation must be discontinuous. When the second-derivative nonadiabatic terms are added to the Hamiltonian, singularities in the diagonal BO corrections (DBOCs) of the individual BO states arise from these discontinuities. In contrast to the well-known singularities in the first-derivative couplings at conical intersections, these singularities are non-integrable, resulting in undefined DBOC matrix elements. Though these singularities suggest that the exact molecular wave function may not have density at the conical intersection point, there is no physical basis for this constraint. Instead, the singularities are artifacts of the chosen basis of discontinuous functions. We also demonstrate that continuity of the total molecular wave function does not require continuity of the individual adiabatic nuclear wave functions. We classify nonadiabatic molecular dynamics methods according to the constraints placed on wave function continuity and analyze their formal properties. Based on our analysis, it is recommended that the DBOC be neglected when employing mixed quantum-classical methods and certain approximate quantum dynamical methods in the adiabatic representation.
Cation ratio and ferroelectric properties of TbMnO3 epitaxial films grown by pulsed laser deposition
Authors: Shimamoto K. , Döbeli M. , Lippert T. , Schneider C. W.
Published: May 2016

The cation ratio, crystal structure, and ferroelectric properties of TbMnO3 films on (010) oriented YAlO3 substrates grown by pulsed laser deposition were investigated. We found that the cation ratio is altered by the background gas pressure, and that stoichiometric films have larger critical thicknesses than Tb-rich films. The ferroelectric order was severely disturbed in Tb-rich films showing a lower transition temperature and a smaller polarization. In addition, frequency dispersion was observed in the dielectric response of relaxed stoichiometric TbMnO3 films, which may be introduced by defects due to strain relaxation.
Nonlinear interaction of kinetic Alfvén waves and ion acoustic waves in coronal loops
Authors: Sharma Prachi , Yadav Nitin , Sharma R. P.
Published: May 2016

Over the years, coronal heating has been the most fascinating question among the scientific community. In the present article, a heating mechanism has been proposed based on the wave–wave interaction. Under this wave–wave interaction, the high frequency kinetic Alfvén wave interacts with the low frequency ion acoustic wave. These waves are three dimensionally propagating and nonlinearly coupled through ponderomotive nonlinearity. A numerical code based on pseudo-spectral technique has been developed for solving these normalized dynamical equations. Localization of kinetic Alfvén wave field has been examined, and magnetic power spectrum has also been analyzed which shows the cascading of energy to higher wavenumbers, and this cascading has been found to have Kolmogorov scaling, i.e., k−5/3. A breakpoint appears after Kolmogorov scaling and next to this spectral break; a steeper scaling has been obtained. The presented nonlinear interaction for coronal loops plasmas is suggested to generate turbulent spectrum having Kolmogorov scaling in the inertial range and steepened scaling in the dissipation range. Since Kolmogorov turbulence is considered as the main source for coronal heating; therefore, the suggested mechanism will be a useful tool to understand the mystery of coronal loop heating through Kolmogorov turbulence and dissipation.
E × B flow velocity deduced from the poloidal motion of fluctuation patterns in neutral beam injected L-mode plasmas on KSTAR
Authors: Lee W. , Leem J. , Yun G. S. , Park H. K. , Ko S. H. , Choi M. J. , Wang W. X. , Budny R. V. , Ethier S. , Park Y. S. , Luhmann N. C. , Domier C. W. , Lee K. D. , Ko W. H. , Kim K. W. ,   KSTAR Team
Published: May 2016

A method for direct assessment of the equilibrium E × B flow velocity (E×B flow shear is responsible for the turbulence suppression and transport reduction in tokamak plasmas) is investigated based on two facts. The first one is that the apparent poloidal rotation speed of density fluctuation patterns is close to the turbulence rotation speed in the direction perpendicular to the local magnetic field line within the flux surface. And the second “well-known” fact is that the turbulence rotation velocity consists of the equilibrium E × B flow velocity and intrinsic phase velocity of turbulence in the E × B flow frame. In the core region of the low confinement (L-mode) discharges where a strong toroidal rotation is induced by neutral beam injection, the apparent poloidal velocities (and turbulence rotation velocities) are good approximations of the E×B flow velocities since linear gyrokinetic simulations suggest that the intrinsic phase velocity of the dominant turbulence is significantly lower than the apparent poloidal velocity. In the neutral beam injected L-mode plasmas, temporal and spatial scales of the measured turbulence are studied by comparing with the local equilibrium parameters relevant to the ion-scale turbulence.
Effects of substrate orientation on the growth of InSb nanostructures by molecular beam epitaxy
Authors: Chou C. Y. , Torfi A. , Pei C. , Wang W. I.
Published: May 2016

In this work, the effects of substrate orientation on InSb quantum structure growth by molecular beam epitaxy (MBE) are presented. Motivated by the observation that (411) evolves naturally as a stable facet during MBE crystal growth, comparison studies have been carried out to investigate the effects of the crystal orientation of the underlying GaSb substrate on the growth of InSb by MBE. By depositing InSb on a number of different substrate orientations, namely: (100), (311), (411), and (511), a higher nanostructure density was observed on the (411) surface compared with the other orientations. This result suggests that the (411) orientation presents a superior surface in MBE growth to develop a super-flat GaSb buffer surface, naturally favorable for nanostructure growth.
Linear theory of frequency pulling in gyrotrons
Authors: Nusinovich Gregory S. , Luo Li , Liu Pu-Kun
Published: May 2016

