bluuebunny/crossref_metadata_2025 huggingface dataset:
Variable remanence acquisition efficiency in sediments containing biogenic and detrital magnetites: Implications for relative paleointensity signal recording
Authors: Ouyang Tingping , Heslop David , Roberts Andrew P. , Tian Chengjing , Zhu Zhaoyu , Qiu Yan , Peng Xuechao
Published: June 2014

Widespread geological preservation of biogenic magnetite makes it important to assess how such particles contribute to sedimentary paleomagnetic signals. We studied a sediment core from the South China Sea that passes the strict empirical criteria for magnetic “uniformity” used in relative paleointensity studies. Such assessments are based routinely on bulk magnetic parameters that often fail to enable identification of mixed magnetic mineral assemblages. Using techniques that enable component‐specific magnetic mineral identification, we find that biogenic and detrital magnetites occur in approximately equal concentrations within the studied sediments. We analyzed normalized remanence signals associated with the two magnetite components to assess whether co‐occurring biogenic and detrital magnetites record geomagnetic information in the same way and with the same efficiency. Paleomagnetic directions for the two components have no phase lag, which suggests that the biogenic and detrital magnetites acquired their magnetizations at equivalent times. However, we find that the biogenic magnetite is generally 2–4 times more efficient as the detrital magnetite in contributing to the natural remanent magnetization (NRM) despite their approximately equal magnetic contributions. Variations in the concentration and efficiency of remanence acquisition of the two components suggest that a significant part of the NRM is controlled by nongeomagnetic factors that will affect relative paleointensity recording. We recommend that methods suited to the detection of variable recording efficiency associated with biogenic and detrital magnetites should be used on a routine basis in relative paleointensity studies.
Skeletal oxygen and carbon isotope compositions of Acropora coral primary polyps experimentally cultured at different temperatures
Authors: Nishida Kozue , Ishikawa Kei , Iguchi Akira , Tanaka Yasuaki , Sato Mizuho , Ishimura Toyoho , Inoue Mayuri , Nakamura Takashi , Sakai Kazuhiko , Suzuki Atsushi
Published: June 2014

We investigated temperature and growth‐rate dependency of skeletal oxygen and carbon isotopes in primary polyps of Acropora digitifera (Scleractinia: Acroporidae) by culturing them at 20, 23, 27, or 31°C. Calcification was most rapid at 27 and 31°C. We obtained a δ18O‐temperature relationship (−0.18‰ °C−1) consistent with reported ranges for Porites, indicating that juvenile Acropora polyps can be used for temperature reconstruction. A growth‐rate dependency of skeletal isotopes was detected in the experimental polyps cultured at lower water temperatures, when the skeletal growth rate of these polyps was also low. The estimated upper calcification flux limit for a kinetic isotope effect to be observed in the δ18O‐growth rate relationship (∼0.4–0.7 g CaCO3 cm−2 yr−1) was similar to the calcification flux in Porites corresponding to a linear extension rate of 5 mm yr−1, the maximum rate at which the kinetic isotope effect is evident. This result suggests that the calcification flux can be used as a measure of growth rate‐related isotope fractionation, that is, the kinetic isotope effect, in corals of different genera and at different growth stages.
Pb isotope compositions of detrital K‐feldspar grains in the upper‐middle Yangtze River system: Implications for sediment provenance and drainage evolution
Authors: Zhang Zengjie , Tyrrell Shane , Li Chang'an , Daly J. Stephen , Sun Xilin , Li Qiwen
Published: June 2014

