bluuebunny/crossref_metadata_2025 huggingface dataset:
NIH peer review percentile scores are poorly predictive of grant productivity
Authors: Fang Ferric C , Bowen Anthony , Casadevall Arturo
Published: February 2016

Peer review is widely used to assess grant applications so that the highest ranked applications can be funded. A number of studies have questioned the ability of peer review panels to predict the productivity of applications, but a recent analysis of grants funded by the National Institutes of Health (NIH) in the US found that the percentile scores awarded by peer review panels correlated with productivity as measured by citations of grant-supported publications. Here, based on a re-analysis of these data for the 102,740 funded grants with percentile scores of 20 or better, we report that these percentile scores are a poor discriminator of productivity. This underscores the limitations of peer review as a means of assessing grant applications in an era when typical success rates are often as low as about 10%.
Nitriding characteristics of 4H-SiC irradiated with remote nitrogen plasmas
Authors: Shimabayashi Masaharu , Kurihara Kazuaki , Horikawa Yoshimine , Sasaki Koichi
Published: February 2016

We examined the atomic concentrations and the weight densities of SiC surfaces irradiated with remote nitrogen plasmas. The unique approach of this work is that we compared the SiC surface irradiated with atomic nitrogen with that irradiated with a mixture of atomic nitrogen and molecular nitrogen in the metastable

state. As a result, it was found that molecular nitrogen in the

state has a higher efficiency than atomic nitrogen in the nitriding of SiC surfaces. The weight density measurements have revealed the removal of Si and C from the SiC surface by the irradiation of remote nitrogen plasma. These results suggest that the formation of volatile molecules is less significant when the SiC surface is irradiated with molecular nitrogen in the metastable

state.
A pan-cancer analysis of prognostic genes
Authors: Anaya Jordan , Reon Brian , Chen Wei-Min , Bekiranov Stefan , Dutta Anindya
Published: February 2016

Numerous studies have identified prognostic genes in individual cancers, but a thorough pan-cancer analysis has not been performed. In addition, previous studies have mostly used microarray data instead of RNA-SEQ, and have not published comprehensive lists of associations with survival. Using recently available RNA-SEQ and clinical data from The Cancer Genome Atlas for 6,495 patients, we have investigated every annotated and expressed gene’s association with survival across 16 cancer types. The most statistically significant harmful and protective genes were not shared across cancers, but were enriched in distinct gene sets which were shared across certain groups of cancers. These groups of cancers were independently recapitulated by both unsupervised clustering of Cox coefficients (a measure of association with survival) for individual genes, and for gene programs. This analysis has revealed unappreciated commonalities among cancers which may provide insights into cancer pathogenesis and rationales for co-opting treatments between cancers.
Initiating a watch list for Ebola virus antibody escape mutations
Authors: Miller Craig R. , Johnson Erin L. , Burke Aran Z. , Martin Kyle P. , Miura Tanya A. , Wichman Holly A. , Brown Celeste J. , Ytreberg F. Marty
Published: February 2016

The 2014 Ebola virus (EBOV) outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP) of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans) at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens.
Aeromagnetic investigation of southern Calabria and the Messina Straits (Italy): Tracking seismogenic sources of 1783 and 1908 earthquakes
Authors: Minelli Liliana , Vecchio Antonio , Speranza Fabio , Nicolosi Iacopo , D'Ajello Caracciolo Francesca , Chiappini Stefano , Carluccio Roberto , Chiappini Massimo
Published: February 2016

Southern Calabria and the NE corner of Sicily (Italy) were struck in 1783 and 1908 A.D. by two of the most catastrophic earthquakes ever in European history. Although it is generally acknowledged that the seisms were yielded by normal faults rupturing the upper crust of the Calabria‐Peloritani terrane, no consensus exists on seismogenic source location and orientation. Here we report on a high‐resolution low‐altitude aeromagnetic survey of southern Calabria and Messina Straits. In southern Calabria we document a broad weakly positive (5–10 nT) anomaly zone interrupted by three en echelon SW‐NE null to negative magnetic anomaly corridors. Euler deconvolution and magnetic modeling show that the anomaly pattern is produced by a 1–1.5 km thick crustal “layer” located within 3 km depth. This layer is offset by a 25 km long NE trending fault that corresponds to the Armo normal fault, recently inferred to be the source for the 1908 earthquake. Few kilometers to the south, we also document a subparallel and previously unrecognized fault, entering the Messina Straits and likely joining the Armo fault at depth. Further east, we model a 40 km long normal fault, probably extending northeastward for additional 40 km, running along the south Calabria axis from Aspromonte to the Serre mountains and partly following the 18 km long surface rupture witnessed by Déodat de Dolomieu after the 1783 earthquake. Thus, aeromagnetic data suggest that the sources of the 1783 and 1908 earthquakes are en echelon faults belonging to the same NW dipping normal fault system straddling the whole southern Calabria.
Effect of atmospheric refraction on radiative transfer in visible and near‐infrared band: Model development, validation, and applications
Authors: Hu Shuai , Gao Tai‐chang , Li Hao , Liu Lei , Liu Xi‐chuan , Zhang Ting , Cheng Tian‐ji , Li Wan‐tong , Dai Zhong‐hua , Su Xiaojian
Published: February 2016

