bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolution of solar wind strahl with heliospheric distance
Authors: Graham G. A. , Rae I. J. , Owen C. J. , Walsh A. P. , Arridge C. S. , Gilbert L. , Lewis G. R. , Jones G. H. , Forsyth C. , Coates A. J. , Waite J. H.
Published: March 2017

Field‐aligned beams of suprathermal electrons, known as “strahl,” are a frequently observed constituent of solar wind plasma. However, the formation and interplanetary evolution of the strahl electron populations has yet to be fully understood. As strahl electrons travel away from the Sun, they move into regions of decreasing magnetic field strength and thus are subject to adiabatic focusing. However, the widths of strahl pitch angle distributions observed at 1 AU are significantly broader than expected. Previous investigations have found that the average observed strahl pitch angle width actually increases with heliocentric radial distance. This implies that strahl electrons must be subjected to some form of pitch angle scattering process or processes, details of which as of yet remain elusive. In this paper, we use Cassini electron measurements to examine strahl beams across a distance range of approximately 8 AU, from its Earth Flyby in 1999 until its insertion into orbit around Saturn in 2004. We find that, in general, there is a relatively constant rate of broadening of strahl pitch angle distributions with distance between ∼1 and 5.5 AU. Our results from beyond this distance indicate that the strahl population is likely to be completely scattered, presumably to form part of the halo. We find multiple energy dependences at different radial distances implying that there are multiple strahl scattering mechanisms in operation.
On nonhydrostatic coastal model simulations of shear instabilities in a stratified shear flow at high Reynolds number
Authors: Zhou Zheyu , Yu Xiao , Hsu Tian‐Jian , Shi Fengyan , Rockwell Geyer W. , Kirby James T.
Published: March 2017

The nonhydrostatic surface and terrain‐following coastal model NHWAVE is utilized to simulate a continually forced stratified shear flow in a straight channel, which is a generic problem to test the existing nonhydrostatic coastal models' capability in resolving shear instabilities in the field scale. The resolved shear instabilities in the shear layer has a Reynolds number of about 1.4 × 106, which is comparable to field observed value. Using the standard Smagorinsky closure with a grid size close to the Ozmidov length scale, simulation results show that the resolved energy cascade exceeds 1 order of magnitude and the evolution and turbulent mixing characteristics are predicted well. Two different approaches are used to estimate the turbulent dissipation rate, namely using the resolved turbulent energy spectrum and the parameterized subgrid turbulent dissipation rate, and the predicted results provide the upper and lower bounds that encompass the measured values. Model results show significantly higher turbulence in braids of shear instabilities, which is similar to field observations while both the subgrid turbulent dissipation rate and resolved vorticity field can be used as surrogates for measured high acoustic backscatter signals. Simulation results also reveal that the surface velocity divergence/convergence is an effective identifier for the front of the density current and the shear instabilities. To guide future numerical studies in more realistic domains, an evaluation on the effects of different grid resolutions and subgrid viscosity on the resolved flow field and subgrid dissipation rate are discussed.
Thin ice and storms: Sea ice deformation from buoy arrays deployed during N‐ICE2015
Authors: Itkin Polona , Spreen Gunnar , Cheng Bin , Doble Martin , Girard‐Ardhuin Fanny , Haapala Jari , Hughes Nick , Kaleschke Lars , Nicolaus Marcel , Wilkinson Jeremy
Published: March 2017

Arctic sea ice has displayed significant thinning as well as an increase in drift speed in recent years. Taken together this suggests an associated rise in sea ice deformation rate. A winter and spring expedition to the sea ice covered region north of Svalbard–the Norwegian young sea ICE2015 expedition (N‐ICE2015)—gave an opportunity to deploy extensive buoy arrays and to monitor the deformation of the first‐year and second‐year ice now common in the majority of the Arctic Basin. During the 5 month long expedition, the ice cover underwent several strong deformation events, including a powerful storm in early February that damaged the ice cover irreversibly. The values of total deformation measured during N‐ICE2015 exceed previously measured values in the Arctic Basin at similar scales: At 100 km scale, N‐ICE2015 values averaged above 0.1 d−1, compared to rates of 0.08 d−1 or less for previous buoy arrays. The exponent of the power law between the deformation length scale and total deformation developed over the season from 0.37 to 0.54 with an abrupt increase immediately after the early February storm, indicating a weakened ice cover with more free drift of the sea ice floes. Our results point to a general increase in deformation associated with the younger and thinner Arctic sea ice and to a potentially destructive role of winter storms.
Surface wave breaking over sheared currents: Observations from the Mouth of the Columbia River
Authors: Zippel Seth , Thomson Jim
Published: March 2017

Measurements of waves and currents from freely drifting buoys are used to evaluate wave breaking parameterizations at the Mouth of the Columbia River, where breaking occurs in intermediate depths and in the presence of vertically sheared currents. Breaking waves are identified using images collected with cameras onboard the buoys, and the breaking activity is well‐correlated with wave steepness. Vertical shear in the currents produces a frequency‐dependent effective current that modifies the linear dispersion relation. Accounting for these sheared currents in the wavenumber spectrum is essential in calculating the correct wave steepness; without this, wave steepness can be over (under) estimated on opposing (following) currents by up to 20%. The observed bulk steepness values suggest a limiting value of 0.4. The observed fraction of breaking waves is in good agreement with several existing models, each based on wave steepness. Further, a semispectral model designed for all depth regimes also compares favorably with measured breaking fractions. In this model, the majority of wave breaking is predicted to occur in the higher frequency bands (i.e., short waves). There is a residual dependence on directional spreading, in which wave breaking decreases with increasing directional spread.
A new look at ocean ventilation time scales and their uncertainties
Authors: Fine Rana A. , Peacock Synte , Maltrud Mathew E. , Bryan Frank O.
Published: March 2017

