bluuebunny/crossref_metadata_2025 huggingface dataset:
Cutting Edge: T Follicular Helper Cell Differentiation Is Defective in the Absence of Bcl6 BTB Repressor Domain Function
Authors: Nance J. Philip , Bélanger Simon , Johnston Robert J. , Takemori Toshitada , Crotty Shane
Published: May 2015

T follicular helper (Tfh) cells are essential for germinal centers (GCs) and most long-term humoral immunity. Differentiation of Tfh cells depends on the transcriptional repressor B cell CLL/lymphoma 6 (Bcl6). Bcl6 mediates gene repression via the recruitment of corepressors. Currently, it is unknown how Bcl6 recruits corepressors to regulate gene expression of Tfh cells. In this article, we demonstrate, using a mutant form of Bcl6 with two BTB (bric-a-brac, tramtrack, broad-complex) mutations that abrogate corepressor binding, that the Bcl6 BTB domain is required for proper differentiation of Tfh and GC-Tfh cells in vivo. Importantly, we also observe a significant defect in GC B cell development. These results are consistent in multiple contexts, including a novel lymphocytic choriomeningitis virus nucleoprotein-specific TCR-transgenic mouse model. Taken together, these data suggest that the Bcl6 BTB domain is a key mediator of the differentiation of Tfh cells.
Quantitative Profiling of Immune Repertoires for Minor Lymphocyte Counts Using Unique Molecular Identifiers
Authors: Egorov Evgeny S. , Merzlyak Ekaterina M. , Shelenkov Andrew A. , Britanova Olga V. , Sharonov George V. , Staroverov Dmitriy B. , Bolotin Dmitriy A. , Davydov Alexey N. , Barsova Ekaterina , Lebedev Yuriy B. , Shugay Mikhail , Chudakov Dmitriy M.
Published: May 2015

Emerging high-throughput sequencing methods for the analyses of complex structure of TCR and BCR repertoires give a powerful impulse to adaptive immunity studies. However, there are still essential technical obstacles for performing a truly quantitative analysis. Specifically, it remains challenging to obtain comprehensive information on the clonal composition of small lymphocyte populations, such as Ag-specific, functional, or tissue-resident cell subsets isolated by sorting, microdissection, or fine needle aspirates. In this study, we report a robust approach based on unique molecular identifiers that allows profiling Ag receptors for several hundred to thousand lymphocytes while preserving qualitative and quantitative information on clonal composition of the sample. We also describe several general features regarding the data analysis with unique molecular identifiers that are critical for accurate counting of starting molecules in high-throughput sequencing applications.
Neonatal Exposure to Pneumococcal Phosphorylcholine Modulates the Development of House Dust Mite Allergy during Adult Life
Authors: Patel Preeyam S. , Kearney John F.
Published: May 2015

Currently, ∼20% of the global population suffers from an allergic disorder. Allergies and asthma occur at higher rates in developed and industrialized countries. It is clear that many human atopic diseases are initiated neonatally and herald more severe IgE-mediated disorders, including allergic asthma, which is driven by the priming of Th2 effector T cells. The hygiene hypothesis attempts to link the increased excessively sanitary conditions early in life to a default Th2 response and increasing allergic phenomena. Despite the substantial involvement of IgE Abs in such conditions, little attention has been paid to the effects of early microbial exposure on the B cell repertoire prior to the initiation of these diseases. In this study, we use Ab-binding assays to demonstrate that Streptococcus pneumoniae and house dust mite (HDM) bear similar phosphorylcholine (PC) epitopes. Neonatal C57BL/6 mice immunized with a PC-bearing pneumococcal vaccine expressed increased frequencies of PC-specific B cells in the lungs following sensitizing exposure to HDM as adults. Anti-PC IgM Abs in the lung decreased the interaction of HDM with pulmonary APCs and were affiliated with lowered allergy-associated cell infiltration into the lung, IgE production, development of airway hyperresponsiveness, and Th2 T cell priming. Thus, exposure of neonatal mice to PC-bearing pneumococci significantly reduced the development of HDM-induced allergic disease during adult life. Our findings demonstrate that B cells generated against conserved epitopes expressed by bacteria, encountered early in life, are also protective against the development of allergic disease during adult life.
Evolution of surface velocities and ice discharge of Larsen B outlet glaciers from 1995 to 2013
Authors: Wuite J. , Rott H. , Hetzenecker M. , Floricioiu D. , De Rydt J. , Gudmundsson G. H. , Nagler T. , Kern M.
Published: May 2015

Abstract. We use repeat-pass SAR data to produce detailed maps of surface motion covering the glaciers draining into the former Larsen B Ice Shelf, Antarctic Peninsula, for different epochs between 1995 and 2013. We combine the velocity maps with estimates of ice thickness to analyze fluctuations of ice discharge. The collapse of the central and northern sections of the ice shelf in 2002 led to a near-immediate acceleration of tributary glaciers as well as of the remnant ice shelf in Scar Inlet. Velocities of most of the glaciers discharging directly into the ocean remain to date well above the velocities of the pre-collapse period. The response of individual glaciers differs and velocities show significant temporal fluctuations, implying major variations in ice discharge as well. Due to reduced velocity and ice thickness the ice discharge of Crane Glacier decreased from 5.02 Gt a−1 in 2007 to 1.72 Gt a−1 in 2013, whereas Hektoria and Green glaciers continue to show large temporal fluctuations in response to successive stages of frontal retreat. The velocity on Scar Inlet ice shelf increased 2–3-fold since 1995, with the largest increase in the first years after the break-up of the main section of Larsen B. Flask and Leppard glaciers, the largest tributaries to Scar Inlet ice shelf, accelerated. In 2013 their discharge was 38% and 46% higher than in 1995.
Booming tourism industry and urban economic growth
Authors: Deng Taotao , Ma Mulan
Published: May 2015