Refraction is an important factor influencing radiative transfer since it can modify the propagation trajectory and polarization states of lights; therefore, it is necessary to quantitively evaluate the effect of atmospheric refraction on radiative transfer process. To this end, a new atmospheric radiative transfer model including refraction process is proposed. The model accuracy is validated against benchmark results, literature results, and well‐tested radiative transfer models such as discrete coordinate method and RT3/PolRadtran. The impact of atmospheric refraction on both polarized radiance and fluxes is discussed for pure Rayleigh scattering atmosphere, atmosphere with aerosol, and cloud. The results show that atmospheric refraction has a significant influence on both the radiance and polarization states of diffuse light, where the relative change of the radiance of reflected light and transmitted light due to refraction can achieve 6.3% and 7.4% for Rayleigh scattering atmosphere, 7.2% and 7.8% for atmosphere with aerosol, and 6.2% and 6.8% for cloudy atmosphere, respectively. The relative change of the degree of polarization ranges from near zero in the horizon to 9.5% near neutral points. The angular distribution pattern of the relative change of the radiance for atmosphere with aerosol and cloud is very similar to that for pure Rayleigh scattering case, where its magnitude decreases gradually with the increasing of zenith angle for reflected light; but for transmitted light, the variation characteristics is opposite. The impact of refraction is gradually enhanced with the increasing of solar zenith angles and the optical depth of aerosol and cloud. As the wavelength of incident light increases, the impact declines rapidly for Rayleigh scattering medium. The relative change of the fluxes due to refraction is most notable for Middle Latitude Winter profile (about 8.2043% and 7.3225% for the transmitted and reflected light, respectively, at 0.35 µm). With increasing the optical depth of aerosol, the influence of refraction on the fluxes is gradually enhanced. For cloudy atmosphere, the relative changes of the fluxes due to refraction are not very sensitive to the variation of cloud optical depth and effective radius of cloud drops.
Global volcanic aerosol properties derived from emissions, 1990–2014, using CESM1(WACCM)
Authors: Mills Michael J. , Schmidt Anja , Easter Richard , Solomon Susan , Kinnison Douglas E. , Ghan Steven J. , Neely Ryan R. , Marsh Daniel R. , Conley Andrew , Bardeen Charles G. , Gettelman Andrew
Published: February 2016

Accurate representation of global stratospheric aerosols from volcanic and nonvolcanic sulfur emissions is key to understanding the cooling effects and ozone losses that may be linked to volcanic activity. Attribution of climate variability to volcanic activity is of particular interest in relation to the post‐2000 slowing in the rate of global average temperature increases. We have compiled a database of volcanic SO2 emissions and plume altitudes for eruptions from 1990 to 2014 and developed a new prognostic capability for simulating stratospheric sulfate aerosols in the Community Earth System Model. We used these combined with other nonvolcanic emissions of sulfur sources to reconstruct global aerosol properties from 1990 to 2014. Our calculations show remarkable agreement with ground‐based lidar observations of stratospheric aerosol optical depth (SAOD) and with in situ measurements of stratospheric aerosol surface area density (SAD). These properties are key parameters in calculating the radiative and chemical effects of stratospheric aerosols. Our SAOD calculations represent a clear improvement over available satellite‐based analyses, which generally ignore aerosol extinction below 15 km, a region that can contain the vast majority of stratospheric aerosol extinction at middle and high latitudes. Our SAD calculations greatly improve on that provided for the Chemistry‐Climate Model Initiative, which misses about 60% of the SAD measured in situ on average during both volcanically active and volcanically quiescent periods.
Wetland tree transpiration modified by river‐floodplain connectivity
Authors: Allen Scott T. , Krauss Ken W. , Cochran J. Wesley , King Sammy L. , Keim Richard F.
Published: February 2016

Hydrologic connectivity provisions water and nutrient subsidies to floodplain wetlands and may be particularly important in floodplains with seasonal water deficits through its effects on soil moisture. In this study, we measured sapflow in 26 trees of two dominant floodplain forest species (Celtis laevigata and Quercus lyrata) at two hydrologically distinct sites in the lower White River floodplain in Arkansas, USA. Our objective was to investigate how connectivity‐driven water table variations affected water use, an indicator of tree function. Meteorological variables (photosynthetically active radiation and vapor pressure deficit) were the dominant controls over water use at both sites; however, water table variations explained some site differences. At the wetter site, highest sapflow rates were during a late‐season overbank flooding event, and no flood stress was apparent. At the drier site, sapflow decreased as the water table receded. The late‐season flood pulse that resulted in flooding at the wetter site did not affect the water table at the drier site; accordingly, higher water use was not observed at the drier site. The species generally associated with wetter conditions (Q. lyrata) was more positively responsive to the flood pulse. Flood water subsidy lengthened the effective growing season, demonstrating ecological implications of hydrologic connectivity for alleviating water deficits that otherwise reduce function in this humid floodplain wetland.
Are the oxygen isotopic compositions of Fitzroya cupressoides and Nothofagus pumilio cellulose promising proxies for climate reconstructions in northern Patagonia?
Authors: Lavergne Aliénor , Daux Valérie , Villalba Ricardo , Pierre Monique , Stievenard Michel , Vimeux Françoise , Srur Ana Marina
Published: February 2016