A suite of eddy‐resolving ocean transient tracer model simulations are first compared to observations. Observational and model pCFC‐11 ages agree quite well, with the eddy‐resolving model adding detail. The CFC ages show that the thermocline is a barrier to interior ocean exchange with the atmosphere on time scales of 45 years, the measureable CFC transient, although there are exceptions. Next, model simulations are used to quantify effects on tracer ages of the spatial dependence of internal ocean tracer variability due to stirring from eddies and biases from nonstationarity of the atmospheric transient when there is mixing. These add to tracer age uncertainties and biases, which are large in frontal boundary regions, and small in subtropical gyre interiors. These uncertainties and biases are used to reinterpret observed temporal trends in tracer‐derived ventilation time scales taken from observations more than a decade apart, and to assess whether interpretations of changes in tracer ages being due to changes in ocean ventilation hold water. For the southern hemisphere subtropical gyres, we infer that the rate of ocean ventilation 26–27.2σθincreased between the mid‐1990s and the decade of the 2000s. However, between the mid‐1990s and the decade of the 2010s, there is no significant trend—perhaps except for South Atlantic. Observed age/AOU/ventilation changes are linked to a combination of natural cycles and climate change, and there is regional variability. Thus, for the future it is not clear how strong or steady in space and time ocean ventilation changes will be.
Observations of waves and currents during barrier island inundation
Authors: Engelstad A. , Ruessink B.G. , Wesselman D. , Hoekstra P. , Oost A. , van der Vegt M.
Published: March 2017

Overwash and inundation on barrier islands can transport sediment onshore, leading to vertical accretion. These processes could ensure barrier island growth in times of sea‐level rise, but wave and current fields during overwash and inundation are not well understood. Field data of water levels, waves, and currents were collected on a barrier island in the Netherlands to investigate the hydrodynamics during island inundation. Observations show that even in shallow water depths (<0.5 m) wave energy was not completely dissipated as waves propagated from the North Sea onshore. Additionally, locally generated wind waves entered the field area from the Wadden Sea and propagated offshore. Infragravity waves were an important part of the wave field, particularly onshore of the beach crest. They were observed to be onshore progressive and displayed a bore‐like shape when water depths were shallow. Wave breaking was the dominant dissipation mechanism for high‐frequency waves as well as for infragravity waves, which is in agreement with prior research on infragravity wave energy dissipation on mild sloping (closed‐boundary) beaches. A large‐scale offshore directed water‐level gradient between the Wadden Sea and the North Sea side, caused by elevated water levels in the Wadden Sea during the storms, frequently drove an offshore flow if it was large enough to exceed the cross‐shore gradient due to wave setup. In addition, elevated water levels in the Wadden Sea decreased current velocities due to a decrease in water‐level gradients. This study highlights the influence of back‐barrier processes on the hydrodynamics during inundation.
Dynamical reconstruction of the global ocean state during the Last Glacial Maximum
Authors: Kurahashi‐Nakamura Takasumi , Paul André , Losch Martin
Published: March 2017

The global ocean state for the modern age and for the Last Glacial Maximum (LGM) was dynamically reconstructed with a sophisticated data assimilation technique. A substantial amount of data including global seawater temperature, salinity (only for the modern estimate), and the isotopic composition of oxygen and carbon (only in the Atlantic for the LGM) were integrated into an ocean general circulation model with the help of the adjoint method, thereby the model was optimized to reconstruct plausible continuous fields of tracers, overturning circulation and water mass distribution. The adjoint‐based LGM state estimation of this study represents the state of the art in terms of the length of forward model runs, the number of observations assimilated, and the model domain. Compared to the modern state, the reconstructed continuous sea‐surface temperature field for the LGM shows a global‐mean cooling of 2.2 K, and the reconstructed LGM ocean has a more vigorous Atlantic meridional overturning circulation, shallower North Atlantic Deep Water (NADW) equivalent, stronger stratification, and more saline deep water.
Current challenges in monitoring, discrimination, and management of induced seismicity related to underground industrial activities: A European perspective
Authors: Grigoli Francesco , Cesca Simone , Priolo Enrico , Rinaldi Antonio Pio , Clinton John F. , Stabile Tony A. , Dost Bernard , Fernandez Mariano Garcia , Wiemer Stefan , Dahm Torsten
Published: March 2017

Due to the deep socioeconomic implications, induced seismicity is a timely and increasingly relevant topic of interest for the general public. Cases of induced seismicity have a global distribution and involve a large number of industrial operations, with many documented cases from as far back to the beginning of the twentieth century. However, the sparse and fragmented documentation available makes it difficult to have a clear picture on our understanding of the physical phenomenon and consequently in our ability to mitigate the risk associated with induced seismicity. This review presents a unified and concise summary of the still open questions related to monitoring, discrimination, and management of induced seismicity in the European context and, when possible, provides potential answers. We further discuss selected critical European cases of induced seismicity, which led to the suspension or reduction of the related industrial activities.
What's Context Got to Do with It? Comparative Difficulty of Test Questions Influences Metacognition and Corrected Scores for Formula‐scored Exams
Authors: Arnold Michelle M. , Graham Kristin , Hollingworth‐Hughes Sinead
Published: March 2017