The effect of the electron beam on the gyrotron operating frequency (the frequency pulling) is studied analytically in the framework of the linear (or small-signal) theory. The theory is applicable for gyrotrons operating at any cyclotron harmonics and in modes with arbitrary axial structures. The present consideration is limited to cases of operation at the fundamental cyclotron resonance and the second harmonic; also two specific axial profiles of the resonator modes are analyzed: the constant and the sinusoidal distributions. In the case of the sinusoidal distribution, we considered the operation in modes with one, two, and three axial variations. It is shown how to use the theory developed for analyzing the frequency tunability due to the frequency pulling effect in a gyrotron with specified parameters of the electron beam.
Loss of RPGR glutamylation underlies the pathogenic mechanism of retinal dystrophy caused by
TTLL5
mutations
Authors: Sun Xun , Park James H. , Gumerson Jessica , Wu Zhijian , Swaroop Anand , Qian Haohua , Roll-Mecak Antonina , Li Tiansen
Published: May 2016

Significance

Mutations affecting two unrelated genes,
retinitis pigmentosa GTPase regulator
(
RPGR
) and
tubulin tyrosine ligase like 5
(
TTLL5
), lead to photoreceptor degeneration and blindness in humans. We find that RPGR function in photoreceptor cilia requires glutamylation by TTLL5. Glutamylation is a poorly understood posttranslational modification that consists of the addition of glutamates to target proteins. Moreover, we find that mice lacking RPGR or TTLL5 exhibit similar phenotypes characterized by photoreceptor degeneration and opsin mislocalization. Our work identifies a novel essential regulator of RPGR and demonstrates that disease-causing mutations in these two genes share a common pathogenic pathway in humans.
Design of a small molecule against an oncogenic noncoding RNA
Authors: Velagapudi Sai Pradeep , Cameron Michael D. , Haga Christopher L. , Rosenberg Laura H. , Lafitte Marie , Duckett Derek R. , Phinney Donald G. , Disney Matthew D.
Published: May 2016

Significance

The goal of precision medicine is to identify selective drugs that modulate disease-causing biomolecules. This slow process often involves developing a high-throughput screen to test millions of potential drugs to find a few that affect the biomolecule. Here, we describe a facile approach using a disease-causing biomolecule’s sequence to enable design of specific drugs, eliminating arduous and time-consuming screens. By using the sequence of a non–protein-coding, oncogenic RNA, we designed a drug specifically targeting the RNA’s folded structure. In cells and animals, the drug inhibits its target, killing cancer cells while leaving healthy cells unaffected. Thus, a preclinical anticancer drug candidate can be quickly designed from sequence.
Restricting nonclassical MHC genes coevolve with TRAV genes used by innate-like T cells in mammals
Authors: Boudinot Pierre , Mondot Stanislas , Jouneau Luc , Teyton Luc , Lefranc Marie-Paule , Lantz Olivier
Published: May 2016

Significance

The conservation and cross-reactivity between species of the T-cell receptor (TR)-V regions and restricting major histocompatibility (MH) molecules characterizing innate-like T cells, natural killer T (NKT) and mucosal-associated invariant T (MAIT), indicate important functions for these cells. Yet, we show that the two MAIT-specific genes, TRAV1 andMR1, have been lost at least three times during the evolution of mammals. In the rabbit, which has few NKT cells and no MR1, we found a candidate invariant TR-α (iTRA) chain and another mammalian MH1Like molecule that seem to coevolve in mammals. Thus, at least three iTRA/MH-like systems were selected during mammalian evolution. The new MH1Like molecule may present a distinct set of antigens to a new innate-like T-cell subset. This study emphasizes the coevolution of TR and MH molecules.
Finite element simulation and experimental investigation of thermal tensioning during welding of DP600 steel
Authors: Pazooki A. M. A. , Hermans M. J. M. , Richardson I. M.
Published: May 2016

The locally introduced heating and cooling cycle of welding generates residual stresses and distortion. Costly post-weld heat treatments are required in order to reduce welding residual stresses and distortion. Thermal tensioning is one of the more promising in-process techniques to control welding distortion and can be classified into transient thermal tensioning (TTT) and side heating (SH). In thermal tensioning additional heat sources are applied during welding. If the additional heaters are close to the weld centre line and influence the thermal field of the weld, the process is called TTT. If there is no interference to the thermal field of the weld, the process is called SH. In this work, the SH during welding of 2 mm thick DP600 steels has been extensively investigated using numerical and experimental approaches. The thermal and mechanical fields during conventional welding and SH were examined by means of finite element models, and validated by comparison with experimental observation of temperature, distortion and residual stresses. The microstructure was investigated experimentally.
Novel Glaucomys volans vocalizations in Indiana and evidence of geographic variation in high frequency communication
Authors: Eisinger Joseph W. , Scheibe John S. , Flaherty Elizabeth A.
Published: May 2016