Tree ring δ18O chronologies from two native species (Fitzroya cupressoides and Nothofagus pumilio) in northern Patagonia were developed to assess their potential for paleoclimate reconstructions. The five annually resolved cellulose δ18O chronologies (two for F. cupressoides and three for N. pumilio) are located on the Andes along the steep west‐to‐east precipitation gradient. Over the common 60 years long interval, the five site‐δ18Ocell chronologies exhibit a strong common signal as indicated by the significant mean intercorrelation (r = 0.61, p < 0.05) and the high percentage (65%) of total variance explained by the first empirical orthogonal function. Although correlation analyses reveal that the two mean species‐δ18Ocell chronologies are mainly modulated by December–May temperature, the N. pumilio chronology shows a greater sensitivity to record temperature variations (r = 0.57, p < 0.05). The δ18Ocell of N. pumilio contains a regional temperature signal representative of a large area in southern South America under the influence of the Southern Annular Mode. This study indicates that δ18Ocell in N. pumilio is a promising proxy to reconstruct past variations in temperature in South America south of 38°S.
Using citizen science reports to define the equatorial extent of auroral visibility
Authors: Case N. A. , MacDonald E. A. , Viereck R.
Published: February 2016

An aurora may often be viewed hundreds of kilometers equatorward of the auroral oval owing to its altitude. As such, the NOAA Space Weather Prediction Center (SWPC) Aurora Forecast product provides a “view line” to demonstrate the equatorial extent of auroral visibility, assuming that it is sufficiently bright and high in altitude. The view line in the SWPC product is based upon the latitude of the brightest aurora, for each hemisphere, as specified by the real‐time oval variation, assessment, tracking, intensity, and online nowcasting (OVATION) Prime (2010) aurora precipitation model. In this study, we utilize nearly 500 citizen science auroral reports to compare with the view line provided by an updated SWPC aurora forecast product using auroral precipitation data from OVATION Prime (2013). The citizen science observations were recorded during March and April 2015 using the Aurorasaurus platform and cover one large geomagnetic storm and several smaller events. We find that this updated SWPC view line is conservative in its estimate and that the aurora is often viewable further equatorward than is indicated by the forecast. By using the citizen reports to modify the scaling parameters used to link the OVATION Prime (2013) model to the view line, we produce a new view line estimate that more accurately represents the equatorial extent of visible aurora. An OVATION Prime (2013) energy flux‐based equatorial boundary view line is also developed and is found to provide the best overall agreement with the citizen science reports, with an accuracy of 91%.
Threshold detection for the generalized Pareto distribution: Review of representative methods and application to the NOAA NCDC daily rainfall database
Authors: Langousis Andreas , Mamalakis Antonios , Puliga Michelangelo , Deidda Roberto
Published: February 2016

In extreme excess modeling, one fits a generalized Pareto (GP) distribution to rainfall excesses above a properly selected thresholdu. The latter is generally determined using various approaches, such as nonparametric methods that are intended to locate the changing point between extreme and nonextreme regions of the data, graphical methods where one studies the dependence of GP‐related metrics on the threshold levelu, and Goodness‐of‐Fit (GoF) metrics that, for a certain level of significance, locate the lowest thresholduthat a GP distribution model is applicable. Here we review representative methods for GP threshold detection, discuss fundamental differences in their theoretical bases, and apply them to 1714 overcentennial daily rainfall records from the NOAA‐NCDC database. We find that nonparametric methods are generally not reliable, while methods that are based on GP asymptotic properties lead to unrealistically high threshold and shape parameter estimates. The latter is justified by theoretical arguments, and it is especially the case in rainfall applications, where the shape parameter of the GP distribution is low; i.e., on the order of 0.1–0.2. Better performance is demonstrated by graphical methods and GoF metrics that rely on preasymptotic properties of the GP distribution. For daily rainfall, we find that GP threshold estimates range between 2 and 12 mm/d with a mean value of 6.5 mm/d, while the existence of quantization in the empirical records, as well as variations in their size, constitute the two most important factors that may significantly affect the accuracy of the obtained results.
Stochastic and anthropogenic influences on repeated record‐breaking temperature extremes in Australian spring of 2013 and 2014
Authors: Gallant Ailie J. E. , Lewis Sophie C.
Published: February 2016

We examine the contribution of synoptic and interannual processes and anthropogenic warming to repeated record‐breaking warmth in the Australian spring of 2013 and 2014. Climatic conditions similar to those in 2013 and 2014 have occurred in the past, the regional and large‐scale interannual processes associated with these extreme temperatures were not unusual, and the repetition of the very warm temperatures is likely to be a function of stochastic interannual variability. However, analysis using observations and climate model simulations shows that without an anthropogenically driven warming trend, it is unlikely that the 2013 and 2014 temperature anomalies would have been consecutively record breaking. Climate models demonstrate that the likelihood of consecutive record‐breaking spring temperatures similar to 2013 and 2014 changes from < 1% in simulations using natural forcing only to between 11% and 25% for the period 2006–2020 using simulations containing both natural and anthropogenic forcings.
Toward a re‐interpretation of self‐harm: A cross‐contextual approach
Authors: Latina Delia , Stattin Håkan
Published: February 2016