Summary: On formula‐scored exams students receive points and penalties for correct and incorrect answers, respectively, but they can avoid the penalty by withholding incorrect answers. However, test‐takers have difficulty strategically regulating their accuracy and often set an overly conservative metacognitive response bias (e.g., Higham, 2007). The current experiments extended these findings by exploring whether the comparative difficulty of surrounding test questions (i.e., easy vs. hard)—a factor unrelated to the knowledge being tested—impacts metacognitive response bias for medium‐difficulty test questions. Comparative difficulty had no significant influence on participants' ability to choose correct answers for medium questions, but it did affect willingness to report answers and confidence ratings. This difference carried over to corrected scores (scores after penalties are applied) when comparative difficulty was manipulated within‐subjects: Scores were higher in the hard condition. Results are discussed in terms of implications for interpreting formula‐scored tests and underlying mechanisms of performance.Copyright © 2017 John Wiley & Sons, Ltd.
Understanding the Individual Cognitive Potential of Persons with Intellectual Disability in Workshops for Adapted Work
Authors: Sebastian Katharina , Ghose Tandra , Zacks Jeffrey M. , Huff Markus
Published: March 2017

We aimed at using simple judgments of event segmentation to reveal cognitive problems in workers with intellectual disability regarding their assembly performance. We investigated event perception and assembly performance in 32 workers (mean IQ = 64.4). First, we assessed their ability to segment activity into meaningful events. The task involved segmenting four videos in coarse and fine events. We assessed event segmentation performance and compared it to 30 controls (IQ > 100). The workers detected fewer event boundaries than controls. A subgroup of the workers (12 of 32) defined more event boundaries in the coarse than the fine condition, indicating misconception of higher‐ and lower‐level content. The remaining 20 workers showed diminished hierarchical alignment compared to controls. Second, workers executed a Lego task. Better event segmentation performance was associated with enhanced assembly performance. These results suggest that the event segmentation task can serve as a diagnostic assessment for cognitive potential.Copyright © 2017 John Wiley & Sons, Ltd.
The Individual Depictive Style: Individual Differences in Narrating Personal Experiences
Authors: Heering Nina , Volbert Renate
Published: March 2017

This study aims to identify characteristic variables of individual narrative habits. A total of 59 participants each related three personal experiences of varying emotional valence. Their transcribed statements were coded for a range of linguistic and content‐related variables and aspects of narrative style. In addition, transcripts were analyzed by the computer program Linguistic Inquiry and Word Count. By definition, a variable was considered to be indicative of the individual depictive style when all paired correlations of the three statement conditions as well as the global measure of internal consistency were significant. Ten linguistic variables and eight Linguistic Inquiry and Word Count features met the predefined demands. Exploratory factor analyses were conducted to illuminate underlying cognitive mechanisms. The meaning of the results for deception detection is discussed: vague descriptions and overgeneralizations might be considered as indicators of deception; however, they may just be the expression of a stable individual narrative habit. Copyright © 2017 John Wiley & Sons, Ltd.
Effect of Grain Shape on Texture Formation during Severe Plastic Deformation of Pure Copper
Authors: Jahedi Mohammad , Beyerlein Irene J. , Paydar Mohammad Hossein , Knezevic Marko
Published: March 2017

In this study, the authors use a combination of electron backscattered diffraction and polycrystal plasticity modeling to study the effect of grain shape on texture development in high pressure torsion and high pressure double torsion in high purity Cu. With varying applied pressures and after a large amount of strain corresponding to two to four turns, the average aspect ratios of the grains has changed from being elongated under higher pressures to nearly equiaxed for lower pressures, while keeping the average grain size similar among all samples analyzed. Polycrystal modeling is used to help isolating the deformation effect from the grain shape effect. The authors show that grains with elongated shapes form shear textures with a predominant C component, whereas those with largely equiaxed grains possess conventional shear textures.
N‐, O‐, and S‐Tridoped Carbon‐Encapsulated Co9S8 Nanomaterials: Efficient Bifunctional Electrocatalysts for Overall Water Splitting
Authors: Huang Senchuan , Meng Yuying , He Shiman , Goswami Anandarup , Wu Qili , Li Junhao , Tong Shengfu , Asefa Tewodros , Wu Mingmei
Published: March 2017

The development of highly active and stable earth‐abundant catalysts to reduce or eliminate the reliance on noble‐metal based ones in green and sustainable (electro)chemical processes is nowadays of great interest. Here, N‐, O‐, and S‐tridoped carbon‐encapsulated Co9S8 (Co9S8@NOSC) nanomaterials are synthesized via simple pyrolysis of S‐ and Co(II)‐containing polypyrrole solid precursors, and the materials are proven to serve as noble metal‐free bifunctional electrocatalysts for water splitting in alkaline medium. The nanomaterials exhibit remarkable catalytic performances for oxygen evolution reaction in basic electrolyte, with small overpotentials, high anodic current densities, low Tafel slopes as well as very high (nearly 100%) Faradic efficiencies. Moreover, the materials are found to efficiently electrocatalyze hydrogen evolution reaction in acidic as well as basic solutions, showing high activity in both cases and maintaining good stability in alkaline medium. A two‐electrode electrolyzer assembled using the material synthesized at 900 °C (Co9S8@NOSC‐900) as an electrocatalyst at both electrodes gives current densities of 10 and 20 mA cm−2 at potentials of 1.60 and 1.74 V, respectively. The excellent electrocatalytic activity exhibited by the materials is proposed to be mainly due to the synergistic effects between the Co9S8 nanoparticles cores and the heteroatom‐doped carbon shells in the materials.
Reusable Cellulose‐Based Hydrogel Sticker Film Applied as Gate Dielectric in Paper Electrolyte‐Gated Transistors
Authors: Cunha Inês , Barras Raquel , Grey Paul , Gaspar Diana , Fortunato Elvira , Martins Rodrigo , Pereira Luís
Published: March 2017