The upper‐middle Yangtze River drains the Qiangtang Block, the Songpan‐Ganzi, the Yangtze Craton, and the Qinling‐Dabie orogenic belt. These tectonic units have been shown to have heterogeneous Pb isotopic compositions, which allow this isotope system to be used as a sediment provenance tool. In this study we have employed laser ablation multiple collector inductively coupled plasma mass spectrometry (LA‐MC‐ICPMS) to measure Pb isotope compositions of sand‐sized K‐feldspar grains from the upper‐middle Yangtze River. Data are presented from four major tributaries: Yalongjiang, Minjiang, Jialingjiang, and Hanjiang, as well as from the main Yangtze River near Yichang. A portion of K‐feldspar grains in the Yalongjiang shows an ultraradiogenic character (206Pb/204Pb > 20), which is unique in the upper‐middle Yangtze. Moreover, these ultraradiogenic grains were transported as far as Yichang, just downstream from the Three Gorges, suggesting that the Pb‐in‐K‐feldspar method could be applied to the sediments within the Jianghan Basin to date the formation of the Three Gorges. Pb isotopic data from Yichang indicate that erosion in the Longmen Shan and neighboring regions is more important than the Jinshajiang in supplying sediment. The grains in Hanoi Basin have little overlap with the Songpan‐Ganzi, but show a good match with the Yangtze Craton in its range of lower 206Pb/204Pb ratios. These observations support the idea that the “Middle Yangtze” used to be a tributary of the paleo‐Red River and that there has been no drainage linking the Songpan‐Ganzi and the Red River since the Eocene.
Urban impacts on mean and trend of surface incident solar radiation
Authors: Wang Kaicun , Ma Qian , Wang XiaoYan , Wild Martin
Published: June 2014

Anthropogenic aerosols over urban areas may have important effects on surface incident solar radiation (Rs). Studies have claimed that Rs decreased significantly more in urban areas than in rural areas from 1964 to 1989. However, these estimates have substantial biases because they ignored the spatial inhomogeneity of Rs measurements. To address this issue, we selected urban‐rural station pairs collocated within 2° × 2° and found 105 such pairs based on the Global Energy Balance Archive (GEBA). On average, the impact of urban aerosols on mean and trend of Rs is 0.2(0.7, median) ± 11.2 W m−2 and 0.1(−0.7, median) ± 6.6 W m−2 per decade from 1961 to 1990, respectively. Hence, the averaged urban impacts on the mean and trend of Rs over Europe, China and Japan from 1961 to 1990 are small although they may be significant at specific sites.
Experimental evidence for the formation of liquid saline water on Mars
Authors: Fischer Erik , Martínez Germán M. , Elliott Harvey M. , Rennó Nilton O.
Published: June 2014

Evidence for deliquescence of perchlorate salts has been discovered in the Martian polar region while possible brine flows have been observed in the equatorial region. This appears to contradict the idea that bulk deliquescence is too slow to occur during the short periods of the Martian diurnal cycle during which conditions are favorable for it. We conduct laboratory experiments to study the formation of liquid brines at Mars environmental conditions. We find that when water vapor is the only source of water, bulk deliquescence of perchlorates is not rapid enough to occur during the short periods of the day during which the temperature is above the salts' eutectic value, and the humidity is above the salts' deliquescence value. However, when the salts are in contact with water ice, liquid brine forms in minutes, indicating that aqueous solutions could form temporarily where salts and ice coexist on the Martian surface and in the shallow subsurface.
Seasonal differences in the sunrise undulations at the dip equator at solar minimum at two distinct locations and their relation with postsunset electrodynamics
Authors: Ambili K. M. , Choudhary R. K. , St.‐Maurice J.‐P.
Published: June 2014

A sunrise undulation (SU) is observed by ionosondes when new ionization is produced at sunrise in the upper F region at the geomagnetic equator. It creates a very quick upward transition in the F region peak altitude (hmF2), which subsequently undergoes a sharp descent at a rate far in excess of any electrodynamic drift. The peak density also increases rapidly during the descent. However, the detection of the new plasma with ionosondes is possible only if plasma from the night before has undergone enough recombination, which, on average, can vary from one location to another and one season to the next. With this in mind, we have studied seasonal variations in the SU occurrence in 2010 at two widely separated geomagnetic equatorial stations in longitude, at Jicamarca in Peru and Trivandrum in India. Noticeable differences were found in the characteristics of undulation observed at the two locations. While full undulation (both ascend and descend in hmF2) was observed throughout the year at Trivandrum, only the descending part of undulation was visible at Jicamarca. Plasma density just before sunrise, on average, was 2 times larger at Jicamarca than at Trivandrum. The average hmF2, which peaks during night, was also higher at Jicamarca by as much as 100 km compared to Trivandrum. We traced the origin of these differences to the evolution of zonal electric field between sunset and local midnight at the two locations. The downward drift during this period was steeper at Trivandrum compared to Jicamarca, particularly during equinox. In addition, the strength of the downward drifts at Jicamarca decreased and even underwent a sign reversal prior to sunrise during equinox and winter months. In comparison, the downward motion at Trivandrum only became stronger during early morning hours. The contrast between the vertical drift at the two stations provides a very reasonable qualitative explanation for the differences in the characteristics of SU observed at the two stations.
Analytical model for flow duration curves in seasonally dry climates
Authors: Müller Marc F. , Dralle David N. , Thompson Sally E.
Published: June 2014