The study of ultrasonic signaling has provided important insights into the ecology of bats and marine mammals, but it is poorly understood in other mammalian taxa. Recently, ultrasonic and high frequency vocalizations were described in southern flying squirrels (Glaucomys volans) in the southeastern United States and Ontario, Canada. Notable differences in many call characteristics suggest regional variation in G. volans communication. We evaluated this observation of regional variation by examining G. volans communication in a little studied portion of their range, the Central Hardwoods Region of the United States. We recorded calls of wild G. volans near West Point, Indiana, with Anabat II ultrasonic recorders. We described frequency and time characteristics of recorded calls, categorized call syllables into types, and used a canonical discriminant function analysis to refine our classification. Our analyses yielded 11 distinct types of G. volans syllables, 7 of which are unlike any calls described in other portions of the species range. This suggests G. volans either communicates in distinct regional dialects or has a much larger call repertoire than previously known. We recommend the creation of locally specific call libraries across the range of G. volans to ensure accuracy in the study of high frequency communication.
A stellar feedback origin for neutral hydrogen in high-redshift quasar-mass haloes
Authors: Faucher-Giguère Claude-André , Feldmann Robert , Quataert Eliot , Kereš Dušan , Hopkins Philip F. , Murray Norman
Published: May 2016

Observations reveal that quasar host haloes at z ∼ 2 have large covering fractions of cool dense gas (≳60 per cent for Lyman limit systems within a projected virial radius). Most simulations have so far failed to explain these large observed covering fractions. We analyse a new set of 15 simulated massive haloes with explicit stellar feedback from the FIRE project, covering the halo mass range Mh ≈ 2 × 1012 − 1013 M⊙ at z = 2. This extends our previous analysis of the circum-galactic medium of high-redshift galaxies to more massive haloes. Active galactic nuclei (AGN) feedback is not included in these simulations. We find Lyman limit system covering fractions consistent with those observed around quasars. The large H i covering fractions arise from star formation-driven galactic winds, including winds from low-mass satellite galaxies that interact with cosmological filaments. We show that it is necessary to resolve these satellite galaxies and their winds to reproduce the large Lyman limit system covering fractions observed in quasar-mass haloes. Our simulations predict that galaxies occupying dark matter haloes of mass similar to quasars but without a luminous AGN should have Lyman limit system covering fractions comparable to quasars.
Killer immunoglobulin receptor genes in spondyloarthritis
Authors: Kuijpers Taco W. , Vendelbosch Sanne , Berg Merlijn van den , Baeten Dominique L.P.
Published: May 2016

Purpose of review

We focus on the role of killer immunoglobulin receptor (KIR) interactions with the human leukocyte antigens (HLA)-B27 ligand and the potential contribution of KIR-expressing natural killer and T cells in spondyloarthritis, more specifically in ankylosing spondylitis (AS).

Recent findings

In AS strong epidemiological evidence of significant genetic associations with the major histocompatibility complex was convincingly identified. HLA-B27-positive first-degree relatives of AS cases are 5–16 times more likely to develop disease than HLA-B27-positive carriers in the general community. The GWAS era has enabled rapid progress in identifying non-major histocompatibility complex associations of AS.

These findings show a number of important pathways in AS pathogenesis, including the IL-23–IL-17 pathway, aminopeptidases, peptide presentation, and KIR–HLA-B27 interactions. Studies using genetic markers, including KIRs may be used for a risk assessment about whom may benefit most from the various treatment protocols in spondyloarthritis, now that alternative therapeutic options have become feasible.
Stress Ulcer Prophylaxis
Authors: Barletta Jeffrey F. , Bruno Jeffrey J. , Buckley Mitchell S. , Cook Deborah J.
Published: May 2016

Objectives:

Stress ulcer prophylaxis is commonly administered to critically ill patients for the prevention of clinically important stress-related mucosal bleeding from the upper gastrointestinal tract. Despite widespread incorporation of stress ulcer prophylaxis into practice around the world, questions are emerging about its indications and impact. This clinically focused article will review current controversies related to stress ulcer prophylaxis for critically ill adult patients, including bleeding frequency, risk factors, comparative efficacy, adverse effect profile, and overall cost-effectiveness of the available stress ulcer prophylaxis regimens.

Data Sources:

A MEDLINE search was conducted from inception through August 2015.

Study Selection:

Selected publications describing stress ulcer prophylaxis in adult patients were retrieved (original research, systematic reviews, and practice guidelines); their bibliographies were also reviewed to identify additional pertinent publications.

Data Extraction:

Data from relevant publications were abstracted and summarized.

Data Synthesis:

The existing evidence is organized to describe the patients most likely to benefit from stress ulcer prophylaxis, review the comparative efficacy of proton pump inhibitors and histamine 2 receptor antagonists, the adverse effects of stress ulcer prophylaxis, and overall cost-effectiveness.