A new concept for reusable eco‐friendly hydrogel electrolytes based on cellulose is introduced. The reported electrolytes are designed and engineered through a simple, fast, low‐cost, and eco‐friendly dissolution method of microcrystalline cellulose at low temperature using an aqueous LiOH/urea solvent system. The cellulose solution is combined with carboxymethyl cellulose, followed by the regeneration and simultaneous ion incorporation. The produced free standing cellulose‐based electrolyte films exhibit interesting properties for application in flexible electrochemical devices, such as biosensors or electrolyte‐gated transistors (EGTs), because of their high specific capacitances (4–5 µF cm−2), transparency, and flexibility. Indium–gallium–zinc‐oxide EGTs on glass with laminated cellulose‐based hydrogel electrolytes (CHEs) as the gate dielectric are produced presenting a low working voltage (<2 V), showing an on–off current ratio (Ion/off) of 106, a subthreshold swing lower than 0.2 V dec−1, and saturation mobility (μSat) reaching 26 cm2 V−1 s−1. The flexible CHE‐gated transistors on paper are also demonstrated, which operate at switching frequencies up to 100 Hz. Combining the flexibility of the EGTs on paper with the reusability of the developed CHEs is a breakthrough toward biodegradable advanced functional materials allied with disposable/recyclable and low‐cost electronic devices.
Multicellular Biohybrid Materials: Probing the Interplay of Cells of Different Types Precisely Positioned and Constrained on 3D Wireframe‐Like Microstructures
Authors: Gullo Maurizio R. , Takeuchi Shoji , Paul Oliver
Published: March 2017

Driven by the unbroken miniaturization trend in microtechnology, the development of smaller, yet reliable and efficient, highly integrated microsystems can benefit from inherent capabilities of biological cells. In particular, by featuring multiple types of cells, biohybrid systems exhibiting self‐contained sensing and actuation capabilities can be conceived. To ensure the proper functioning of such multicellular biohybrid systems, the intended cell arrangement needs to be maintained over time. Microscaffolds designed for this purpose should therefore selectively guide or hinder cell migration. However, the basic cell‐structure interactions governing the cell migration and extension processes are not yet fully understood. This paper explores these interactions and proposes a method for the fabrication of advanced multicellular biohybrid materials. The method is based on wireframe‐like 3D microstructures onto which several types of cells are successfully positioned and arranged by optical manipulation. Experiments exploring cell dynamics reveal geometry‐dependent maximal migration and extension distances. Microscaffolds designed on the basis of these characteristics can guide cell migration, trigger structure‐contained cell growth, and maintain a predetermined cell arrangement. The methods reported herein therefore provide insight into cell assembly and migration on 3D microscaffolds, which is an essential early step towards advanced multicellular biohybrid materials.
Construction of Small‐Diameter Vascular Graft by Shape‐Memory and Self‐Rolling Bacterial Cellulose Membrane
Authors: Li Ying , Jiang Kai , Feng Jian , Liu Jinzhe , Huang Rong , Chen Zhaojun , Yang Junchuan , Dai Zhaohe , Chen Yong , Wang Nuoxin , Zhang Wenjin , Zheng Wenfu , Yang Guang , Jiang Xingyu
Published: March 2017

Bacterial cellulose (BC) membranes with shape‐memory properties allow the rapid preparation of artificial small‐diameter blood vessels when combined with microfluidics‐based patterning with multiple types of cells. Lyophilization of a wet multilayered rolled BC tube endows it with memory to recover its tubular shape after unrolling. The unrolling of the BC tube yields a flat membrane, and subsequent patterning with endothelial cells, smooth muscle cells, and fibroblast cells is carried out by microfluidics. The cell‐laden BC membrane is then rerolled into a multilayered tube. The different cells constituting multiple layers on the tubular wall can imitate blood vessels in vitro. The BC tubes (2 mm) without cell modification, when implanted into the carotid artery of a rabbit, maintain thrombus‐free patency 21 d after implantation. This study provides a novel strategy for the rapid construction of multilayered small‐diameter BC tubes which may be further developed for potential applications as artificial blood vessels.
Effect of processing techniques on new poly(ε‐caprolactone)‐embelin microparticles of biomedical interest
Authors: Cortez Tornello Pablo R. , Feresin Gabriela E. , Tapia Alejandro , Dzieciuch Monika , Cuadrado Teresita R. , Abraham Gustavo A.
Published: March 2017

Poly(ε‐caprolactone) microparticles containing embelin (PCLE) are prepared by electrohydrodynamic atomization (EHDA) and emulsion‐solvent evaporation techniques. Microparticles are characterized in terms of drug state, drug‐loading capacity, encapsulation efficiency, morphology and in vitro release in different mediums. Physicochemical, morphological, and thermal characterization is presented. Kinetic analysis is performed. EHDA microparticles present higher size, surface area, and encapsulation efficiency. The release profiles combine a high initial release, followed by a slow‐controlled release stage. Electrosprayed PCLE presented characteristics such as size (3.14 ± 0.05 μm), zeta potential (−49.22 ± 2.88 mV) and release profiles that could be attractive for the development of microcarriers for pulmonary administration of embelin.
Solving Key Challenges in Battery Research Using In Situ Synchrotron and Neutron Techniques
Authors: Gu Qinfen , Kimpton Justin A. , Brand Helen E. A. , Wang Zhiyang , Chou Shulei
Published: March 2017