A common view is that self‐harmers are individuals who are exposed to or have been exposed to stressors and hostility in everyday settings. A strand of research has also found that self‐harmers expose other people to their hostility. Extending these findings, this study examined whether adolescent self‐harmers are simultaneously exposed and expose others to hostility in their everyday interpersonal contexts—at home, at school, and during leisure‐time. The participants were 1,482 adolescents, ranging from 13 to 16 years of age, who attended different schools in a medium‐sized city in central Sweden. The results show that the adolescents involved in mutually hostile relationships in their different interpersonal contexts exhibited higher self‐harm than the adolescents who were exposed to others’ hostility or exposed other people to their hostility. Also, the more mutually hostile settings the adolescents were involved in, the more self‐harm they reported. Overall, our findings suggest not only that self‐harmers are exposed to hostility in their different interpersonal contexts, as has been typically assumed, but also that they simultaneously expose others to hostility in these contexts. This has implications for our understanding of young people who harm themselves and also for intervention. Aggr. Behav. 42:522–532, 2016. © 2016 Wiley Periodicals, Inc.
Independent Association of Severity of Muscle Weakness With Disability as Measured by the Health Assessment Questionnaire Disability Index in Scleroderma
Authors: Paik Julie J. , Wigley Fredrick M. , Mejia Amanda F. , Hummers Laura K.
Published: February 2016

Objective

To determine whether the presence and degree of muscle weakness in scleroderma is associated with disability.

Methods

The study included a cohort of 1,718 scleroderma patients who had available data on muscle strength and disability. The primary independent variable was muscle weakness as defined by the maximum Medsger muscle severity score and the outcome was disability as measured by the last recorded Health Assessment Questionnaire disability index (HAQ DI) score. Univariate regression analyses were performed to assess the association of HAQ DI scores with the Medsger muscle severity score and other scleroderma characteristics. A multivariate regression analysis was performed to determine whether an association existed between the degree of muscle weakness and disability, while controlling for confounders.

Results

In 1,718 patients with scleroderma, 22.8% (392 of 1,718) had muscle weakness, as defined by a Medsger muscle severity score of ≥1. This subset was more likely than those without weakness to have diffuse cutaneous scleroderma (55.6% versus 35.1%; P < 0.0001), higher modified Rodnan skin thickness scores (mean ± SD 16.3 ± 13.7 versus 10.3 ± 10.6; P < 0.00001), shorter disease duration (mean ± SD 5.21 ± 6.75 versus 6.22 ± 7.67 years; P = 0.02), synovitis (17.7% versus 11.4%; P = 0.001), forced vital capacity <70% (46.2% versus 30.6%; P = 0.0001), and higher creatine kinase values (mean ± SD 441 ± 1,211 versus 151 ± 255; P = 0.00001). Both univariate and multivariate analyses revealed that for every unit of increase in the Medsger muscle severity score, there was a clinically significant (minimum clinically important difference ± 0.14) increase in the mean HAQ DI score at last followup visit.

Conclusion

The presence of muscle weakness associates with several features of worse disease burden and independently associates with disability as measured by the HAQ DI.
Adaptive tracking of sinusoids with unknown frequencies for some classes of SISO non‐minimum phase systems
Authors: Bartolini Giorgio , Estrada Antonio , Punta Elisabetta
Published: February 2016

In this paper, the output‐tracking problem for a class of non‐affine nonlinear systems with unstable zero‐dynamics is addressed. The system output must track a signal, which is the sum of a known number of sinusoids with unknown frequencies amplitudes and phases. The non‐minimum phase nature of the considered systems prevents the direct tracking by standard sliding mode methods, which are known to generate unstable behaviors of the internal dynamics. The proposed method relies on the properties of differentially flat systems under mild assumptions relevant to the relation between the original output and a suitably designed flat output. As a result, the original problem is transformed into a state‐tracking problem for invertible stable systems, where any internal state turns out to be bounded. Because of the uncertainty in the frequencies and in the parameters defining the relationship between system output and flat states, adaptive indirect methods are applied. Copyright © 2016 John Wiley & Sons, Ltd.
Injectable Stem Cell‐Laden Photocrosslinkable Microspheres Fabricated Using Microfluidics for Rapid Generation of Osteogenic Tissue Constructs
Authors: Zhao Xin , Liu Shen , Yildirimer Lara , Zhao Hong , Ding Ruihua , Wang Huanan , Cui Wenguo , Weitz David
Published: February 2016

Direct injection is a minimally invasive method of stem cell transplantation for numerous injuries and diseases. However, despite its promising potential, its clinical translation is difficult due to the low cell retention and engraftment after injection. With high versatility, high‐resolution control and injectability, microfabrication of stem‐cell laden biomedical hydrogels holds great potential as minimally invasive technology. Herein, a strategy of microfluidics‐assisted technology entrapping bone marrow‐derived mesenchymal stem cells (BMSCs) and growth factors in photocrosslinkable gelatin (GelMA) microspheres to ultimately generate injectable osteogenic tissue constructs is presented. Additionally, it is demonstrated that the GelMA microspheres can sustain stem cell viability, support cell spreading inside the microspheres and migration from the interior to the surface as well as enhance cell proliferation. This finding shows that encapsulated cells have the potential to directly and actively participate in the regeneration process. Furthermore, it is found that BMSCs encapsulated in GelMA microspheres show enhanced osteogenesis in vitro and in vivo, associated with a significant increase in mineralization. In short, the proposed strategy can be utilized to facilitate bone regeneration with minimum invasiveness, and can potentially be applied along with other matrices for extended applications.
Recent Developments in p‐Type Oxide Semiconductor Materials and Devices
Authors: Wang Zhenwei , Nayak Pradipta K. , Caraveo‐Frescas Jesus A. , Alshareef Husam N.
Published: February 2016