This article provides an empirical analysis of the risk of the “resource curse” in tourism-dependent economies. Using China`s tourism data for 48 major tourist cities from 2000 to 2012, the article reexamines the direct and indirect effects of tourism booms on urban economic growth within the framework of the resource curse. At the city level, there is some evidence for the presence of Dutch Disease symptoms as a consequence of high dependency on tourism industry. However, physical investment tends to be an important transmission channel via which tourism exerts a positive indirect effect on economic growth. The evidence becomes stronger for cities, which are more dependent on the tourism industry.
A Prospective, Randomized Comparison of Intramuscular Phloroglucinol Versus Oral Misoprostol for Cervix Pretreatment Before Diagnostic Hysteroscopy
Authors: Xu Dong , Zhang Xi , He Jing
Published: May 2015

The aim of this study was to compare the effectiveness and safety of intramuscular phloroglucinol and oral misoprostol for cervix pretreatment before diagnostic hysteroscopy. Several modalities for cervical priming and pain reduction have been adopted to reduce the complications related to cervical dilatation before hysteroscopy. Among them, the prostaglandin analog misoprostol is the most frequently used agent. Phloroglucinol, a spasmolytic, has also been showed to have an effect in inducing cervical dilatation but is rarely used before hysteroscopy. One hundred twenty outpatients undergoing anesthesia-free diagnostic hysteroscopy were randomly assigned to receive 80 mg intramuscular phloroglucinol and 400 mg oral misoprostol before diagnostic hysteroscopy. The main outcome measures were preoperative cervical width, visual analog scales (VAS) for pain, cervical passage time, and adverse reactions. Intramuscular phloroglucinol resulted in a significantly wider cervical width, lower VAS pain score, shorter cervical passage time, and a lower adverse effects rate compared with oral misoprostol. Intramuscular phloroglucinol is more effective and safer than oral misoprostol in inducing proper cervical priming and may be the optimal choice for cervical pretreatment before diagnostic hysteroscopy.
Van Allen Probes investigation of the large‐scale duskward electric field and its role in ring current formation and plasmasphere erosion in the 1 June 2013 storm
Authors: Thaller S. A. , Wygant J. R. , Dai L. , Breneman A. W. , Kersten K. , Cattell C. A. , Bonnell J. W. , Fennell J. F. , Gkioulidou Matina , Kletzing C. A. , De Pascuale S. , Hospodarsky G. B. , Bounds S. R.
Published: May 2015

Using the Van Allen Probes, we investigate the enhancement in the large‐scale duskward convection electric field during the geomagnetic storm (Dst ~ −120 nT) on 1 June 2013 and its role in ring current ion transport and energization and plasmasphere erosion. During this storm, enhancements of ~1–2 mV/m in the duskward electric field in the corotating frame are observed down to L shells as low as ~2.3. A simple model consisting of a dipole magnetic field and constant, azimuthally westward, electric field is used to calculate the earthward and westward drift of 90° pitch angle ions. This model is applied to determine how far earthward ions can drift while remaining on Earth's nightside, given the strength and duration of the convection electric field. The calculation based on this simple model indicates that the enhanced duskward electric field is of sufficient intensity and duration to transport ions from a range of initial locations and initial energies characteristic of (though not observed by the Van Allen Probes) the earthward edge of the plasma sheet during active times (L ~ 6–10 and ~1–20 keV) to the observed location of the 58–267 keV ion population, chosen as representative of the ring current (L ~ 3.5–5.8). According to the model calculation, this transportation should be concurrent with an energization to the range observed, ~58–267 keV. Clear coincidence between the electric field enhancement and both plasmasphere erosion and ring current ion (58–267 keV) pressure enhancements are presented. We show for the first time nearly simultaneous enhancements in the duskward convection electric field, plasmasphere erosion, and increased pressure of 58–267 keV ring current ions. These 58–267 keV ions have energies that are consistent with what they are expected to pick up by gradient B drifting across the electric field. These observations strongly suggest that we are observing the electric field that energizes the ions and produces the erosion of the plasmasphere.
Real‐time imaging of density ducts between the plasmasphere and ionosphere
Authors: Loi Shyeh Tjing , Murphy Tara , Cairns Iver H. , Menk Frederick W. , Waters Colin L. , Erickson Philip J. , Trott Cathryn M. , Hurley‐Walker Natasha , Morgan John , Lenc Emil , Offringa André R. , Bell Martin E. , Ekers Ronald D. , Gaensler B. M. , Lonsdale Colin J. , Feng Lu , Hancock Paul J. , Kaplan David L. , Bernardi G. , Bowman J. D. , Briggs F. , Cappallo R. J. , Deshpande A. A. , Greenhill L. J. , Hazelton B. J. , Johnston‐Hollitt M. , McWhirter S. R. , Mitchell D. A. , Morales M. F. , Morgan E. , Oberoi D. , Ord S. M. , Prabu T. , Shankar N. Udaya , Srivani K. S. , Subrahmanyan R. , Tingay S. J. , Wayth R. B. , Webster R. L. , Williams A. , Williams C. L.
Published: May 2015