Flow duration curves (FDC) display streamflow values against their relative exceedance time. They provide critical information for watershed management by representing the variation in the availability and reliability of surface water to supply ecosystem services and satisfy anthropogenic needs. FDCs are particularly revealing in seasonally dry climates, where surface water supplies are highly variable. While useful, the empirical computation of FDCs is data intensive and challenging in sparsely gauged regions, meaning that there is a need for robust, predictive models to evaluate FDCs with simple parameterization. Here, we derive a process‐based analytical expression for FDCs in seasonally dry climates. During the wet season, streamflow is modeled as a stochastic variable driven by rainfall, following the stochastic analytical model of Botter et al. (2007a). During the dry season, streamflow is modeled as a deterministic recession with a stochastic initial condition that accounts for the carryover of catchment storage across seasons. The resulting FDC model is applied to 38 catchments in Nepal, coastal California, and Western Australia, where FDCs are successfully modeled using five physically meaningful parameters with minimal calibration. A Monte Carlo analysis revealed that the model is robust to deviations from its assumptions of Poissonian rainfall, exponentially distributed response times and constant seasonal timing. The approach successfully models period‐of‐record FDCs and allows interannual and intra‐annual sources of variations in dry season streamflow to be separated. The resulting median annual FDCs and confidence intervals allow the simulation of the consequences of interannual flow variations for infrastructure projects. We present an example using run‐of‐river hydropower in Nepal as a case study.
Spatiotemporal flood sensitivity to annual precipitation: Evidence for landscape‐climate coevolution
Authors: Perdigão Rui A. P. , Blöschl Günter
Published: June 2014

This study investigates the sensitivity of floods to annual precipitation in space and time and evaluates quantitative signs of landscape‐climate coevolution. For that purpose, a spatiotemporal sensitivity analysis is performed at regional scale using data from 804 catchments in Austria from 1976 to 2008. Results show that flood peaks are more responsive to spatial (regional) than to temporal (decadal) variability. Space‐wise a 10% increase in precipitation leads to a 23% increase in flood peaks in Austria, whereas time‐wise a 10% increase in precipitation leads to an increase of just 6% in flood peaks. Catchments from dry lowlands and high wetlands exhibit similarity between the spatial and temporal sensitivities (spatiotemporal symmetry) and low landscape‐climate codependence. This suggests that such regions are not coevolving significantly. However, intermediate regions show differences between those sensitivities (symmetry breaks) and higher landscape‐climate codependence, suggesting undergoing coevolution. A new coevolution index is then proposed relating spatiotemporal symmetry with relative characteristic celerities. The descriptive assessment of coevolution is complemented by a simple dynamical model of landscape‐climate coevolution, in which landform evolution processes take place at the millennial scale (slow dynamics), and climate adjusts in years to decades (fast dynamics). Coevolution is expressed by the interplay between slow and fast dynamics, represented, respectively, by spatial and temporal characteristics. The model captures key features of the joint landscape‐climate distribution, supporting the descriptive assessment. This paper ultimately brings to light that coevolution needs to be taken into account through characteristic celerities in space‐time trading of regional hydrology.
Use of Oral and Subcutaneous Methotrexate in Rheumatoid Arthritis Patients in the United States
Authors: Curtis Jeffrey R. , Zhang Jie , Xie Fenglong , Beukelman Tim , Chen Lang , Fernandes Joaquim , Ginsberg Seth , Spettell Claire , Yun Huifeng , Saag Kenneth G. , Schiff Michael
Published: June 2014

Objective

To examine the patterns of methotrexate (MTX) use among rheumatoid arthritis (RA) patients.

Methods

Using data from RA patients enrolled in a US commercial health plan and the US Medicare program, we identified RA patients initiating oral MTX. Persistence with MTX (oral or subcutaneous [SC]) was defined as no gap for ≥90 days.