The development of transparent p‐type oxide semiconductors with good performance may be a true enabler for a variety of applications where transparency, power efficiency, and greater circuit complexity are needed. Such applications include transparent electronics, displays, sensors, photovoltaics, memristors, and electrochromics. Hence, here, recent developments in materials and devices based on p‐type oxide semiconductors are reviewed, including ternary Cu‐bearing oxides, binary copper oxides, tin monoxide, spinel oxides, and nickel oxides. The crystal and electronic structures of these materials are discussed, along with approaches to enhance valence‐band dispersion to reduce effective mass and increase mobility. Strategies to reduce interfacial defects, off‐state current, and material instability are suggested. Furthermore, it is shown that promising progress has been made in the performance of various types of devices based on p‐type oxides. Several innovative approaches exist to fabricate transparent complementary metal oxide semiconductor (CMOS) devices, including novel device fabrication schemes and utilization of surface chemistry effects, resulting in good inverter gains. However, despite recent developments, p‐type oxides still lag in performance behind their n‐type counterparts, which have entered volume production in the display market. Recent successes along with the hurdles that stand in the way of commercial success of p‐type oxide semiconductors are presented.
Prospects of Supercritical Fluids in Realizing Graphene‐Based Functional Materials
Authors: Padmajan Sasikala Suchithra , Poulin Philippe , Aymonier Cyril
Published: February 2016

Supercritical‐fluids science and technology predate all the approaches that are currently established for graphene production by several decades in advanced materials design. However, it has only recently been proposed as a plausible approach for graphene processing. Since then, supercritical fluids have emerged into contention as an alternative to existing technologies because of their scalability and versatility in processing graphene materials, which include composites, aerogels, and foams. Here, an overview is presented of such materials prepared through supercritical fluids from an advanced materials science standpoint, with a discussion on their fundamental properties and technological applications. The benefits of supercritical‐fluid processing over conventional liquid‐phase processing are presented. The benefits include not only better performances for advanced applications but also environmental issues associated with the synthesis process. Nevertheless, the limitations of supercritical‐fluid processing are also stressed, along with challenges that are still faced toward the achievement of the great expectations from graphene materials.
International Consensus Statement on Allergy and Rhinology: Rhinosinusitis Executive Summary
Authors: Orlandi Richard R. , Kingdom Todd T. , Hwang Peter H.
Published: February 2016

Background

The body of knowledge regarding rhinosinusitis (RS) continues to expand, with rapid growth in number of publications yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). This executive summary consolidates the findings of the ICAR:RS document.

Methods

ICAR:RS presents over 140 topics in the forms of evidence‐based reviews with recommendations (EBRRs) and evidence‐based reviews (EBR). The structured recommendations of the EBRR sections are summarized in this executive summary.

Results

This summary compiles the EBRRs regarding medical and surgical management of acute RS (ARS) and chronic RS with and without nasal polyps (CRSwNP and CRSsNP).

Conclusion

This ICAR:RS Executive Summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS.
Outcomes of revision endoscopic modified Lothrop procedure
Authors: Morrissey David K. , Bassiouni Ahmed , Psaltis Alkis J. , Naidoo Yuresh , Wormald Peter‐John
Published: February 2016

Background

Endoscopic modified Lothrop procedure (EMLP) is used to treat patients who fail conventional sinus surgery. The failure rate of a primary EMLP is reported to be between 5% and 32%. The failure rate of revision EMLP has not been reported. We present our institutions data regarding the outcome of patients requiring revision EMLP.

Methods

Data was collected prospectively. Patients undergoing primary EMLP between January 2001 and December 2013 with a minimum follow‐up of 6 months were included. Information related to demographics, asthma status, aspirin sensitivity, 22‐item Sino‐Nasal Outcome Test (SNOT‐22) score, Lund‐Mackay scores, intraoperative findings, and endoscopic ostium assessment were collected.

Results

There were 213 primary EMLPs completed with average follow‐up of 36 months. The failure rate of primary EMLP was 8.9% (19/213), whereas the failure rate of revision EMLP was 21% (4/19). Risk factors for failure of primary EMLP included the presence of intraoperative pus, more than 5 previous sinus operations and aspirin‐exacerbated respiratory disease (AERD). Revision of EMLP was undertaken primarily due to recurrence of nasal polyps or ostium stenosis. Those patients who underwent revision EMLP experienced symptomatic improvement and no major complications following the procedure.

Conclusion

The failure rate of revision EMLP is 21% in our series. The majority of revisions were for nasal polyp recurrence. Revision EMLP is a safe and well‐tolerated procedure in the small group of patients that require further surgery. Patients with intraoperative pus present at their initial EMLP, more than 5 previous sinus operations, or AERD are at increased risk of failure.
The endoscopic transseptal approach for choanal atresia repair
Authors: Wormald Peter‐John , Zhao Yi Chen , Valdes Constanza J. , Pacheco Alvaro E. , Ha Thanh Ngoc , Tewfik Marc A. , Wabnitz David , Shaw Chi‐kee Leslie
Published: February 2016

Background

There are many standard repair options for choanal atresia including puncture, dilatation and drilling of the atretic plate. Most of these techniques involve postoperative stenting, which may promote granulation and scarring, with possible progression to restenosis. This article describes a novel approach for choanal atresia repair without postoperative stenting.