Ionization of the Earth's atmosphere by sunlight forms a complex, multilayered plasma environment within the Earth's magnetosphere, the innermost layers being the ionosphere and plasmasphere. The plasmasphere is believed to be embedded with cylindrical density structures (ducts) aligned along the Earth's magnetic field, but direct evidence for these remains scarce. Here we report the first direct wide‐angle observation of an extensive array of field‐aligned ducts bridging the upper ionosphere and inner plasmasphere, using a novel ground‐based imaging technique. We establish their heights and motions by feature tracking and parallax analysis. The structures are strikingly organized, appearing as regularly spaced, alternating tubes of overdensities and underdensities strongly aligned with the Earth's magnetic field. These findings represent the first direct visual evidence for the existence of such structures.
New observations of displacement steps associated with volcano seismic long‐period events, constrained by step table experiments
Authors: Thun Johannes , Lokmer Ivan , Bean Christopher J.
Published: May 2015

Long‐period (LP) volcano seismic events often precede volcanic eruptions and are viewed with considerable interest in hazard assessment. They are usually thought to be associated with resonating fluid‐filled conduits although alternative models involving material failure have recently been proposed. Through recent field experiments, we uncovered a step‐like displacement component associated with some LP events, outside the spectral range of the typically narrow‐band analysis for this kind of event. Bespoke laboratory experiments with step tables show that steps of the order of a few micrometers can be extracted from seismograms, where long‐period noise is estimated and removed with moving median filters. Using these constraints, we observe step‐like ground deformation in LP recordings near the summits of Turrialba and Etna Volcanoes. This represents a previously unobserved static component in the source time history of LP events, with implications for the underlying source process.
Imbalanced land surface water budgets in a numerical weather prediction system
Authors: Kauffeldt Anna , Halldin Sven , Pappenberger Florian , Wetterhall Fredrik , Xu Chong‐Yu , Cloke Hannah L.
Published: May 2015

There has been a significant increase in the skill and resolution of numerical weather prediction models (NWPs) in recent decades, extending the time scales of useful weather predictions. The land surface models (LSMs) of NWPs are often employed in hydrological applications, which raises the question of how hydrologically representative LSMs really are. In this paper, precipitation (P), evaporation (E), and runoff (R) from the European Centre for Medium‐Range Weather Forecasts global models were evaluated against observational products. The forecasts differ substantially from observed data for key hydrological variables. In addition, imbalanced surface water budgets, mostly caused by data assimilation, were found on both global (P‐E) and basin scales (P‐E‐R), with the latter being more important. Modeled surface fluxes should be used with care in hydrological applications, and further improvement in LSMs in terms of process descriptions, resolution, and estimation of uncertainties is needed to accurately describe the land surface water budgets.
Azimuthal flow bursts in the inner plasma sheet and possible connection with SAPS and plasma sheet earthward flow bursts
Authors: Lyons L. R. , Nishimura Y. , Gallardo‐Lacourt B. , Nicolls M. J. , Chen S. , Hampton D. L. , Bristow W. A. , Ruohoniemi J. M. , Nishitani N. , Donovan E. F. , Angelopoulos V.
Published: May 2015

We have combined radar observations and auroral images obtained during the Poker Flat Incoherent Scatter Radar Ion Neutral Observations in the Thermosphere campaign to show the common occurrence of westward moving, localized auroral brightenings near the auroral equatorward boundary and to show their association with azimuthally moving flow bursts near or within the subauroral polarization stream (SAPS) region. These results indicate that the SAPS region, rather than consisting of relatively stable proton precipitation and westward flows, can have rapidly varying flows, with speeds varying from ~100 m/s to ~1 km/s in just a few minutes. The auroral brightenings are associated with bursts of weak electron precipitation that move westward with the westward flow bursts and extend into the SAPS region. Additionally, our observations show evidence that the azimuthally moving flow bursts often connect to earthward (equatorward in the ionosphere) plasma sheet flow bursts. This indicates that rather than stopping or bouncing, some flow bursts turn azimuthally after reaching the inner plasma sheet and lead to the bursts of strong azimuthal flow. Evidence is also seen for a general guiding of the flow bursts by the large‐scale convection pattern, flow bursts within the duskside convection being azimuthally turned to the west, and those within the dawn cell being turned toward the east. The possibility that the SAPS region flow structures considered here may be connected to localized flow enhancements from the polar cap that cross the nightside auroral poleward boundary and lead to flow bursts within the plasma sheet warrants further consideration.
The effect of different solar wind parameters upon significant relativistic electron flux dropouts in the magnetosphere
Authors: Gao Xinliang , Li Wen , Bortnik Jacob , Thorne Richard M. , Lu Quanming , Ma Qianli , Tao Xin , Wang Shui
Published: May 2015

Superposed epoch analyses were performed on 193 significant relativistic electron flux dropout events, in order to study the roles of different solar wind parameters in driving the depletion of relativistic electrons, using ~16 years of data from the POES and GOES missions, and the OMNIWEB solar wind database. We find that the solar wind dynamic pressure and interplanetary magnetic field (IMF) Bz play key roles in causing the relativistic electron flux dropouts, but also that either large solar wind dynamic pressure or strong southward IMF Bz by itself is capable of producing the significant depletion of relativistic electrons. The relativistic electron flux dropouts occur not only when the magnetopause is compressed closer to the Earth but also when the magnetopause is located very far (> ~10 RE). Importantly, our results show that in addition to the large solar wind dynamic pressure, which pushes the magnetopause inward strongly and causes the electrons to escape from the magnetosphere, relativistic electrons can also be scattered into the loss cone and precipitate into the Earth's atmosphere during periods of strong southward IMF Bz, which preferentially provides a source of free energy for electromagnetic ion cyclotron (EMIC) wave excitation. This is supported by the fact that the strongest electron precipitation into the atmosphere is found in the dusk sector, where EMIC waves are typically observed in the high‐density plasmasphere or plume and cause efficient electron precipitation down to ~1 MeV.
A data assimilation technique to account for the nonlinear dependence of scattering microwave observations of precipitation
Authors: Haddad Z. S. , Steward J. L. , Tseng H.‐C. , Vukicevic T. , Chen S.‐H. , Hristova‐Veleva S.
Published: May 2015