Results

New oral MTX users in Medicare (n = 20,431) were 76.9% women, had a mean ± SD age of 69.7 ± 11.7 years, and contributed a median followup of 2.6 years (interquartile range 1.7–3.5 years). Only 38% received dosages ≥20 mg/week at any time. Approximately 50% of patients discontinued MTX at 1 year, although more than one‐third of patients subsequently restarted. New commercially insured oral MTX users (n = 4,048) were similar to Medicare patients, except for age. Among Medicare patients, 19% starting oral MTX subsequently initiated a biologic agent, mostly anti–tumor necrosis factor (85%). Of these, only 50% received MTX at a dosage of ≥20 mg/week, and only 21% of individuals switched to SC MTX (4%) or received hydroxychloroquine (8%), sulfasalazine (5%), or leflunomide (8%) prior to biologic agents. In commercially insured patients, 35% initiated a biologic agent, mostly anti–tumor necrosis factor therapies (90%). Of these, 43% never received MTX ≥20 mg/week.

Conclusion

Titration to a higher‐dose oral MTX and use of SC MTX among RA patients were infrequent and may have been underutilized. Further work to optimize MTX dosing before patients are switched to a biologic agent may be warranted.
Subcutaneous Tocilizumab Versus Placebo in Combination With Disease‐Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis
Authors: Kivitz Alan , Olech Ewa , Borofsky Michael , Zazueta Beatriz M. , Navarro‐Sarabia Federico , Radominski Sebastião C. , Merrill Joan T. , Rowell Lucy , Nasmyth‐Miller Clare , Bao Min , Wright Stephen , Pope Janet E.
Published: June 2014

Objective

The efficacy and safety of subcutaneous tocilizumab (TCZ‐SC) versus subcutaneous placebo (PBO‐SC) was evaluated in patients with rheumatoid arthritis who had an inadequate response to disease‐modifying antirheumatic drugs in the BREVACTA study.

Methods

Patients (n = 656) were randomized 2:1 to receive TCZ‐SC 162 mg every other week or PBO‐SC every other week for 24 weeks; 20% previously received anti–tumor necrosis factor treatment. Escape therapy with TCZ‐SC 162 mg weekly was offered from week 12 for inadequate response. The primary end point was the American College of Rheumatology 20% improvement (ACR20) response at week 24. The key secondary outcomes were radiographic progression and safety.

Results

TCZ‐SC was superior to PBO‐SC for ACR20 response at week 24 (60.9% versus 31.5%; P < 0.0001). All secondary end points showed TCZ‐SC to be superior to PBO‐SC, including ACR50 and ACR70 response (40% and 20% for TCZ‐SC, respectively, and 12% and 5% for PBO‐SC, respectively; P < 0.0001 for both) and Disease Activity Score in 28 joints (DAS28) remission (DAS28 <2.6; 32% versus 4% [P < 0.0001]). The mean change in modified Sharp/van der Heijde score was significantly lower in the TCZ‐SC group than the PBO‐SC group (0.62 versus 1.23; P = 0.0149). Adverse events (AEs) and serious AEs (SAEs) were comparable between the TCZ‐SC and PBO‐SC groups; 4.6% and 3.7% of patients had at least 1 SAE, respectively, and infection was the most common SAE in 2.1% and 1.8% of patients, respectively. More injection site reactions occurred with TCZ‐SC than PBO‐SC (7.1% versus 4.1%). No anaphylaxis or serious hypersensitivity reactions occurred. There were 3 deaths in the TCZ‐SC group and 0 in the PBO‐SC group.

Conclusion

TCZ‐SC every other week had significantly greater efficacy, including ACR end points and inhibition of joint damage, compared with PBO‐SC. TCZ‐SC was well tolerated and its safety profile was comparable with that of previous intravenous TCZ studies.
Trilevel‐Structured Superhydrophobic Pillar Arrays with Tunable Optical Functions
Authors: Wooh Sanghyuk , Koh Jai Hyun , Lee Soojin , Yoon Hyunsik , Char Kookheon
Published: June 2014

Water‐repelling surfaces inspired by lotus leaves have been developed for their commercial needs in superhydrophobic and self‐cleaning coatings on glasses and windows. The extraordinary properties originate from their multiscale structures with waxy materials. To obtain high transparency as well as superhydrophobicity, microhair arrays are designed with large spacing to reduce optical scattering effects caused by microstructures, but with a trilevel hierarchical structure to compensate for the loss of superhydrophobicity. In this study, a soft molding technique on wet pastes consisting of nanoparticles (NPs) is proposed to create a multilevel hierarchical structure of sub‐100 nm nanoparticles, which demonstrates excellent water repellency. Additionally, full advantage is taken of the TiO2 NP mesoporous structure for UV protection and for its ability to attach to various kinds of functional (for example, photoresponsive) dyes. Furthermore, the stability of fluorinated surfaces against UV light is enhanced by the passivation of the TiO2 surface with a thin silica coating.
The Habsburg Jaw—Re‐examined
Authors: Peacock Zachary S. , Klein Katherine P. , Mulliken John B. , Kaban Leonard B.
Published: June 2014