Understanding the electrochemical reaction mechanisms and kinetics in batteries is the key challenge for developing breakthroughs with new or existing electrode materials. X‐rays and neutrons are excellent probes for studying atomic structure changes and phase evolution in battery materials during charge and discharge. Synchrotron X‐ray powder diffraction (SXPD), with its high angular resolution and beam intensity, allows fast scattering and diffraction data collection to record crystalline structure changes that occur on short time‐scales. Neutron powder diffraction (NPD) provides complementary information that is sensitive to different structural details during charge/discharge. More recently X‐ray absorption spectroscopy (XAS) has been used to identify the oxidation states of transition metal ions present in new cathode compositions at different stages of battery cycling. Using in‐house designed battery cells, electrodes or other cell components can be subjected to conditions designed to mimic their real operating conditions. It is preferable to investigate battery materials in operation to identify any critical intermediate stages during charge/discharge rather than using ex situ methods to analyse dismantled batteries. Examples and combinations of SXPD, XAS, and NPD measurements, which have been used to investigate lithium ion batteries and sodium ion batteries, are described and reviewed in this contribution.
Carbon Anode Materials for Advanced Sodium‐Ion Batteries
Authors: Hou Hongshuai , Qiu Xiaoqing , Wei Weifeng , Zhang Yun , Ji Xiaobo
Published: March 2017

The ever‐increasing demand of lithium‐ion batteries (LIBs) caused by the rapid development of various electronics and electric vehicles will be hindered by the limited lithium resource. Thus sodium‐ion batteries (SIBs) have been considered as a promising potential alternative for LIBs owing to the abundant sodium resource and similar electrochemical performances. In recent years, significant achievements regarding anode materials which restricted the development of SIBs in the past decades have been attained. Significantly, the sodium storage feasibility of carbon materials with abundant resource, low cost, nontoxicity and high safety has been confirmed, and extensive investigation have demonstrated that the carbonaceous materials can become promising electrode candidates for SIBs. In this review, the recent progress of the sodium storage performances of carbonaceous materials, including graphite, amorphous carbon, heteroatom‐doped carbon, and biomass derived carbon, are presented and the related sodium storage mechanism is also summarized. Additionally, the critical issues, challenges and perspectives are provided to further understand the carbonaceous anode materials.
Targeted next generation sequencing and identification of risk factors in World Health Organization defined atypical chronic myeloid leukemia
Authors: Patnaik Mrinal M. , Barraco Daniela , Lasho Terra L. , Finke Christy M. , Reichard Kaaren , Hoversten Katherine P. , Ketterling Rhett P. , Gangat Naseema , Tefferi Ayalew
Published: March 2017

Atypical chronic myeloid leukemia (aCML) is an aggressive myeloid neoplasm with overlapping features of myelodysplastic syndromes (prominent granulocytic dysplasia) and myeloproliferative neoplasms (neutrophilic leukocytosis). We studied 25 molecularly‐annotated and World Health Organization defined aCML patients; median age 70 years, 84% males. Cytogenetic abnormalities were seen in 36% and gene mutations in 100%. Mutational frequencies were, ASXL1 28%, TET2 16%, NRAS 16%, SETBP1 12%, RUNX1 12%, ETNK1 8%, and PTPN11 4%. Fifteen patients (60%) had >1 mutation, while 9 (36%) had ≥3. The median overall survival (OS) was 10.8 months and at last follow up (median 11 months), 17 (68%) deaths and 2 (8%) leukemic transformations were documented. On univariate analysis, survival was adversely impacted by advanced age (P = .02), low hemoglobin (P = .01), red blood cell transfusion dependence (P = .03), high white blood cell count (P = .02), TET2 (P = .03), NRAS (P = .04), PTPN11 (P = .02) mutations and the presence of ≥3 gene mutations (P = .006); ASXL1, SETBP1, and ETNK1 mutations did not impact OS. In multivariable analysis, advanced age (P = .003) [age >67: HR 10.1, 95% CI 1.3‐119], low hemoglobin (P = .008) [HB< 10 gm/dL: HR 8.2, 95% CI 1.6‐23.2] and TET2 mutations (P = .01) [HR 8.8, 95% CI 1.6‐47.7] retained prognostic significance. We then used age >67 years, hemoglobin <10 gm/dL and the presence of TET2 mutations (each counted as one risk factor) to create a hazard ratio weighted prognostic model; effectively stratifying patients into two risk categories, low (0‐1 risk factor) and high (≥2 risk factors), with median OS of 18 and 7 months, respectively.
Treatment patterns and outcome following initial relapse or refractory disease in patients with systemic light chain amyloidosis
Authors: Tandon Nidhi , Sidana Surbhi , Gertz Morie A. , Dispenzieri Angela , Lacy Martha Q. , Buadi Francis K. , Dingli David , Fonder Amie L. , Hobbs Miriam A. , Hayman Suzanne R. , Gonsalves Wilson I. , Hwa Yi Lisa , Kapoor Prashant , Kyle Robert A. , Leung Nelson , Go Ronald S. , Lust John A. , Russell Stephen J. , Zeldenrust Steven R. , Rajkumar S. Vincent , Kumar Shaji K.
Published: March 2017