Satellite microwave observations of rain, whether from radar or passive radiometers, depend in a very crucial way on the vertical distribution of the condensed water mass and on the types and sizes of the hydrometeors in the volume resolved by the instrument. This crucial dependence is nonlinear, with different types and orders of nonlinearity that are due to differences in the absorption/emission and scattering signatures at the different instrument frequencies. Because it is not monotone as a function of the underlying condensed water mass, the nonlinearity requires great care in its representation in the observation operator, as the inevitable uncertainties in the numerous precipitation variables are not directly convertible into an additive white uncertainty in the forward calculated observations. In particular, when attempting to assimilate such data into a cloud‐permitting model, special care needs to be applied to describe and quantify the expected uncertainty in the observations operator in order not to turn the implicit white additive uncertainty on the input values into complicated biases in the calculated radiances. One approach would be to calculate the means and covariances of the nonlinearly calculated radiances given an a priori joint distribution for the input variables. This would be a very resource‐intensive proposal if performed in real time. We propose a representation of the observation operator based on performing this moment calculation off line, with a dimensionality reduction step to allow for the effective calculation of the observation operator and the associated covariance in real time during the assimilation. The approach is applicable to other remotely sensed observations that depend nonlinearly on model variables, including wind vector fields. The approach has been successfully applied to the case of tropical cyclones, where the organization of the system helps in identifying the dimensionality‐reducing variables.
Metallic Fuels
Authors: Hofman Gerard L.
Published: May 2015

The article contains sections titled:

Introduction

Irradiation Behavior

Swelling and Gas Release

Uranium

Uranium–Plutonium

Thorium–Uranium (Plutonium)

Alloys with Nonfissile and Nonfertile Constituents

Alloys Containing Minor Actinides

U–Pu–ZrAlloy Fuels for Fast Reactors

Fuel–Cladding Interaction

Fuel–Cladding Mechanical Interaction

Fission‐Induced Creep

Fuel–Cladding Chemical Interaction

Transient Testing

Operation of Fuel Elements with Breached Cladding
Survival outcomes of secondary cancers in patients with waldenström macroglobulinemia: An analysis of the SEER database
Authors: Castillo Jorge J. , Olszewski Adam J. , Kanan Sandra , Meid Kirsten , Hunter Zachary R. , Treon Steven P.
Published: May 2015

We hypothesized that survival outcomes of WM patients who develop SM is distinct from the general population of individuals who develop those same malignancies. Using the SEER‐18 data (2000–2011), we identified patients with cancers of the breast, prostate, lung, colorectum, bladder, melanoma, non‐Hodgkin lymphoma (NHL), and acute leukemia, and compared their outcomes according to having antecedent WM or not. The outcome of interest was overall survival (OS), which was analyzed in proportional‐hazard models adjusted for age, sex, race, and stage. We found that patients with WM who developed SM were older than population controls with those same cancers. In the multivariate analysis, WM cases with colorectal cancer (HR 1.97; P < 0.001), melanoma (HR 2.63; P < 0.001) and NHL (HR = 1.35; P = 0.02) had worse OS than controls with those respective cancers. WM patients with diffuse large B‐cell lymphoma also had worse OS (HR = 1.86; P = 0.008). The utilization of surgery and radiation was similar between WM cases and controls, except lower rates of prostatectomy and melanoma surgery among WM patients. The survival of WM patients with colorectal cancer, melanoma, and NHL is worse than among general population controls, arguing in favor of age‐appropriate cancer screening. Am. J. Hematol. 90:696–701, 2015. © 2015 Wiley Periodicals, Inc.
A Versatile Approach for the Site‐Specific Modification of Recombinant Antibodies Using a Combination of Enzyme‐Mediated Bioconjugation and Click Chemistry
Authors: Alt Karen , Paterson Brett M. , Westein Erik , Rudd Stacey E. , Poniger Stan S. , Jagdale Shweta , Ardipradja Katie , Connell Timothy U. , Krippner Guy Y. , Nair Ashish K. N. , Wang Xiaowei , Tochon‐Danguy Henri J. , Donnelly Paul S. , Peter Karlheinz , Hagemeyer Christoph E.
Published: May 2015

A unique two‐step modular system for site‐specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for incorporation of strained cyclooctyne functional groups. The second step of this modular approach involves the azide–alkyne cycloaddition click reaction. The versatility of the two‐step approach has been exemplified by the selective incorporation of fluorescent dyes and a positron‐emitting copper‐64 radiotracer for fluorescence and positron‐emission tomography imaging of activated platelets, platelet aggregates, and thrombi, respectively. This flexible and versatile approach could be readily adapted to incorporate a large array of tailor‐made functional groups using reliable click chemistry whilst preserving the activity of the antibody or other sensitive biological macromolecules.
Nano‐sio2‐reinforced ultraviolet‐curing materials for three‐dimensional printing
Authors: Zhang Congchao , Cui Yihua , Li Juan , Jiang Dandan
Published: May 2015