Conclusions:

Many stress ulcer prophylaxis recommendations are based on older studies at risk of bias, which may not be applicable to modern practice. Stress ulcer prophylaxis should be limited to patients considered to be at high risk for clinically important bleeding. When evaluating only the trials at low risk for bias, the evidence does not clearly support lower bleeding rates with proton pump inhibitors over histamine 2 receptor antagonists; however, proton pump inhibitors appear to be the dominant drug class used worldwide today. The current rate of upper gastrointestinal bleeding and the relative adverse effects of acid suppression on infectious risk may drive not only the effectiveness, but also the cost-effectiveness of stress ulcer prophylaxis today. Research is currently underway to better address these issues.
Severe Psoriasis Flare After Anti-Programmed Death Ligand 1 (PD-L1) Therapy for Metastatic Non–Small Cell Lung Cancer (NSCLC)
Authors: Chia Puey Ling , John Thomas
Published: May 2016

Immunomodulatory agents that target PD-1 and its ligand (PD-L1) are being increasingly used in the management of lung cancer. Potential immune-related adverse events include dermatological complications which mostly are of low grade severity. The use of immune checkpoint inhibitors may lead to the exacerbation of autoimmune conditions. We report a case of a documented psoriasis flare with anti-PD-1 treatment for lung cancer.
Prospective Controlled Study of Buttock Fat Transfer Using Ultrasound and Photographic Measurements
Authors: Swanson Eric
Published: May 2016

Background:

Buttock fat transfer is now the preferred method for gluteal augmentation. However, its efficacy has not been well-documented using measurements.

Methods:

Twenty-five consecutive patients underwent buttock fat transfer performed by the author. Twenty-one patients returned for measurements ≥3 months after surgery (inclusion rate, 84%). A separate group of 25 patients undergoing cosmetic surgery without buttock fat transfer served as controls. All patients underwent superwet liposuction using total intravenous anesthesia and no prone positioning. A closed filtration system was used to collect the fat. Subcutaneous fat thickness was assessed using ultrasound imaging. Measurements were made on standardized photographs. The data were controlled for change in body mass index. Clinical data were also evaluated.

Results:

The mean fat volume injected per buttock was 287 mL (range, 70–550 mL). Ultrasound measurements detected a significant increase in the subcutaneous fat thickness (P ≤ 0.001), with mean increments of 0.66 cm for the right buttock and 0.86 cm for the left buttock and no significant change for control patients. The mean calculated fat retention, based on the measured surface area injected, was 66%. Photographic measurements of buttock projection revealed a significant increase in treated patients (P < 0.01) and no significant change in control patients. There were no clinical complications at either recipient or donor sites and no evidence of oily cysts on ultrasound examinations.

Conclusions:

Photographic and ultrasound measurements, and clinical findings, confirm that buttock fat transfer effectively and safely increases buttock projection.
Thrombospondin-4 divergently regulates voltage-gated Ca2+ channel subtypes in sensory neurons after nerve injury
Authors: Pan Bin , Guo Yuan , Wu Hsiang-En , Park John , Trinh Van Nancy , Luo Z. David , Hogan Quinn H.
Published: May 2016

Loss of high-voltage–activated (HVA) calcium current (ICa) and gain of low-voltage–activated (LVA) ICa after painful peripheral nerve injury cause elevated excitability in sensory neurons. Nerve injury is also accompanied by increased expression of the extracellular matrix glycoprotein thrombospondin-4 (TSP4), and interruption of TSP4 function can reverse or prevent behavioral hypersensitivity after injury. We therefore investigated TSP4 regulation of ICa in dorsal root ganglion (DRG) neurons. During depolarization adequate to activate HVA ICa, TSP4 decreases both N- and L-type ICa and the associated intracellular calcium transient. In contrast, TSP4 increases ICa and the intracellular calcium signal after low-voltage depolarization, which we confirmed is due to ICa through T-type channels. These effects are blocked by gabapentin, which ameliorates neuropathic pain by targeting the α2δ1 calcium subunit. Injury-induced changes of HVA and LVA ICa are attenuated in TSP4 knockout mice. In the neuropathic pain model of spinal nerve ligation, TSP4 application did not further regulate ICa of injured DRG neurons. Taken together, these findings suggest that elevated TSP4 after peripheral nerve injury may contribute to hypersensitivity of peripheral sensory systems by decreasing HVA and increasing LVA in DRG neurons by targeting the α2δ1 calcium subunit. Controlling TSP4 overexpression in peripheral sensory neurons may be a target for analgesic drug development for neuropathic pain.
Increasing Therapist Productivity: Using Lean Principles in the Rehabilitation Department of an Academic Medical Center
Authors: Johnson Diana , Snedeker Kristie , Swoboda Michael , Zalieckas Cheryl , Dorsey Rachel , Nohe Cassandra , Smith Paige , Roche Renuka
Published: May 2016