We analyzed the outcomes following initial relapse or refractory disease in systemic light chain amyloidosis (AL) and the impact of type of therapy employed.A total of 1327 patients with AL seen at Mayo Clinic within 90 days of diagnosis, between 2006 and 2015, were reviewed. The study included 366 patients experiencing a documented hematological or organ relapse or refractory disease requiring start of second line therapy. Overall survival (OS) and time to next treatment (TTNT) were calculated from start of second line treatment.The median time to require second line treatment was 16.2 months (1‐93) from the start of first line therapy. At relapse, patients received proteasome inhibitors (PI; 45.1%), immunomodulators (IMiD; 22.7%), alkylators (9%), PI and IMiD combination (4.1%), autologous transplant (3.8%), steroids and other therapies (4.9%). Among these, 124 (33.9%) required change or reinstitution of therapy. The median time to require third line treatment was 31 months (95% CI; 24, 40.5) and the median overall survival (OS) was 38.8 months (95% CI; 29.6, 52.6) from the start of second line treatment. Retreatment with same therapy at relapse significantly reduced TTNT (22 m vs 32.3 m; P = .01) as compared to different therapy; but did not have any impact OS (30.8 m vs 51.1 m; P = .5). In conclusion, this study provides important information about outcomes of patients with AL who require second line treatment for relapsed/refractory disease . Treatment with a different therapy at relapse improves time to next therapy but does not impact OS.
Measurement properties of clinical assessment methods for classifying generalized joint hypermobility—A systematic review
Authors: Juul‐Kristensen Birgit , Schmedling Karoline , Rombaut Lies , Lund Hans , Engelbert Raoul H. H.
Published: March 2017

The purpose was to perform a systematic review of clinical assessment methods for classifying Generalized Joint Hypermobility (GJH), evaluate their clinimetric properties, and perform the best evidence synthesis of these methods. Four test assessment methods (Beighton Score [BS], Carter and Wilkinson, Hospital del Mar, Rotes‐Querol) and two questionnaire assessment methods (Five‐part questionnaire [5PQ], Beighton Score‐self reported [BS‐self]) were identified on children or adults. Using the Consensus‐based Standards for selection of health Measurement Instrument (COSMIN) checklist for evaluating the methodological quality of the identified studies, all included studies were rated “fair” or “poor.” Most studies were using BS, and for BS the reliability most of the studies showed limited positive to conflicting evidence, with some shortcomings on studies for the validity. The three other test assessment methods lack satisfactory information on both reliability and validity. For the questionnaire assessment methods, 5PQ was the most frequently used, and reliability showed conflicting evidence, while the validity had limited positive to conflicting evidence compared with test assessment methods. For BS‐self, the validity showed unknown evidence compared with test assessment methods. In conclusion, following recommended uniformity of testing procedures, the recommendation for clinical use in adults is BS with cut‐point of 5 of 9 including historical information, while in children it is BS with cut‐point of at least 6 of 9. However, more studies are needed to conclude on the validity properties of these assessment methods, and before evidence‐based recommendations can be made for clinical use on the “best” assessment method for classifying GJH. © 2017 Wiley Periodicals, Inc.
The Ehlers–Danlos syndromes, rare types
Authors: Brady Angela F. , Demirdas Serwet , Fournel‐Gigleux Sylvie , Ghali Neeti , Giunta Cecilia , Kapferer‐Seebacher Ines , Kosho Tomoki , Mendoza‐Londono Roberto , Pope Michael F. , Rohrbach Marianne , Van Damme Tim , Vandersteen Anthony , van Mourik Caroline , Voermans Nicol , Zschocke Johannes , Malfait Fransiska
Published: March 2017

The Ehlers–Danlos syndromes comprise a clinically and genetically heterogeneous group of heritable connective tissue disorders, which are characterized by joint hypermobility, skin hyperextensibility, and tissue friability. In the Villefranche Nosology, six subtypes were recognized: The classical, hypermobile, vascular, kyphoscoliotic, arthrochalasis, and dermatosparaxis subtypes of EDS. Except for the hypermobile subtype, defects had been identified in fibrillar collagens or in collagen‐modifying enzymes. Since 1997, a whole spectrum of novel, clinically overlapping, rare EDS‐variants have been delineated and genetic defects have been identified in an array of other extracellular matrix genes. Advances in molecular testing have made it possible to now identify the causative mutation for many patients presenting these phenotypes. The aim of this literature review is to summarize the current knowledge on the rare EDS subtypes and highlight areas for future research. © 2017 Wiley Periodicals, Inc.
The 2017 international classification of the Ehlers–Danlos syndromes
Authors: Malfait Fransiska , Francomano Clair , Byers Peter , Belmont John , Berglund Britta , Black James , Bloom Lara , Bowen Jessica M. , Brady Angela F. , Burrows Nigel P. , Castori Marco , Cohen Helen , Colombi Marina , Demirdas Serwet , De Backer Julie , De Paepe Anne , Fournel‐Gigleux Sylvie , Frank Michael , Ghali Neeti , Giunta Cecilia , Grahame Rodney , Hakim Alan , Jeunemaitre Xavier , Johnson Diana , Juul‐Kristensen Birgit , Kapferer‐Seebacher Ines , Kazkaz Hanadi , Kosho Tomoki , Lavallee Mark E. , Levy Howard , Mendoza‐Londono Roberto , Pepin Melanie , Pope F. Michael , Reinstein Eyal , Robert Leema , Rohrbach Marianne , Sanders Lynn , Sobey Glenda J. , Van Damme Tim , Vandersteen Anthony , van Mourik Caroline , Voermans Nicol , Wheeldon Nigel , Zschocke Johannes , Tinkle Brad
Published: March 2017