As an additive manufacturing technology, ultraviolet (UV)‐curing three‐dimensional printing, which requires the use of a photocurable resin, is increasingly being used to produce customized end‐user parts of many complex shapes. In this study, to improve the strength and ductility of printing materials, nano‐SiO2‐reinforced photocurable resins were prepared by a planetary ball mill; then, the morphology, photochemistry, thermal property, and mechanical properties of the nanocomposites were investigated and characterized. Transmission electron microscopy analysis indicated that the modified nano‐SiO2 was well dispersed in the photocurable resin. The glass‐transition temperature increased from 67.2°C for the unfilled resin to 71.7 and 80.1°C for nanocomposites with nano‐SiO2 contents of 0.3 and 0.7 wt %, respectively. The tensile strength and impact strength were increased by 46.7 and 165.3% for nanocomposites with 0.3 wt % nano‐SiO2. The flexural modulus of the nanocomposites increased from 1.7 to 8.0 GPa when 0.7 wt % nano‐SiO2 was added to the photocurable resin; this appeared to originate from the relatively high level of dispersion and the intimate combination of the nano‐SiO2 with the matrix. The investigation of the physical and chemical properties of such UV‐curing materials showed that the low filler concentration (<1 wt %) of nano‐SiO2 did not affect the processability of the nanocomposites. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42307.
Biodegradable antimicrobial films based on poly(lactic acid) matrices and active azo compounds
Authors: Concilio Simona , Iannelli Pio , Sessa Lucia , Olivieri Rita , Porta Amalia , De Santis Felice , Pantani Roberto , Piotto Stefano
Published: May 2015

Using solvent casting and melt compounding methods, we realized antibacterial and antifungal poly(lactic acid)‐based films by introducing different percentages of antimicrobial azo dyes into polymer matrices. Concentration up to 0.01% (w/w) of azo compounds permitted the preparation of antimicrobial and transparent films. The thin films retained the properties of the pure PLA matrices, such as glass transition temperature, flexibility, and amorphous nature. The films exhibited antimicrobial activity and the capability to inhibit biofilms formation of Staphylococcus aureus and Candida albicans. Spectrophotometric investigation of azo compounds release from the polymer matrices confirmed that the materials might have applications in fields where an intrinsic antimicrobial ability of the material is required, such as biomedical tools, biodegradable antibacterial coatings, and films for active packaging. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42357.
Attachment ability of two invasive amphipod species may promote their spread by overland transport
Authors: Bacela‐Spychalska K.
Published: May 2015

Amphipods are very successful invaders in European inland waters including lakes.

There are several vectors identified as responsible for amphipod species introductions and spread, with overland transport increasingly recognized as particularly important, especially in conjunction with transport between sites of sailing and/or angling activity.

In this study two species of invasive gammarids with a wide distribution range in Europe, Dikerogammarus haemobaphes and Pontogammarus robustoides, were tested for their ability to attach and remain adhered to sailing rope.

The results of the experiment show that both species may have high potential to be transported with sailing/angling equipment, as the percentage of individuals remaining attached to the rope after 30 s of ‘holding’ followed by 30 s of ‘shaking’ was very high (24% and 17%, for D. haemobaphes and P. robustoides, respectively).

The necessity for preventative measures to stop translocation of these species between European water bodies is emphasized and discussed.

Copyright © 2015 John Wiley & Sons, Ltd.
Verapamil hepatic clearance in four preclinical rat models: towards activity‐based scaling
Authors: Nicolaï J. , De Bruyn T. , Van Veldhoven P. P. , Keemink J. , Augustijns P. , Annaert P.
Published: May 2015

The current study was designed to cross‐validate rat liver microsomes (RLM), suspended rat hepatocytes (SRH) and the isolated perfused rat liver (IPRL) model against in vivo pharmacokinetic data, using verapamil as a model drug. Michaelis‐Menten constants (Km), for the metabolic disappearance kinetics of verapamil in RLM and SRH (freshly isolated and cryopreserved), were determined and corrected for non‐specific binding. The ‘unbound’ Km determined with RLM (2.8 µ m) was divided by the ‘unbound’ Km determined with fresh and cryopreserved SRH (3.9 µ m and 2.1 µ m, respectively) to calculate the ratio of intracellular to extracellular unbound concentration (Kpu,u). Kpu,u was significantly different between freshly isolated (0.71) and cryopreserved (1.31) SRH, but intracellular capacity for verapamil metabolism was maintained after cryopreservation (200 vs. 191 µl/min/million cells). Direct comparison of intrinsic clearance values (Clint) in RLM versus SRH, yielded an activity‐based scaling factor (SF) of 0.28–0.30 mg microsomal protein/million cells (MPPMC). Merging the IPRL‐derived Clint with the MPPMC and SRH data, resulted in scaling factors for MPPGL (80 and 43 mg microsomal protein/g liver) and HPGL (269 and 153 million cells/g liver), respectively. Likewise, the hepatic blood flow (61 ml/min/kg b.wt) was calculated using IPRL Clint and the in vivo Cl. The scaling factors determined here are consistent with previously reported CYP450‐content based scaling factors. Overall, the results show that integrated interpretation of data obtained with multiple preclinical tools (i.e. RLM, SRH, IPRL) can contribute to more reliable estimates for scaling factors and ultimately to improved in vivo clearance predictions based on in vitro experimentation. Copyright © 2015 John Wiley & Sons, Ltd.
Rapid method for thermal dose‐based safety supervision during MR scans
Authors: Neufeld Esra , Fuetterer Maximilian , Murbach Manuel , Kuster Niels
Published: May 2015