“Habsburg Jaw” is a frequently used eponymous designation for patients with mandibular prognathism, hyperplasia, or overgrowth. The purpose of this study was to evaluate portraits of the Spanish Habsburgs to determine the relative contributions of maxillary deficiency and mandibular prognathism to overall facial appearance. Representative portraits of the Spanish Habsburgs were assessed by 4 investigators for the presence of 11 anatomic features of maxillary deficiency and 7 of mandibular prognathism. Each characteristic was given a binary score of 1 if present and 0 if absent. Thus, the maximum score would be 11 for maxillary deficiency and 7 for mandibular prognathism. A semi‐quantitative scale was established to determine the likelihood of each diagnosis: Maxillary deficiency: 0–4.99 (unlikely), 5–7.99 (likely), 8–11 (very likely); mandibular prognathism: 0–2.99 (unlikely), 3–5.99 (likely), 6–7 (very likely). Six of 7 Habsburg rulers were considered either likely or very likely to have maxillary deficiency, whereas 3/7 were assessed as likely and 4 unlikely to have mandibular prognathism. The results of this study suggest that the primary deformity of the “Habsburg Jaw” is maxillary deficiency rather than absolute mandibular prognathism. © 2014 Wiley Periodicals, Inc.
Contribution of RIT1 mutations to the pathogenesis of Noonan syndrome: Four new cases and further evidence of heterogeneity
Authors: Gos Monika , Fahiminiya Somayyeh , Poznański Jarosław , Klapecki Jakub , Obersztyn Ewa , Piotrowicz Małgorzata , Wierzba Jolanta , Posmyk Renata , Bal Jerzy , Majewski Jacek
Published: June 2014

Noonan syndrome (NS) is a common developmental disorder presenting with dysmorphic craniofacial features, heart defects, and short stature. It belongs to the group of RASopathies caused by germline mutations in genes encoding proteins involved in the RAS/MAPK signaling pathway. Although mutations in nine genes are known to cause NS, approximately 30% of the cases still have unexplained etiology. To identify the new causative genes, 42 patients with a clinical diagnosis of NS, who had negative results on Sanger sequencing of PTPN11, SOS1, and RAF1 (the most common NS genes), were selected for whole exome sequencing. In two patients, mutations in recently described new NS gene—RIT1 were found (c.244T>G [p.Phe82Val] and c.270G>C [p.Met90Ile]). Further analysis of a larger cohort (n = 64) of NS patients with classic Sanger sequencing revealed the presence of RIT1 mutation c.284G>C (p.Gly95Ala) in two additional patients. All the detected mutations were localized in switch II domain responsible for GTPase activity. The modeling of RIT1 protein structure revealed that the mutated amino acids and their interacting residues are evolutionary conserved and any residue replacement might change the structural stability and/or protein internal dynamics influencing catalytic activity of the protein. It seems that the identified mutations might alter protein function and therefore, the activity of ERK and P38 MAPK pathways, thus underlying the specific phenotype observed in NS patients. Our study independently confirms the role of RIT1 in the pathogenesis of Noonan syndrome. © 2014 Wiley Periodicals, Inc.
Ein 2,6‐Bis(phenylamino)pyridinato‐Titan‐Katalysator für die hoch regioselektive Hydroaminoalkylierung von Styrolen und 1,3‐Butadienen
Authors: Dörfler Jaika , Preuß Till , Schischko Alexandra , Schmidtmann Marc , Doye Sven
Published: June 2014