The Department of Rehabilitation Services, within the University of Maryland Medical Center's 650-bed academic medical center, was experiencing difficulty in meeting productivity standards. Therapists in the outpatient division believed they were not spending enough time performing billable patient care activities. Therapists in the inpatient division had difficulty keeping pace with the volume of incoming referrals. Collectively, these issues caused dissatisfaction among referral sources and frustration among the staff within the rehabilitation department. The department undertook a phased approach to address these issues that included examining the evidence, using Lean process improvement principles, and employing transformational leadership strategies to drive improvements in productivity and efficiency. The lessons learned support the importance of having meaningful metrics appropriate for the patient population served, the use of Lean as an effective tool for improving productivity in rehabilitation departments, the impact of engaging staff at the grassroots level, and the importance of having commitment from leaders. The study findings have implications for not only rehabilitation and hospital leadership, but CEOs and managers of any business who need to eliminate waste or increase staff productivity.
Chaos in the Clinic: Characteristics and Consequences of Practices Perceived as Chaotic
Authors: Perez Hector R. , Beyrouty Matthew , Bennett Katelyn , Baier Manwell Linda , Brown Roger L. , Linzer Mark , Schwartz Mark D.
Published: May 2016

The Minimizing Error, Maximizing Outcome (MEMO) study of clinics in New York City, Chicago, and Wisconsin linked primary care work experiences to physician stress. We analyzed MEMO data to determine how chaos in the clinic was associated with work conditions and quality of care measures. Surveys and medical record audits determined practice characteristics and medical errors, respectively. Physicians rated clinic atmosphere on a scale of 1 (calm) to 5 (chaotic). Chaotic clinics were defined as practices rated either 4 or 5 by greater than 50% of clinic physicians. Forty of 112 MEMO clinics (36%) were chaotic. Compared with nonchaotic practices, these clinics served more minority and Medicaid patients and had a greater likelihood of clinic bottlenecks such as phone access (both p < .01). Physicians in chaotic clinics reported lower work control and job satisfaction, less emphasis on teamwork and professionalism, more stress and burnout, and a higher likelihood of leaving the practice within 2 years (all p < .05). Chaotic clinics had higher rates of medical errors and more missed opportunities to provide preventative services (both p < .05). More research should examine the effectiveness of organizational interventions to decrease chaos in the clinic and to mitigate its effects on patient safety.
Interprofessional Implementation of a Pain/Sedation Guideline on a Trauma Intensive Care Unit
Authors: Sacco Tara L. , LaRiccia Brenton
Published: May 2016

Trauma patients experience pain and agitation during their hospitalization. Many complications have been noted both in the absence of symptom management and the in presence of oversedation/narcotization. To combat noted untoward effects of pain and sedation management, an interprofessional team convened to develop a pain and sedation guideline for use in a trauma intensive care unit. Guideline development began with a comprehensive review of the literature. With the input of unit stakeholders, a nurse-driven analgosedation guideline was implemented for a 6-month trial. During this time, unit champions were integral to successful trial execution. Outcome measurement included patient and unit outcomes, nursing satisfaction, and a pre- and postimplementation patient comparison. Following implementation, unit length of stay decreased by 4.16% and there was a 17.81% decrease in average time on the ventilator following the initiation of weaning. Patient reports of nurse sensitivity and responsiveness to pain increased from 93.7 to 94.9. Nurses reported satisfaction with the practice change and improvements in care. In comparing pre- and postimplementation patient data, there was a significant decrease in mean analgesic treatment duration and an increase in the use of antipsychotics for delirium management. Following the trial period, this guideline was permanently adopted across the adult critical care service. The development of a nurse-driven analgosedation guideline was noted to be both feasible and successful.
Outcomes After Concomitant Procedures with Left Ventricular Assist Device Implantation: Implications by Device Type and Indication
Authors: Maltais Simon , Haglund Nicholas A. , Davis Mary E. , Aaronson Keith D. , Pagani Francis D. , Dunlay Shannon M. , Stulak John M.
Published: May 2016

Guidelines for performing concomitant procedures (CPs) in patients undergoing continuous flow-left ventricular assist device (CF-LVAD) implantation are unclear. The impact of an increased surgical complexity outside the constraint of landmark clinical trials has not been reported. From May 2004 to December 2013, 614 patients (499 males, 81%) underwent CF-LVAD implant at our institutions. Median age was 57 ± 13 years and 364 (59%) were bridge to transplantation (BTT). Survival and device-related complications were analyzed and stratified based on the surgical intervention. A total of 398 patients (65%) underwent CF-LVAD implantation without CPs. The remaining patients (35%, n = 216) were grouped according to various CPs. Survival was comparable between groups and not influenced by the CP, device type, or indication for implant. Time-to-first device-related adverse event was shorter in patients with CPs. Regression analysis revealed only increased age (p = 0.03), increase in baseline creatinine (p = 0.002), cardiopulmonary bypass time (p = 0.03), and decreased body mass index (p = 0.03) were predictors of mortality, whereas only age (p = 0.006) and prior sternotomy (p = 0.02) were related to adverse device-related events. Performing CPs leads to comparable survival and device-related outcomes after implant. The decision to perform CPs should be balanced with age, preoperative renal dysfunction, and projected complexity of surgery.
Comparative Assessment of 4 Methods to Analyze MGMT Status in a Series of 121 Glioblastoma Patients
Authors: Hsu Chih-Yi , Ho Hsiang-Ling , Lin Shih-Chieh , Chen Ming-Hsiung , Hsu Sanford P-C. , Yen Yu-Shu , Guo Wan-Yuo , Ho Donald Ming-Tak
Published: May 2016