To maximize diagnostic accuracy and minimize costs, magnetic resonance imaging (MRI) scanners expose patients to electromagnetic exposure levels well above the established maximum, but in a well‐controlled environment. In this paper, we discuss a novel safety assessment model that offers maximum flexibility while ensuring no local tissue damage due to radiofrequency induced heating occurs. This model is based on the cumulative equivalent minutes at 43 °C (CEM43) thermal dose concept, which naturally considers exposure duration, tissue sensitivity and the transient nature of heating, and permits rapid assessment of exposure safety of a given MRI scan using information about the transient specific absorption rate (SAR). It builds upon theoretical considerations (e.g., relating peak temperatures in the presence and absence of local thermoregulation) as well as data extracted from simulations involving anatomical models (e.g., to determine the characteristic time of temperature changes). The model is capable of predicting CEM43 for patients with either uncompromised thermoregulation or absent thermoregulation. The model predictions approximate detailed simulations well and results illustrate the importance of adequately considering changes in perfusion. The model presented herein offers an MRI safety assessment approach that overcomes problems associated with traditional SAR‐based limits. Its limitations and the associated uncertainties are discussed together with remaining open questions. Bioelectromagnetics. 36:398–407, 2015. © 2015 Wiley Periodicals, Inc.
Micelle‐Enhanced Bioorthogonal Labeling of Genetically Encoded Azido Groups on the Lipid‐Embedded Surface of a GPCR
Authors: Tian He , Sakmar Thomas P. , Huber Thomas
Published: May 2015

Genetically encoded p‐azido‐phenylalanine (azF) residues in G protein‐coupled receptors (GPCRs) can be targeted with dibenzocyclooctyne‐modified (DIBO‐modified) fluorescent probes by means of strain‐promoted [3+2] azide–alkyne cycloaddition (SpAAC). Here we show that azF residues situated on the transmembrane surfaces of detergent‐solubilized receptors exhibit up to 1000‐fold rate enhancement relative to azF residues on water‐exposed surfaces. We show that the amphipathic moment of the labeling reagent, consisting of hydrophobic DIBO coupled to hydrophilic Alexa dye, results in strong partitioning of the DIBO group into the hydrocarbon core of the detergent micelle and consequently high local reactant concentrations. The observed rate constant for the micelleenhanced SpAAC is comparable with those of the fastest bioorthogonal labeling reactions known. Targeting hydrophobic regions of membrane proteins by use of micelle‐enhanced SpAAC should expand the utility of bioorthogonal labeling strategies.
Outcomes of transcatheter aortic valve replacement in patients with chronic liver disease
Authors: Shah Anoop M. , Ogbara Jeffrey , Herrmann Howard C. , Fox Zachary , Kadakia Mitul , Anwaruddin Saif , Bavaria Joseph E. , Desai Nimesh D. , Jagasia Dinesh , Szeto Wilson Y. , Li Robert H. , Vallabhajosyula Prashanth , Giri Jay
Published: May 2015

Objective

Transcatheter aortic valve replacement (TAVR) has emerged as an alternative to high‐risk surgery in patients with comorbid conditions. The role of TAVR in patients with liver disease has not been examined.

Methods

We examined the procedural and intermediate to long‐term follow‐up outcomes of patients with severe symptomatic aortic valve stenosis and chronic liver disease, identified by liver biopsy or from a combination of clinical findings. All patients were treated with balloon‐expandable transfemoral (TF) or transapical (TA) TAVR between November 2007 and February 2014.

Results

A total of 17 of 706 (2.41%) patients treated at our institution with TF [n = 14] or TA [n = 3] TAVR had chronic liver disease (mean age 77.65 ± 9.06 years, 7 women, mean STS score 8.37, mean Charlson score 5.00, mean MELD score 11.35, Child–Turcotte–Pugh (CTP) Class A [n = 11], B [n = 6], C [n = 0], biopsy proven liver disease [n = 5]). Median follow‐up was 466 days (range = 12–1,403 days). The mean post‐procedure length of hospital stay was 5.88 ± 3.08 days. Procedural success was achieved in all cases. In‐hospital mortality was 5.88% and 90‐day mortality was 17.65%. Safety and efficacy endpoints as defined by the valve academic research consortium (VARC) were significant for one perioperative death from a proximate cardiac cause (post‐operative day 14), one death after hospital discharge of unknown cause (post‐operative day 12), two late deaths from non‐cardiac causes (post‐operative days 50 and 487, respectively), and one late death of unknown cause (post‐operative day 1,005). There were no life‐threatening or major bleeding complications. One patient had an MI, one had a transient ischemic attack, four had transient, Stage I, acute kidney injury and one had transient, Stage II, acute kidney injury.

Conclusion

TF and TA TAVR are feasible methods for treating aortic stenosis in patients with chronic liver disease. In patients with mild to moderate chronic liver disease there are acceptable rates of early and late complications, however, outcomes in patients with advanced liver disease (MELD >20 or CTP class C) warrant further study. © 2015 Wiley Periodicals, Inc.
Vascular brachytherapy versus drug‐eluting stents in the treatment of in‐stent restenosis: A meta‐analysis of long‐term outcomes
Authors: Benjo Alexandre , Cardoso Rhanderson N. , Collins Tyrone , Garcia Daniel , Macedo Francisco Y. , El‐Hayek Georges , Nadkarni Girish , Aziz Emad , Jenkins J. Stephen
Published: May 2015

Introduction

Clinical trials have shown a short‐term benefit of drug‐eluting stents (DES) compared to vascular brachytherapy (VBT) for treatment of in‐stent restenosis (ISR). The long‐term benefits of DES vs. VBT are conflicting in the literature. This study aimed to do a meta‐analysis of long‐term outcomes of DES compared to VBT for treatment of ISR.