Die über eine C‐C‐Bindungsknüpfung verlaufende katalytische Hydroaminoalkylierung von terminalen Alkenen, 1,3‐Dienen und Styrolen ermöglicht eine direkte und zu 100 % atomökonomische Synthese von Aminen, bei der zwei Regioisomere (linear und verzweigt) gebildet werden können. Hier berichten wir über einen neuen Titan‐Katalysator mit 2,6‐Bis(phenylamino)pyridinato‐Liganden, in dessen Gegenwart die intermolekulare Hydroaminoalkylierung von Styrolen und 1‐Phenyl‐1,3‐butadienen mit exzellenten Regioselektivitäten zugunsten des linearen Produktes erreicht werden kann.
Brønsted‐Säure‐katalysierte konjugierte Addition von β‐Dicarbonylverbindungen an in situ erzeugte ortho‐Chinomethide – enantioselektive Synthese von 4‐Aryl‐4H‐chromenen
Authors: El‐Sepelgy Osama , Haseloff Stefan , Alamsetti Santosh Kumar , Schneider Christoph
Published: June 2014

4H‐Chromene sind wichtige Strukturelemente vieler Naturstoffe und biologisch aktiver Verbindungen. Mithilfe einer enantioselektiven konjugierten Addition von β‐Diketonen an in situ erzeugte ortho‐Chinomethide gelingt nach dehydratisierender Cyclisierung eine breit anwendbare und hochselektive Synthese wertvoller 4‐Aryl‐4H‐chromene. Eine Binol‐basierte chirale Phosphorsäure wird zur In‐situ‐Erzeugung der ortho‐Chinomethide aus ortho‐Hydroxybenzhydrylalkoholen eingesetzt und katalysiert den C‐C‐bindungsbildenden Schritt.
Metallfreie Anellierung von Arenen mit 2‐Aminopyridin‐Derivaten: die Methylgruppe als spurlose nichtchelatisierende dirigierende Gruppe
Authors: Manna Srimanta , Matcha Kiran , Antonchick Andrey P.
Published: June 2014

Eine neue Anellierungsreaktion zwischen 2‐Aminopyridin‐Derivaten und Arenen unter metallfreien Bedingungen wurde beschrieben. Die intermolekulare Transformation ermöglicht den unkomplizierten Zugang zu dem wichtigen Pyrido[1,2‐a]benzimidazol‐Gerüst unter milden Reaktionsbedingungen. Über die beispiellose Anwendung der Methylgruppe von Methylbenzolen als spurlose nichtchelatisierende und hoch regiodirigierende Gruppe wird berichtet.
Multisite Organic–Inorganic Hybrid Catalysts for the Direct Sustainable Synthesis of GABAergic Drugs
Authors: Leyva‐Pérez Antonio , García‐García Pilar , Corma Avelino
Published: June 2014

Multisite organic–inorganic hybrid catalysts have been prepared and applied in a new general, practical, and sustainable synthetic procedure toward industrially relevant GABA derivatives. The domino sequence is composed of seven chemical transformations which are performed in two one‐pot reactions. The method produces both enantiomeric forms of the product in high enantiopurity as well as the racemate in good yields after a single column purification step. This protocol highlights major process intensification, catalyst recyclability, and low waste generation.
Efficacy and Safety of Adalimumab as the First and Second Biologic Agent in Juvenile Idiopathic Arthritis: The German Biologics JIA Registry
Authors: Schmeling Heinrike , Minden Kirsten , Foeldvari Ivan , Ganser Gerd , Hospach Tony , Horneff Gerd
Published: June 2014

Objective

To evaluate the efficacy and safety of adalimumab in patients with juvenile idiopathic arthritis (JIA).

Methods

Baseline demographic and clinical characteristics and disease activity parameters were prospectively documented in the German Biologics JIA Registry. Efficacy was determined using the American College of Rheumatology (ACR) Pediatric (Pedi) response criteria and the Juvenile Arthritis Disease Activity Score based on a 10‐joint count (JADAS‐10). Safety assessments were based on adverse event reports from the responsible physician.