The O6-methylguanine-DNA-methyltranferase (MGMT) status is a powerful predictor of response to temozolomide for newly diagnosed glioblastoma (GBM) patients, and it is commonly assessed by immunohistochemistry (IHC), methylation-specific polymerase chain reaction (MSP), quantitative real-time MSP (qMSP), and/or pyrosequencing (PSQ). This study was to compare their predictive power of prognosis in 121 newly diagnosed GBM patients using multivariate Cox regression with bootstrapping. MGMT status tested by IHC, MSP, qMSP, or PSQ all showed significant correlation with the progression-free survival and overall survival of GBM patients. The predictive power of IHC for progression-free survival and overall survival was lower than those of the methylation assays, but their differences were not significant. Performing additional methylation assay, especially PSQ, could better predict the prognosis of patients with IHC− tumors. MGMT status tested by IHC, MSP, qMSP, or PSQ all showed prognostic significance. An additional MGMT methylation assay, of which PSQ appeared to be the best, could improve the predictive power for GBM patients with MGMT IHC− tumors.
Comprehensive Immunohistochemical Study of Programmed Cell Death Ligand 1 (PD-L1)
Authors: Inaguma Shingo , Wang Zengfeng , Lasota Jerzy , Sarlomo-Rikala Maarit , McCue Peter A. , Ikeda Hiroshi , Miettinen Markku
Published: May 2016

Programmed cell death 1/programmed cell death ligand (PD-1/PD-Ls) axis is crucial for the modulation of immune responses and self-tolerance. Also, aberrant PD-L1 expression on the tumor cells or tumor-associated inflammatory cells accelerates immune evasion of tumor cells. In the past decade, PD-1/PD-L immune checkpoint inhibitors were introduced to cancer treatment trials and, in some cases, showed significant anticancer effects. PD-L1 immunohistochemical staining is considered a potential predictor of clinical response to PD-1/PD-L immune checkpoint inhibitor treatment. However, immunohistochemical data on PD-L1 expression in different types of cancer especially rare entities remain incomplete. In this study, PD-L1 expression was immunohistochemically analyzed in 5536 tumors including germ cell, epithelial, mesenchymal, melanocytic/neuroectodermal, and lymphohematopoietic tumors, as well as in a set of human normal tissues including a fetus. Immunohistochemical analysis was performed with E1L3N rabbit monoclonal antibody and Leica Bond Max automation using multitumor blocks containing up to 70 tumor samples. PD-L1 was constitutively and strongly expressed in placental trophoblasts as well as choriocarcinomas and trophoblastic components of germ cell tumors. Also, the neoplastic cells of classical Hodgkin lymphoma, anaplastic large cell lymphoma, schwannoma, thymoma, and squamous cell carcinoma of various sites frequently expressed PD-L1. In gastrointestinal adenocarcinomas, PD-L1-expression was associated with EBER positivity and mismatch-repair deficiency. In addition, PD-L1 was variably expressed in non-neoplastic macrophages and dendritic cells. PD-L1 immunohistochemistry may have some role in the immunophenotypic differential diagnosis of tumors and pinpointing potential candidates for anti-PD-1/PD-L immune checkpoint therapy.
Two Cases of Carcinosarcomas of the Ovary Involved in Hereditary Cancer Syndromes
Authors: Carnevali Ileana W. , Cimetti Laura , Sahnane Nora , Libera Laura , Cavallero Alessandra , Formenti Giorgio , Riva Cristina , Tibiletti Maria Grazia
Published: May 2016

Ovarian carcinosarcomas (OCS), also known as malignant mixed mesodermal/Müllerian tumors, are rare neoplasms (1%–4% of all malignant ovarian tumors) composed of high-grade malignant epithelial and mesenchymal elements. OCS occurs in older women. It is associated with a poor outcome and is usually not involved in inherited cancer syndromes. We present 2 cases of OCS; one arising in a patient with a pathogenetic BRCA1 mutation and the other in a woman affected by Lynch Syndrome (LS) carrying a MSH6 germline mutation. To the best of our knowledge, this is the first time that this second type of case has been reported. In this study, we investigated somatic impairment of the wild-type BRCA1 and MSH6 alleles in the OCS of these 2 patients. We also explored in both OCS, the occurrence of TP53 loss of function, which is a genetic alteration known to occur in BRCA-linked ovarian tumorigenesis but not in LS tumors. Moreover, we also provide further data about the histogenesis of OCS.
Review of Lung and Pleural Biopsies Received in a Gynecologic Pathology Department Over a 14-Yr Period
Authors: Vella Josefa E. O. , Ganesan Raji , Hirschowitz Lynn
Published: May 2016