Methods

PubMed, EMBASE, Cochrane Central and unpublished data were searched for cohort studies and randomized controlled trials (RCTs) that directly compared VBT to DES for the treatment of ISR. We evaluated the following outcomes at 2–5 years of follow‐up: target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), stent thrombosis, cardiovascular (CV) mortality, and overall mortality. Heterogeneity was defined as I2 values > 25%. Review Manager 5.1 was used for statistical analysis.

Results

We included 1,375 patients from five studies, of which three were RCTs. VBT was used to treat ISR in 685 (49.8%) patients. After a 2–5 year follow‐up, no significant differences were found between treatment groups regarding MI (P = 0.49), stent thrombosis (P = 0.86), CV mortality (P = 0.35), and overall mortality (P = 0.71). TLR (OR 2.37; CI 1.55–3.63; P < 0.001) and TVR (OR 2.23; CI 1.01–4.94; P = 0.05) were significantly increased in patients who received VBT.

Conclusion

This study suggests that DES are associated with decreased long‐term revascularization procedures when compared to VBT for the treatment of ISR. This benefit does not appear to be associated with a significant reduction in mortality or myocardial infarction. © 2015 Wiley Periodicals, Inc.
Midterm clinical outcome following Edwards SAPIEN or Medtronic Corevalve transcatheter aortic valve implantation (TAVI): Results of the Belgian TAVI registry
Authors: Collas Valérie M. , Dubois Christophe , Legrand Victor , Kefer Joëlle , De Bruyne Bernard , Dens Jo , Rodrigus Inez E. , Herijgers Paul , Bosmans Johan M. ,   for the Belgian TAVI Registry Participants
Published: May 2015

Objective

To assess midterm (3 years) clinical outcomes of transcatheter aortic valve implantation (TAVI) in Belgium using the Edwards SAPIEN valve or the Medtronic CoreValve transcatheter heart valve (THV).

Background

Medium and long term follow‐up data of both THVs are still relatively scarce, although of great clinical relevance for a relatively new but rapidly expanding treatment modality. Therefore, reporting mid‐ and long term clinical outcome data, coming from large “real world” national registries, remains contributive.

Methods

Between December 2007 and March 2012, 861 “real world” patients who were not candidates for surgical aortic valve replacement as decided by the local heart teams, underwent TAVI at 23 sites. Eleven sites exclusively used SAPIEN THV (n = 460), while 12 exclusively used CoreValve THV (n = 401). Differences in clinical outcomes by valve system were assessed, according to access route and baseline EuroSCORE risk profile (<10%: low, 10–20%: intermediate and >20%: high risk).

Results

Overall cumulative survival at 3 years was 51% for SAPIEN vs. 60% for CoreValve (P = 0.021). In transfemorally treated patients, SAPIEN and CoreValve had similar survival at 3 years for each of the baseline EuroSCORE cohorts (low risk: 72% vs. 76%, P = 0.45; intermediate risk: 62% vs. 59%, P = 0.94; high risk: 48% vs. 53%, P = 0.65).

Conclusion

Cumulative midterm 3 year survival after transfemoral TAVI in “real world” patients refused for surgery with similar baseline EuroSCORE risk profile is not different between SAPIEN or CoreValve. © 2015 Wiley Periodicals, Inc.
Sequential percutaneous closure of mitral prosthetic paravalvular leak and complex communicating pseudoaneurysms of the ascending aorta and subvalvar left ventricular outflow tract
Authors: Tretter Justin T. , Latson Larry A. , McElhinney Doff B.
Published: May 2015

Ascending aortic and subvalvar left ventricular outflow tract (LVOT) pseudoaneurysms are rare complications following aortic valve or root replacement surgery. Clinically important paravalvular leaks are rare complications following any valve replacement surgery. We report an unusual case of sequential percutaneous closure of mitral prosthetic paravalvular leak and complex communicating ascending aortic and subvalvar LVOT pseudoaneurysms, which demonstrates the importance of multimodal imaging assessment surrounding percutaneous closure. © 2015 Wiley Periodicals, Inc.
Hybrid Conducting Biofilm with Built‐in Bacteria for High‐Performance Microbial Fuel Cells
Authors: Zhao Cui‐e , Wu Jiansheng , Ding Yuanzhao , Wang Victor Bochuan , Zhang Yingdan , Kjelleberg Staffan , Loo Joachim Say Chye , Cao Bin , Zhang Qichun
Published: May 2015

The front cover artwork is provided by the group of Qichun Zhang at Nanyang Technology University (Singapore). The image shows the extracellular electron transfer between a graphene–carbon nanotube hybrid biofilm anode and­ Shewanella oneidensis­ cells. Read the full text of the Communication at10.1002/celc.201402458.
Microfoundations of institutional change: Contrasting institutional sabotage to entrepreneurship
Authors: Lakshman C. , Akhter Manzoom
Published: May 2015

This paper addresses little understood microfoundations of institutionally driven organizational change and utilizes an institutional‐conflict‐based approach to examine innovation in organizational forms. Using a two‐case comparative analysis, we longitudinally examine the antecedents, mechanisms, and success/failure of attempts at change by institutional entrepreneurs. We analyze and develop theoretical insights on the interplay between internal political processes and external competitive actions in the creation of innovation in organizational forms and the subsequent legitimacy struggles through which an organizational field evolves in a sports (cricket) business context. We draw implications for institutional actors by observing patterns in organizational and institutional evolution in such contexts. We contribute to institutional entrepreneurship literature by developing a nuanced process model of success and failure in institutional entrepreneurship. Copyright © 2015 ASAC. Published by John Wiley & Sons, Ltd.
Enhanced External Counterpulsation Is Cost‐Effective in Reducing Hospital Costs in Refractory Angina Patients
Authors: Lawson William E. , Hui John C.K. , Kennard Elizabeth D. , Linnemeier Georgiann ,   for the IEPR‐II Investigators
Published: May 2015

Background

Enhanced external counterpulsation (EECP) is effective in the treatment of refractory angina, a condition suffered by 1.7 million Americans. Declining cardiovascular mortality and appropriate use criteria may further increase this number.