Results

Two hundred eighty‐nine patients with a total of 1,046 visits were identified (435.7 patient‐years). A high proportion of patients demonstrated a significant response to treatment, with a marked decrease in the JADAS‐10 score in both the biologics‐naive group (which consisted of patients who had not received therapy with a biologic agent prior to initiation of adalimumab) and the biologic‐switcher group (which consisted of patients who had been treated with a different biologic agent prior to initiation of adalimumab). The median JADAS‐10 score at treatment start was significantly higher in the biologics‐naive group than in the biologic‐switcher group (12.9 versus 8.5; P = 0.00044), although the score in the biologics‐naive group was lower over the course of adalimumab treatment. ACR Pedi 30, 50, 70, and 90 scores were achieved in 63.4%, 61.0%, 48.8%, and 34.2% of biologics‐naive patients, respectively, at 6 months of treatment, while ACR Pedi 30, 50, 70, and 90 scores were achieved in 47.6%, 38.1%, 21.9%, and 15.2% of biologic‐switcher patients, respectively. Forty‐eight patients experienced 222 adverse events (50.9 per 100 patient‐years). Eleven were reported as serious (2.5 per 100 patient‐years). No malignancies were observed during adalimumab exposure. There were 16 uveitis flares in 11 patients. Treatment was discontinued in 58 patients for the following reasons: inefficacy 11.1%, adverse events 5.2%, remission 4.5%, patient request 11.8%, and other reasons 7.9%.

Conclusion

Adalimumab appears to be highly effective in children and adolescents with JIA who have been previously treated with biologic agents and in children and adolescents who switched biologic agents. The treatment is safe and its efficacy is similar to that of other biologic agents used to treat JIA. Few patients discontinued therapy due to intolerance or inefficacy.
Herpes Zoster and Tofacitinib Therapy in Patients With Rheumatoid Arthritis
Authors: Winthrop Kevin L. , Yamanaka Hisashi , Valdez Hernan , Mortensen Eric , Chew Robert , Krishnaswami Sriram , Kawabata Thomas , Riese Richard
Published: June 2014

Objective

Patients with rheumatoid arthritis (RA) are at increased risk for herpes zoster (HZ) (i.e., shingles). The aim of this study was to determine whether treatment with tofacitinib increases the risk of HZ in patients with RA.

Methods

HZ cases were identified as those reported by trial investigators from the databases of the phase II, phase III, and long‐term extension (LTE) clinical trials in the Tofacitinib RA Development Program. Crude incidence rates (IRs) of HZ per 100 patient‐years (with 95% confidence intervals [95% CIs]) were calculated by exposure group. Logistic regression analyses were performed to evaluate potential risk factors for HZ (e.g., age, prednisone use).

Results

Among 4,789 participants, 239 were identified as having tofacitinib‐associated HZ during the phase II, phase III, and LTE trials, of whom 208 (87%) were female and whose median age was 57 years (range 21–75 years). One HZ case (0.4%) was multidermatomal; none of the cases involved visceral dissemination or death. Twenty‐four patients with HZ (10%) permanently discontinued treatment with tofacitinib, and 16 (7%) were either hospitalized or received intravenous antiviral drugs. The crude HZ IR across the development program was 4.4 per 100 patient‐years (95% CI 3.8–4.9), but the IR was substantially higher within Asia (7.7 per 100 patient‐years, 95% CI 6.4–9.3). Older age was associated with HZ (odds ratio 1.9, 95% CI 1.5–2.6), and IRs for HZ were similar between patients receiving 5 mg tofacitinib twice daily (4.4 per 100 patient‐years, 95% CI 3.2–6.0) and those receiving 10 mg twice daily (4.2 per 100 patient‐years, 95% CI 3.1–5.8). In the phase III trials among placebo recipients, the incidence of HZ was 1.5 per 100 patient‐years (95% CI 0.5–4.6).

Conclusion

In the Tofacitinib RA Development Program, increased rates of HZ were observed in patients treated with tofacitinib compared with those receiving placebo, particularly among patients within Asia. Complicated HZ among tofacitinib‐treated patients was rare.
The impact of image descriptions on user tagging behavior: A study of the nature and functionality of crowdsourced tags
Authors: Lin Yi‐ling , Trattner Christoph , Brusilovsky Peter , He Daqing
Published: June 2014

Crowdsourcing has emerged as a way to harvest social wisdom from thousands of volunteers to perform a series of tasks online. However, little research has been devoted to exploring the impact of various factors such as the content of a resource or crowdsourcing interface design on user tagging behavior. Although images' titles and descriptions are frequently available in image digital libraries, it is not clear whether they should be displayed to crowdworkers engaged in tagging. This paper focuses on offering insight to the curators of digital image libraries who face this dilemma by examining (i) how descriptions influence the user in his/her tagging behavior and (ii) how this relates to the (a) nature of the tags, (b) the emergent folksonomy, and (c) the findability of the images in the tagging system. We compared two different methods for collecting image tags from Amazon's Mechanical Turk's crowdworkers—with and without image descriptions. Several properties of generated tags were examined from different perspectives: diversity, specificity, reusability, quality, similarity, descriptiveness, and so on. In addition, the study was carried out to examine the impact of image description on supporting users' information seeking with a tag cloud interface. The results showed that the properties of tags are affected by the crowdsourcing approach. Tags from the “with description” condition are more diverse and more specific than tags from the “without description” condition, while the latter has a higher tag reuse rate. A user study also revealed that different tag sets provided different support for search. Tags produced “with description” shortened the path to the target results, whereas tags produced without description increased user success in the search task.
Das Wissen der Schulden. Recht, Kulturtechnik und Alltagserfahrung im liberalen Kapitalismus
Authors: Suter Mischa
Published: June 2014