Review of pulmonary biopsies received by Birmingham Women’s Hospital to identify which gynecologic tumors most commonly metastasize to lung or pleura, and which may first present with pulmonary metastases. We reviewed all pulmonary biopsies over a 14-yr period. There were 25 lung and 9 pleural biopsies, from 33 patients. Twenty-one patients had known gynecologic tumors (1 vulval, 1 cervical, 9 endometrial, 4 uterine mesenchymal, and 6 ovarian). Eighteen of the 21 biopsies had been referred from other hospitals; in 4 cases review lead to an altered diagnosis. Three of the 21 biopsies had been sent directly to Birmingham Women’s Hospital. The interval between primary diagnosis and pulmonary metastasis was known in 18/21 cases and ranged from 1 to 17 yr. Nine of 21 (43%) had metastatic endometrial carcinoma; the International Federation of Gynecology and Obstetrics (FIGO) stage was known in 7/8 cases: Stage I in 5, and II and IIIA in the remaining 2 cases. Of the further 12 patients with no history of gynecologic malignancy, 4 had pleural metastases from ovarian carcinoma, 3 had primary lung carcinoma, 3 had carcinoma of unknown primary, 1 had endometrial stromal sarcoma, and 1 with a suspected Müllerian tumor was lost to follow-up. Pulmonary metastasis can occur many years after a diagnosis of gynecologic neoplasia—usually endometrial carcinoma, even after initial presentation at low stage. It may also be the initial manifestation in some cases—particularly ovarian carcinoma with pleural involvement. Specialist review of lung and pleural biopsies is important to confirm the diagnosis and optimize patient management.
D-Dimer Levels and Traditional Risk Factors Are Associated With Incident Hypertension Among HIV-Infected Individuals Initiating Antiretroviral Therapy in Uganda
Authors: Okello Samson , Asiimwe Stephen B. , Kanyesigye Michael , Muyindike Winnie R. , Boum Yap , Mwebesa Bosco B. , Haberer Jessica E. , Huang Yong , Williams Kenneth , Burdo Tricia H. , Tracy Russell P. , Bangsberg David R. , Mocello A. Rain , Martin Jeffrey N. , Hunt Peter W. , Siedner Mark J.
Published: May 2016

Objectives:

We sought to describe blood pressure (BP) changes after antiretroviral therapy (ART) initiation and evaluate the association of markers of inflammation with incident hypertension in a cohort of HIV-infected individuals in Uganda.

Methods:

We used mixed effects linear regression to model changes in systolic BP over time among a cohort of HIV-infected individuals initiating ART in Uganda. After exclusion of participants with preexisting hypertension, we identified participants with normal BP throughout follow-up (controls) and those with elevated BP on ≥3 consecutive visits (cases). Before ART initiation, participants had testing for interleukin 6, kynurenine/tryptophan ratio, lipopolysaccharide, soluble CD14, soluble CD163, and D-dimer and those with viral suppression at 6 months during ART had repeat tests. We fit logistic regression models to estimate associations between biomarkers and risk of incident hypertension.

Results:

In the entire cohort, systolic BP increased by 9.6 mm Hg/yr (95% CI: 7.3 to 11.8) in the first 6 months of ART, then plateaued. Traditional factors: male gender (adjusted odds ratio (AOR) 2.76, 95% CI: 1.34 to 5.68), age (AOR 1.09, 95% CI: 1.04 to 1.13), overweight (AOR 4.48, 95% CI: 1.83 to 10.97), and a CD4 count <100 cells (AOR 3.08, 95% CI: 1.07 to 8.89) were associated with incident hypertension. After adjusting for these, D-dimer levels at month 6 were inversely associated with incident hypertension (AOR 0.61, 95% CI: 0.37 to 0.99). Although not significant, similar associations were seen with sCD14 and kynurenine/tryptophan ratio.

Conclusion:

BP increases early after ART initiation in Ugandans. Traditional risk factors, rather than immune activation, were associated with incident hypertension in this population.
Improved Detection of Recurrent Hepatocellular Carcinomas in Arterial Phase With CAIPIRINHA-Dixon-TWIST-Volumetric Interpolated Breath-Hold Examination
Authors: Qu Jinrong , Han Shuai , Zhang Hongkai , Liu Hui , Wang Zhaoqi , Kamel Ihab R. , Berthold Kiefer , Dominik Nickel Marcel , Zhang Shouning , Dong Yafeng , Jiang Lina , Liu Cuicui , Li Hailiang
Published: May 2016

Purpose

The aim of this study was to assess the detection rate of recurrent hepatocellular carcinoma (HCC) in arterial phase using multiarterial CAIPIRINHA-Dixon-TWIST-VIBE (MA-CDT-VIBE).

Materials and Methods

Fifty-eight patients with possible recurrence of HCC were retrospectively included in this cohort. Patients were scanned with a prototype dynamic contrast-enhanced breath-hold CDT-VIBE sequence, which included 6 arterial subphases with a temporal resolution of 2.64 seconds on a 3 T scanner. Absence and presence of recurrence was documented by consensus of 2 experienced radiologists using magnetic resonance imaging multiphase imaging and follow-up evaluation. The third of 6 arterial subphases was considered the equivalent-to-conventional single arterial phase from the contrast bolus timing perspective. The detection rate of recurrent HCCs in arterial phase by another 2 independent experienced readers was compared for all 6 arterial subphases of MA-CDT-VIBE and the equivalent-to-conventional single arterial phase. Interreader agreement was also calculated.