Methods

This article describes our experience with this choanal atresia repair technique utilized in 16 pediatric patients and 1 adult patient across multiple tertiary pediatric and rhinology centers during 2008 through 2015. Seven cases were bilateral and 10 were unilateral. Surgery was performed using an endoscopic transseptal approach with preservation of the mucosa and creation of flaps. No stents or packing was used. The main outcome measures were: response to treatment based on endoscopic examination, need for further revision and incidence of complications.

Results

All patients underwent routine postoperative endoscopic inspection of their nasal cavity, postnasal space, and assessment of neochoanal patency. The neochoanae of all patients remained patent to a minimum follow‐up duration of 9 months with most patients follow up for 2 years or more. Two neonatal patients required transfusion postoperation from intraoperative bleeding. Two pediatric patients developed postoperative respiratory complications. One patient required revision surgery for nasal vestibule scarring from incision made on the nasal alar to facilitate the initial endoscopic approach.

Conclusion

This novel endoscopic transseptal repair technique is effective in the management of choanal atresia. Careful fashioning of mucosal flaps and the omission of stenting has resulted in lasting patency of the neochoanae.
Outcomes of chronic frontal sinusitis treated with ethmoidectomy: a prospective study
Authors: Abuzeid Waleed M. , Mace Jess C. , Costa Milena L. , Rudmik Luke , Soler Zachary M. , Kim Grace S. , Smith Timothy L. , Hwang Peter H.
Published: February 2016

Background

In medically refractory chronic frontal sinusitis, ethmoidectomy without instrumentation of the frontal ostium may resolve frontal disease. Our aim was to determine the efficacy of ethmoidectomy alone for the treatment of chronic frontal sinusitis.

Methods

Adults with chronic rhinosinusitis prospectively enrolled in a multicenter study who demonstrated frontal sinusitis on computed tomography were divided into 2 groups: (1) endoscopic sinus surgery (ESS) incorporating ethmoidectomy, but excluding frontal sinusotomy; and (2) ESS incorporating frontal sinusotomy. The primary outcome was improvement in 22‐item Sino‐Nasal Outcome Test (SNOT‐22) scores. Secondary outcomes included endoscopic scores and use of corticosteroids and antibiotics.

Results

A total of 196 cases undergoing frontal sinusotomy and 30 cases treated with ethmoidectomy without frontal sinusotomy were analyzed and were comparable demographically. The prevalence of nasal polyps, previous ESS, asthma, and aspirin intolerance was more common in the frontal sinusotomy group (p < 0.050). Preoperative endoscopy and computed tomography scores were higher in the frontal sinusotomy group (p ≤ 0.001). Postoperatively, both groups showed comparable SNOT‐22 scores with worse endoscopy scores in the frontal sinusotomy group (p = 0.038). Postoperative improvement in SNOT‐22 total and subdomain scores was comparable between groups. Nasal endoscopy scores improved to a greater degree in the frontal sinusotomy group (p = 0.023). Duration of postoperative topical steroid use was higher in the frontal sinusotomy group (p = 0.007). Revision surgery was needed in 2.6% of frontal sinusotomy patients and 0% of patients without frontal sinusotomy.

Conclusion

The treatment of chronic frontal sinusitis through ethmoidectomy is a potential alternative to frontal sinusotomy achieving similar quality of life (QOL) improvements in patients manifesting less severe sinus disease.
Conformational Studies and Atropisomerism Kinetics of the ALK Clinical Candidate Lorlatinib (PF‐06463922) and Desmethyl Congeners
Authors: Elleraas Jeff , Ewanicki Jason , Johnson Ted W. , Sach Neal W. , Collins Michael R. , Richardson Paul F.
Published: February 2016

Lorlatinib (PF‐06463922) is an ALK/ROS1 inhibitor and is in clinical trials for the treatment of ALK positive or ROS1 positive NSCLC (i.e. specific subsets of NSCLC). One of the laboratory objectives for this molecule indicated that it would be desirable to advance a molecule which was CNS penetrant in order to treat brain metastases. From this perspective, a macrocyclic template was attractive for a number of reasons. In particular, this template reduces the number of rotatable bonds, provides the potential to shield polar surface area and reinforces binding through a restricted conformation. All of these features led to better permeability for the molecules of interest and thus increased the chance for better blood brain barrier penetration. With a CNS penetrant molecule, kinase selectivity is a key consideration particularly with regard to proteins such as TrkB, which are believed to influence cognitive function. Removal of the chiral benzylic methyl substituent from lorlatinib was perceived as not only a means to simplify synthetic complexity, but also as a strategy to further truncate the molecule of interest. Examination of the NMR of the desmethyl analogues revealed that the compound existed as a mixture of atropisomers, which proved separable by chiral SFC. The individual atropisomers were evaluated through a series of in vitro assays, and shown to have a favorable selectivity profile when compared to lorlatinib. The challenge to develop such a molecule lies in the rate at which the atropisomers interchange dictated by the energy barrier required to do this. Here, we describe the synthesis of the desmethyl macrocycles, conformational studies on the atropisomers, and the kinetics of the interconversion. In addition, the corresponding conformational studies on lorlatinib are reported providing a hypothesis for why a single diastereomer is observed when the chiral benzylic methyl group is introduced.
Superspreading on Immersed Gel Surfaces for the Confined Synthesis of Thin Polymer Films
Authors: Zhang Pengchao , Zhang Feilong , Zhao Chuangqi , Wang Shutao , Liu Mingjie , Jiang Lei
Published: February 2016