Hypothesis

EECP is hypothesized to be cost‐effective in reducing hospitalizations in refractory angina patients.

Methods

The data used in this analysis were collected in phase II of the International EECP Patient Registry (IEPR‐II). Data were collected on changes in Canadian Cardiovascular Society functional class, Duke Activity Status Index, and number of hospitalizations in the 6 months prior to EECP and in the 6‐ and 12‐month intervals following EECP. Estimates of the changes in annual cost of all‐cause hospitalization before and after EECP therapy were calculated by the product of the differences in hospitalization rates in the 6‐month interval before and after EECP treatment and estimated hospitalization and physician charges after subtracting the average cost of EECP.

Results

Data for 1015 patients were analyzed. Hospitalization occurred in 55.2% of patients, an average of 1.7 ± 1.4 hospitalizations/patient, in the 6‐month period before 35 hours of EECP; and in 24.4%, an average of 1.4 ± 1.0 hospitalizations/patient, during the 6‐ to 12‐month period after EECP. The average hospitalization and physician charge in the US was $17 995, and the average EECP cost was $4880, yielding an annual cost savings/patient of $17 074.

Conclusions

Treatment of refractory angina patients with EECP resulted in improvement in angina and functional class accompanied by a sustained reduction in health care costs over 1 year of follow‐up.
Quality of Anticoagulation With Vitamin K Antagonists
Authors: Bertomeu‐González Vicente , Anguita Manuel , Moreno‐Arribas José , Cequier Ángel , Muñiz Javier , Castillo‐Castillo Jesús , Sanchis Juan , Roldán Inmaculada , Marin Francisco , Bertomeu‐Martínez Vicente ,   on behalf of the FANTASIIA Study Investigators
Published: May 2015

Background

Vitamin K antagonists (VKA) have a narrow therapeutic range, and literature analysis reveals poor quality of anticoagulation control. We sought to assess the prevalence of poor anticoagulant control in patients under VKA treatment in the prevention of stroke for atrial fibrillation (AF).

Hypothesis

Control of anticoagulation with VKA is inadequate in a high percentage of patients with AF.

Methods

Patients with AF under VKA treatment were prospectively recruited in this observational registry. The sample comprised 948 patients. The estimated time spent in the therapeutic range (TTR) was calculated, and variables related with a TTR >65% were analyzed.

Results

Mean age was 73.8 ± 9.4 years, and 42.5% of the patients were women. Mean TTR was 63.77% ± 23.80% for the direct method and 60.27% ± 24.48% for the Rosendaal method. Prevalence of poor anticoagulation control was 54%. Variables associated with good anticoagulation control were university studies (odds ratio [OR]: 1.99, 95% confidence interval [CI]: 1.08‐3.64), chronic hepatic disease (OR: 8.15, 95% CI: 1.57‐42.24), low comorbidity expressed as Charlson index (OR: 0.87, 95% CI: 0.76‐0.99), no previous cardiac disease (OR: 0.64, 95% CI: 0.41‐0.98), lower risk of bleeding assessed as hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly age, and use of drugs or alcohol (HAS‐BLED; OR: 0.81, 95% CI: 0.69‐0.95), and lower heart rate (OR: 0.99, 95% CI: 0.98‐0.99).

Conclusions

Patients who receive VKA to prevent stroke for AF spend less than half the time within therapeutic range.
Environmental Transmission Electron Microscopy Study of Diesel Carbon Soot Combustion under Simulated Catalytic‐Reaction Conditions
Authors: Mori Kohsuke , Watanabe Keitaro , Sato Takeshi , Yamashita Hiromi
Published: May 2015

The front cover artwork is provided by the groups of Prof. Kohsuke Mori and Prof. Hiromi Yamashita (Osaka University) in collaboration with Keitaro Watanabe and Dr. Takeshi Sato (Hitachi High‐Technologies). The cover picture shows the time‐lapsed TEM images acquired by environmental transmission electron microscopy (ETEM) observation during the exposure of the catalysts and soot to O2 at elevated temperatures. Read the full text of the article at 10.1002/cphc.201402818.
Cardiovascular Risk in Diabetes Mellitus: Complication of the Disease or of Antihyperglycemic Medications
Authors: Alvarez CA , Lingvay I , Vuylsteke V , Koffarnus RL , McGuire DK
Published: May 2015

Cardiovascular disease is the principal complication and the leading cause of death for patients with diabetes (DM). The efficacy of antihyperglycemic treatments on cardiovascular disease risk remains uncertain. Cardiovascular risk factors are affected by antihyperglycemic medications, as are many intermediate markers of cardiovascular disease. Here we summarize the evidence assessing the cardiovascular effects of antihyperglycemic medications with regard to risk factors, intermediate markers of disease, and clinical outcomes.
A Strengths Approach to Elder Mediation
Authors: Martin Jennifer
Published: May 2015

Elder mediators require specialist knowledge of aging in context, capacity, and dementia as well as skills in strategic intervention to redress power imbalances without jeopardizing mediator neutrality and the integrity of the mediation process. A review of the literature on the social context of aging highlights problems faced by older people. It is argued that a strengths approach facilitates critical reflection on issues of stigma, discrimination, and power imbalances. A focus on positive aspects of aging is emphasized promoting an encouraging environment for older people and family members to engage effectively in the mediation process.