The Ehlers–Danlos syndromes (EDS) are a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Over the past two decades, the Villefranche Nosology, which delineated six subtypes, has been widely used as the standard for clinical diagnosis of EDS. For most of these subtypes, mutations had been identified in collagen‐encoding genes, or in genes encoding collagen‐modifying enzymes. Since its publication in 1998, a whole spectrum of novel EDS subtypes has been described, and mutations have been identified in an array of novel genes. The International EDS Consortium proposes a revised EDS classification, which recognizes 13 subtypes. For each of the subtypes, we propose a set of clinical criteria that are suggestive for the diagnosis. However, in view of the vast genetic heterogeneity and phenotypic variability of the EDS subtypes, and the clinical overlap between EDS subtypes, but also with other HCTDs, the definite diagnosis of all EDS subtypes, except for the hypermobile type, relies on molecular confirmation with identification of (a) causative genetic variant(s). We also revised the clinical criteria for hypermobile EDS in order to allow for a better distinction from other joint hypermobility disorders. To satisfy research needs, we also propose a pathogenetic scheme, that regroups EDS subtypes for which the causative proteins function within the same pathway. We hope that the revised International EDS Classification will serve as a new standard for the diagnosis of EDS and will provide a framework for future research purposes. © 2017 Wiley Periodicals, Inc.
Diagnosis, natural history, and management in vascular Ehlers–Danlos syndrome
Authors: Byers Peter H. , Belmont John , Black James , De Backer Julie , Frank Michael , Jeunemaitre Xavier , Johnson Diana , Pepin Melanie , Robert Leema , Sanders Lynn , Wheeldon Nigel
Published: March 2017

Vascular Ehlers Danlos syndrome (vEDS) is an uncommon genetic disorders characterized by arterial aneurysm, dissection and rupture, bowel rupture, and rupture of the gravid uterus. The frequency is estimated as 1/50,000–1/200,000 and results from pathogenic variants in COL3A1, which encodes the chains of type III procollagen, a major protein in vessel walls and hollow organs. Initial diagnosis depends on the recognitions of clinical features, including family history. Management is complex and requires multiple specialists who can respond to and manage the major complications. A summary of recommendations for management include: Identify causative variants in COL3A1 prior to application of diagnosis, modulate life style to minimize injury, risk of vessel/organ rupture, identify and create care team, provide individual plans for emergency care (“vascular EDS passport”) with diagnosis and management plan for use when traveling, centralize management at centers of excellence (experience) when feasible, maintain blood pressure in the normal range and treat hypertension aggressively, surveillance of vascular tree by doppler ultrasound, CTA (low radiation alternatives) or MRA if feasible on an annual basis. These recommendations represent a consensus of an international group of specialists with a broad aggregate experience in the care of individuals with vascular EDS that will need to be assessed on a regular basis as new information develops. © 2017 Wiley Periodicals, Inc.
Design, Synthesis, and Cytotoxic Evaluation of Certain 7‐Chloro‐4‐(piperazin‐1‐yl)quinoline Derivatives as VEGFR‐II Inhibitors
Authors: Aboul‐Enein Mohamed Nabil , El‐Azzouny Aida M. Abd El‐Sattar , Ragab Fatma Abdel‐Fattah , Hamissa Mohamed Farouk
Published: March 2017

Signaling pathway inhibition of VEGFR‐II is visualized as valuable tool in cancer management. In the current study, the synthesis of novel 1‐4‐(7‐chloroquinolin‐4‐yl)piperazin‐1‐yl)‐2‐(N‐substituted‐amino)‐ethanone derivatives (4a–t) was achieved through the amination of 2‐chloro‐1‐(4‐(7‐chloroquinolin‐4‐yl)piperazin‐1‐yl)ethanone (3) with different secondary amines. The structures of the target compounds were confirmed by IR, 1H‐NMR, 13C‐NMR, HRMS, and microanalysis. Compounds 4a–t were subjected to in vitro anticancer screening against human breast cancer (MCF‐7) and prostate cancer (PC3) cell lines. The highest cytotoxicty against both cell lines was displayed by 2‐(4‐(4‐bromobenzyl)piperazin‐1‐yl)‐1‐(4‐(7‐chloroquinolin‐4‐yl)piperazin‐1‐yl)ethanone (4q), with IC50 values of 6.502 and 11.751 μM against MCF‐7 and PC3 cells, respectively, compared with the standard drug doxorubicin (MCF‐7: 6.774 μM, PC3: 7.7316 μM). Due to its notable activity toward MCF‐7 cells, 4q was further evaluated as VEGFR‐II inhibitor, showing an IC50 of 1.38 μM compared to sorafenib (0.33 μM). The docking study proved that 4q has a binding mode akin to that of VEGFR‐II inhibitors.
Antiviral and Cytostatic Evaluation of 5‐(1‐Halo‐2‐sulfonylvinyl)‐ and 5‐(2‐Furyl)uracil Nucleosides
Authors: Wen Zhiwei , Suzol Sazzad H. , Peng Jufang , Liang Yong , Snoeck Robert , Andrei Graciela , Liekens Sandra , Wnuk Stanislaw F.
Published: March 2017