Liquid spreading is of significant interest in science and technology. Although surface topography engineering and liquid surface‐tension regulating can facilitate spreading, the spreading layers in these strategies are inevitably inhomogeneous or contaminated with surfactants. Herein, we show a general strategy to realize the superspreading of liquids on mutually soluble gel surfaces. The cooperation of the hydraulic pressure under liquid phase and liquid‐like property of gel surfaces can dramatically eliminate the local pinning effect and enhance the advancement of three‐phase contact line, thus forming stable and homogeneous superspreading liquid layers. Such liquid layers can be converted into various functional thin polymer films with controlled thicknesses (nm‐ to µm‐scale) through one‐step polymerization of the reactants. Our strategy offers opportunities for large‐scale synthesis of versatile functional thin films for various applications.
Intramolecular Cyclopropanation of 1,4‐Dienes through Hydroboration–Homologation: Easy Access to Bicyclo[3.1.0]hexanes
Authors: Xu Gong , Renaud Philippe
Published: February 2016

An intramolecular cyclopropanation reaction involving B‐(1‐chloroalkyl)catecholborane intermediates generated from 1,4‐dienes through hydroboration with catecholborane and Matteson homologation was developed. This sequential procedure leading to bicyclo[3.1.0]hexanes involves the formation of three new sigma C−C bonds at the same carbon atom. A mechanistic study supports the involvement of carbocationic intermediates.
Tailored Cyclic and Linear Polycarbosilazanes by Barium‐Catalyzed N−H/H−Si Dehydrocoupling Reactions
Authors: Bellini Clément , Orione Clément , Carpentier Jean‐François , Sarazin Yann
Published: February 2016

Ba[CH(SiMe3)2]2(THF)3catalyzes the fast and controlled dehydrogenative polymerization of Ph2SiH2andp‐xylylenediamine to afford polycarbosilazanes. The structure (cyclic versus linear; end‐groups) and molecular weight of the macromolecules can be tuned by adjusting the Ph2SiH2/diamine feed ratio. A detailed analysis of the resulting materials (mol. wt up to ca. 10 000 g mol−1) is provided.
Spectroscopic Characterization and Reactivity of Triplet and Quintet Iron(IV) Oxo Complexes in the Gas Phase
Authors: Andris Erik , Jašík Juraj , Gómez Laura , Costas Miquel , Roithová Jana
Published: February 2016

Closely structurally related triplet and quintet iron(IV) oxo complexes with a tetradentate aminopyridine ligand were generated in the gas phase, spectroscopically characterized, and their reactivities in hydrogen‐transfer and oxygen‐transfer reactions were compared. The spin states were unambiguously assigned based on helium tagging infrared photodissociation (IRPD) spectra of the mass‐selected iron complexes. It is shown that the stretching vibrations of the nitrate counterion can be used as a spectral marker of the central iron spin state.
FeOOH/Co/FeOOH Hybrid Nanotube Arrays as High‐Performance Electrocatalysts for the Oxygen Evolution Reaction
Authors: Feng Jin‐Xian , Xu Han , Dong Yu‐Tao , Ye Sheng‐Hua , Tong Ye‐Xiang , Li Gao‐Ren
Published: February 2016

Herein, we developed FeOOH/Co/FeOOH hybrid nanotube arrays (HNTAs) supported on Ni foams for oxygen evolution reaction (OER). The inner Co metal cores serve as highly conductive layers to provide reliable electronic transmission, and can overcome the poor electrical conductivity of FeOOH efficiently. DFT calculations demonstrate the strong electronic interactions between Co and FeOOH in the FeOOH/Co/FeOOH HNTAs, and the hybrid structure can lower the energy barriers of intermediates and thus promote the catalytic reactions. The FeOOH/Co/FeOOH HNTAs exhibit high electrocatalytic performance for OER, such as low onset potential, small Tafel slope, and excellent long‐term durability, and they are promising electrocatalysts for OER in alkaline solution.
Enantioselective Rhodium‐Catalyzed Dearomative Arylation or Alkenylation of Quinolinium Salts
Authors: Wang Yan , Liu Yunlong , Zhang Dongdong , Wei Hao , Shi Min , Wang Feijun
Published: February 2016

A highly enantioselective rhodium(I)‐catalyzed dearomative arylation or alkenylation of easily available N‐alkylquinolinium salts is reported, thus providing an effective and practical approach to the synthesis of dihydroquinolines in up to 99 % ee. This reaction tolerates a wide range of functional groups with respect to both the organic boronic acids and the quinoline starting materials. Moreover, the synthetic utility of this protocol is demonstrated in the formal asymmetric synthesis of bioactive tetrahydroquinoline and the total syntheses of (−)‐angustureine and (+)‐cuspareine.
PLA/functionalized‐gum arabic based bionanocomposite films for high gas barrier applications
Authors: Tripathi Neelima , Katiyar Vimal
Published: February 2016