Results

Of the 55 patients reviewed, 46 patients (201 lesions) had recurrent HCC and 9 patients had no recurrence. There was an excellent interreader agreement for both MA-CDT-VIBE (κ = 1.000, P < 0.0001) and the equivalent-to-conventional single arterial phase (κ = 0.850, P < 0.0001). MA-CDT-VIBE showed the detection rate of 100% for all lesions with the diameter of less than 1 cm, 1 to 2 cm, and more than 2 cm. The equivalent-to-conventional single arterial phase resulted in the detection rate of 81.1% and 83.1% for all recurrent HCCs by the 2 readers, respectively, with 78.7% and 83.6% for lesions measuring less than 1 cm, 79.2% and 81.2% for lesions measuring 1 to 2 cm, and 89.7% and 87.2% for lesions measuring more than 2 cm.

Conclusions

Compared with the equivalent-to-conventional single arterial phase, MA-CDT-VIBE with 6 arterial subphases demonstrated higher detection rate of recurrent HCCs in arterial phase and provided a wider arterial observation window, especially for recurrent HCCs less than 2 cm in diameter.
Facilitated Diagnosis of Pneumothoraces in Newborn Mice Using X-ray Dark-Field Radiography
Authors: Hellbach Katharina , Yaroshenko Andre , Willer Konstantin , Pritzke Tina , Baumann Alena , Hesse Nina , Auweter Sigrid , Reiser Maximilian F. , Eickelberg Oliver , Pfeiffer Franz , Hilgendorff Anne , Meinel Felix G.
Published: May 2016

Objective

The aim of this study was to evaluate the diagnostic value of x-ray dark-field imaging in projection radiography-based depiction of pneumothoraces in the neonatal murine lung, a potentially life-threatening medical condition that requires a timely and correct diagnosis.

Materials and Methods

By the use of a unique preclinical model, 7-day-old C57Bl/6N mice received mechanical ventilation for 2 or 8 hours with oxygen-rich gas (Fio
2 = 0.4; n = 24). Unventilated mice either spontaneously breathed oxygen-rich gas (Fio
2 = 0.4) for 2 or 8 hours or room air (n = 22). At the end of the experiment, lungs were inflated with a standardized volume of air after a lethal dose of pentobarbital was administered to the pups. All lungs were imaged with a prototype grating-based small-animal scanner to acquire x-ray transmission and dark-field radiographs. Image contrast between the air-filled pleural space and lung tissue was quantified for both transmission and dark-field radiograms. After the independent expert's assessment, 2 blinded readers evaluated all dark-field and transmission images for the presence or absence of pneumothoraces. Contrast ratios, diagnostic accuracy, as well as reader's confidence and interreader agreement were recorded for both imaging modalities.

Results

Evaluation of both x-ray transmission and dark-field radiographs by independent experts revealed the development of a total of 10 pneumothoraces in 8 mice. Here, the contrast ratio between the air-filled pleural space of the pneumothoraces and the lung tissue was significantly higher in the dark field (8.4 ± 3.5) when compared with the transmission images (5.1 ± 2.8; P < 0.05). Accordingly, the readers' diagnostic confidence for the diagnosis of pneumothoraces was significantly higher for dark-field compared with transmission images (P = 0.001). Interreader agreement improved from moderate for the analysis of transmission images alone (κ = 0.41) to very good when analyzing dark-field images alone (κ = 0.90) or in combination with transmission images (κ = 0.88). Diagnostic accuracy significantly improved for the analysis of dark-field images alone (P = 0.04) or in combination with transmission images (P = 0.02), compared with the analysis of transmission radiographs only.

Conclusions

The significant improvement in contrast ratios between lung parenchyma and free air in the dark-field images allows the facilitated detection of pneumothoraces in the newborn mouse. These preclinical experiments indicate the potential of the technique for future clinical applications.
MRI monitoring of spinal cord changes in patients with multiple sclerosis
Authors: Rovira Alex , de Stefano Nicola
Published: May 2016

Purpose of review

We analyze recent data on technical aspects, clinical indications, and imaging features of spinal cord MRI in multiple sclerosis, and on the value of this examination for assessing the type and extension of spinal cord damage, and for predicting prognosis in patients with this disease.

Recent findings

Spinal cord MRI on patients with multiple sclerosis is technically challenging and a standardized protocol that optimizes the accuracy of this examination is essential, particularly as recent studies have shown its value for diagnostic and prognostic purposes. Several recent studies have proven the potential value of new, quantitative spinal cord magnetic resonance metrics for assessing the type and degree of spinal cord damage. Although these measures can bring new insights into the understanding of the disease, there is not enough evidence to support their use outside the research scenario.

Neurologists and neuroradiologists should be aware of the added value of conventional spinal cord MRI in the initial diagnosis and monitoring of multiple sclerosis. The use of advanced quantitative magnetic resonance techniques, which better assess the degree of irreversible tissue damage within the spinal cord, is mainly restricted to clinical research and cannot yet be incorporated into the daily clinical practice.