Transition metal‐catalyzed halosulfonylation of 5‐ethynyl uracil nucleosides provided (E)‐5‐(1‐chloro‐2‐tosylvinyl)uridines. Tetrabutylammonium fluoride‐mediated direct CH arylation of 5‐iodouracil nucleosides with furan or 2‐heptylfuran gave 5‐furyl‐substituted nucleosides without the necessity of using the organometallic substrates. These two classes of 5‐substituted uracil nucleosides as well their corresponding ester derivatives were tested against a broad range of DNA and RNA viruses and the human immunodeficiency virus (HIV). The 3′,5′‐di‐O‐acetyl‐5‐(E)‐(1‐chloro‐2‐tosylvinyl)‐2′‐deoxyuridine (24) inhibited the growth of L1210, CEM and HeLa cancer cells in the lower micromolar range. The (β‐chloro)vinyl sulfone 24 and 5‐(5‐heptylfur‐2‐yl)‐2′‐deoxyuridine (10) displayed micromolar activity against varicella zoster virus (VZV). The 5‐(5‐heptylfur‐2‐yl) analog 10 and its 3′,5′‐di‐O‐acetyl‐protected derivative showed similar activity against the cytomegalovirus (CMV). The 5‐(fur‐2‐yl) derivatives of 2′‐deoxyuridine and arabino‐uridine inhibited the replication of herpes simplex virus (HSV) TK+ strains while the 5‐(5‐heptylfur‐2‐yl) derivative 10 displayed antiviral activity against the parainfluenza virus.
Ejection of large particles from cometary nuclei in the shape of prolate ellipsoids
Authors: Gronkowski P. , Wesołowski M.
Published: March 2017

The ejection of cometary grains from comets is examined. It is assumed that cometary grains are chunks of ice‐dust material. We focus on cometary nuclei in the shape of prolate ellipsoids. Two mechanisms are considered. The first one is the drag acting on the motionless grains lying on the surface of a comet's nucleus. It is a consequence of the cometary ice's gentle sublimation. The second one is related to the cometary jet‐like phenomenon. This mechanism is associated with the rapid flow of gas streams into space from subsurface cavities in a comet's nucleus through narrow gaps and channels. The different elongations of ellipsoidal nuclei are examined. The formula for the maximum radius of grain that can be lifted up from the comet's nucleus is derived. The obtained algorithm takes into account the different cometo‐centric latitudes of places from which the cometary grains are ejected. We show that for a fixed mass of nucleus the maximum size of grains is an increasing function of nuclear flattening. Numerical simulation is carried out for a large range of assumed cometary parameters. The obtained results are in good agreement with the observations of the Comet 103P/Hartley carried out by the Deep Impact spacecraft.
Cerebrospinal fluid and plasma β‐endorphin levels in children with cerebral malaria
Authors: Olorunmoteni Oluwatosin Eunice , Adeodu Oluwagbemiga Oyewole , Oseni Saheed B. A. , Obuotor Efere M.
Published: March 2017

Objectives

Cerebral malaria (CM) is the most lethal form of malaria, yet its pathogenesis is not fully understood. Cytoadherence, sequestration, alterations in cytokine expression, inflammation, and microvascular obstruction are all hypothesized to be important in the aetio‐pathogenesis of coma which characterizes cerebral malaria and the death which sometimes result. Beta (β)‐endorphin has been postulated to be involved in the pathogenetic processes of inflammation and cytokine expression, although the exact role is unknown. The aim of this study was to determine the levels of β‐endorphin in cerebrospinal fluid (CSF) and plasma of children with CM and compare the levels of β‐endorphin in the plasma of children with CM with that of apparently healthy age‐ and sex‐matched controls at Ile‐Ife, Nigeria.

Materials and Methods

Additional to the standard investigation for CM, CSF and venous blood samples were obtained from the subjects for the determination of β‐endorphin levels.

Results

Forty children with CM were studied along with forty age‐ and sex‐matched controls. The mean CSF β‐endorphin (± SD) level for the children with CM was 1.8 ± 0.9 pmol/L. The mean plasma β‐endorphin levels at admission (3.1 ± 2.0 pmol/L) and discharge (4.1 ± 3.3 pmol/L) were higher in children with CM than in the control subjects (2.7 ± 0.7 pmol/L). However, only the mean plasma β‐endorphin levels at discharge was significantly higher than that of controls (p = .012).

Conclusion

Children with CM had higher mean plasma β‐endorphin levels compared to the controls and there was increased production of β‐endorphins in children with CM during the course of the illness.
Brain serotonin 4 receptor binding is inversely associated with verbal memory recall
Authors: Stenbæk Dea S. , Fisher Patrick M. , Ozenne Brice , Andersen Emil , Hjordt Liv V. , McMahon Brenda , Hasselbalch Steen G. , Frokjaer Vibe G. , Knudsen Gitte M.
Published: March 2017

Background

We have previously identified an inverse relationship between cerebral serotonin 4 receptor (5‐HT4R) binding and nonaffective episodic memory in healthy individuals. Here, we investigate in a novel sample if the association is related to affective components of memory, by examining the association between cerebral 5‐HT4R binding and affective verbal memory recall.

Methods

Twenty‐four healthy volunteers were scanned with the 5‐HT4R radioligand [11C]SB207145 and positron emission tomography, and were tested with the Verbal Affective Memory Test‐24. The association between 5‐HT4R binding and affective verbal memory was evaluated using a linear latent variable structural equation model.

Results

We observed a significant inverse association across all regions between 5‐HT4R binding and affective verbal memory performances for positive (p = 5.5 × 10−4) and neutral (p = .004) word recall, and an inverse but nonsignificant association for negative (p = .07) word recall. Differences in the associations with 5‐HT4R binding between word categories (i.e., positive, negative, and neutral) did not reach statistical significance.

Conclusion

Our findings replicate our previous observation of a negative association between 5‐HT4R binding and memory performance in an independent cohort and provide novel evidence linking 5‐HT4R binding, as a biomarker for synaptic 5‐HT levels, to the mnestic processing of positive and neutral word stimuli in healthy humans.