The present work focuses on the microwave synthesis of lactic acid‐grafted‐gum arabic (LA‐g‐GA) by polycondensation reaction and its influence as an additive to improve the gas barrier properties of poly(lactic acid) (PLA) films, prepared by solution casting method. It is observed that during the synthesis of LA‐g‐GA, hydrophilic gum is converted into hydrophobic due to grafting of in situ grown hydrophobic oligo‐(lactic acid). Subsequently, PLA/LA‐g‐GA bionanocomposite films are fabricated and characterized for structural, thermal, mechanical and gas barrier properties. Path breaking reduction in oxygen permeability (OP) of ∼10 folds is achieved in case of PLA films containing LA‐g‐GA as filler. However, water vapor transmission rate (WVTR) is reduced up to 27% after 5 wt % addition of filler. Reduction in OP of this order of magnitude enables the PLA to compete with PET in term of enhancing shelf life and maintaining the food quality. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43458.
Increased DNA Methylation and Reduced Expression of Transcription Factors in Human Osteoarthritis Cartilage
Authors: Alvarez‐Garcia Oscar , Fisch Kathleen M. , Wineinger Nathan E. , Akagi Ryuichiro , Saito Masahiko , Sasho Takahisa , Su Andrew I. , Lotz Martin K.
Published: February 2016

Objective

To analyze the methylome of normal and osteoarthritic (OA) knee articular cartilage and to determine the role of DNA methylation in the regulation of gene expression in vitro.

Methods

DNA was isolated from human normal (n = 11) and OA (n = 12) knee articular cartilage and analyzed using the Infinium HumanMethylation450 BeadChip array. To integrate methylation and transcription, RNA sequencing was performed on normal and OA cartilage and validated by quantitative polymerase chain reaction. Functional validation was performed in the human TC28 cell line and primary chondrocytes that were treated with the DNA methylation inhibitor 5‐aza‐2′‐deoxycytidine (5‐aza‐dC).

Results

DNA methylation profiling revealed 929 differentially methylated sites between normal and OA cartilage, comprising a total of 500 individual genes. Among these, 45 transcription factors that harbored differentially methylated sites were identified. Integrative analysis and subsequent validation showed a subset of 6 transcription factors that were significantly hypermethylated and down‐regulated in OA cartilage (ATOH8, MAFF, NCOR2, TBX4, ZBTB16, and ZHX2). Upon 5‐aza‐dC treatment, TC28 cells showed a significant increase in gene expression for all 6 transcription factors. In primary chondrocytes, ATOH8 and TBX4 were increased after 5‐aza‐dC treatment.

Conclusion

Our findings reveal that normal and OA knee articular cartilage have significantly different methylomes. The identification of a subset of epigenetically regulated transcription factors with reduced expression in OA may represent an important mechanism to explain changes in the chondrocyte transcriptome and function during OA pathogenesis.
Brief Report: Arthritis in KRN T Cell Receptor–Transgenic Mice Does Not Require Interleukin‐17 or Th17 Cells
Authors: Auger Jennifer L. , Cowan Hannah M. , Engelson Brianna J. , Kashem Sakeen W. , Prinz Immo , Binstadt Bryce A.
Published: February 2016

Objective

Th17 cells and interleukin‐17 (IL‐17) cytokine family members are implicated in the pathogenesis of many rheumatic diseases. Most studies in mouse models of inflammatory arthritis have demonstrated a key role for the proinflammatory cytokine IL‐17A and its receptor, the IL‐17 receptor (IL‐17R) A/C heterodimer. The aim of this study was to use a rigorous genetic approach to evaluate the contribution of Th17 cells and IL‐17 in the autoantibody‐dependent KRN T cell receptor–transgenic mouse model of arthritis.

Methods

We bred KRN mice expressing the major histocompatibility complex class II molecule Ag7 (referred to as K/B/g7 mice) and genetically lacking the related cytokines IL‐17A and IL‐17F or their critical receptor subunit, IL‐17RA. Using bone marrow transplantation, we generated mice in which hematopoietic cells from K/B/g7 donor mice lacked the key Th17‐differentiating transcription factor, retinoic acid receptor–related orphan nuclear receptor γt (Rorγt).

Results

K/B/g7 mice lacking both IL‐17A and IL‐17F produced normal titers of pathogenic autoantibodies, and arthritis developed in a typical manner. Similarly, neither IL‐17RA nor Rorγt expression by hematopoietic cells was required for disease development in this model.

Conclusion

Despite prior reports suggesting that Th17 cells and IL‐17A are crucially involved in the pathogenesis of arthritis in K/BxN mice, the results presented here provide genetic evidence that IL‐17A and IL‐17F, IL‐17RA, and Rorγt expression by hematopoietic cells are dispensable for normal arthritis progression in the K/B/g7 mouse model system. We discuss potential explanations for the discrepancies between these 2 highly similar model systems. These findings plus those in other mouse models of arthritis provide insight regarding why therapeutic biologic agents targeting the Th17/IL‐17 axis are beneficial in some human rheumatic diseases but not others.