The Knowledge of Debt: Law, Media Technique, and Everyday Experience in Liberal Capitalism. Performing an object such as ‘the economy’ hinges on practices of formatting knowledge. The article proposes to look at such instituting moments in connection with social conflicts over the legitimate rules of exchange. This is exemplified by way of recounting the story of the codification of Swiss bankruptcy law in 1889. In order to homogenize the legal procedures of debt collection and bankruptcy, two subject categories were instituted: ‘merchants’ and ‘non‐merchants’. These different categories were thought to account for the diverging temporalities and spaces of credit exchange in everyday economic life. The introduction of the commercial register, a media‐technical apparatus, enabled a formal distinction between ‘merchants’ and ‘non‐merchants’. However, this boundary was contested and proved to be porose.
Hexacyanoferrate‐adapted biofilm enables the development of a microbial fuel cell biosensor to detect trace levels of assimilable organic carbon (AOC) in oxygenated seawater
Authors: Cheng Liang , Quek Soon Bee , Cord‐Ruwisch Ralf
Published: June 2014

A marine microbial fuel cell (MFC) type biosensor was developed for the detection of assimilable organic carbon (AOC) in ocean water for the purpose of online water quality monitoring for seawater desalination plants prone to biofouling of reverse osmosis (RO) membranes. The anodophilic biofilm that developed on the graphite tissue anode could detect acetate as the model AOC to concentrations as low as 5 µM (120 µg/L of AOC), which is sufficiently sensitive as an online biofouling risk sensor. Although the sensor was operated at a higher (+200 ± 10 mV) than the usual (‐300 mV) anodic potential, the presence of oxygen completely suppressed the electrical signal. In order to overcome this outcompeting effect of oxygen over the anode as electron acceptor by the bacteria, hexacyanoferrate (HCF(III)) was found to enable the development of an adapted biofilm that transferred electrons to HCF(III) rather than oxygen. As the resultant of the reduced HCF(II) could readily transfer electrons to the anode while being re‐oxidised to HCF(III), the marine MFC biosensor developed could be demonstrated to work in the presence of oxygen unlike traditional MFC. The possibility of operating the marine MFC in batch or continuous (in‐line) mode has been explored by using coulombic or potentiometric interpretation of the signal. Biotechnol. Bioeng. 2014;111: 2412–2420. © 2014 Wiley Periodicals, Inc.
Unrelated solubility‐enhancing fusion partners MBP and NusA utilize a similar mode of action
Authors: Raran‐Kurussi Sreejith , Waugh David S.
Published: June 2014

The tendency of recombinant proteins to accumulate in the form of insoluble aggregates in Escherichia coli is a major hindrance to their overproduction. One of the more effective approaches to circumvent this problem is to use translation fusion partners {solubility‐enhancers (SEs)}. E. coli maltose‐binding protein (MBP) and N‐utilization substance A (NusA) are arguably the most effective solubilizing agents that have been discovered so far. Here, we show that although these two proteins are structurally, functionally, and physicochemically distinct, they influence the solubility and folding of their fusion partners in a very similar manner. These SEs act as “holdases” that prevent the aggregation of their fusion partners. Subsequent folding of the passenger proteins, when it occurs, is either spontaneous or chaperone‐mediated. Biotechnol. Bioeng. 2014;111: 2407–2411. © 2014 Wiley Periodicals, Inc.
Structure‐Based Design of New KSP‐Eg5 Inhibitors Assisted by a Targeted Multicomponent Reaction
Authors: Carbajales Carlos , Prado Miguel Ángel , Gutiérrez‐de‐Terán Hugo , Cores Ángel , Azuaje Jhonny , Novio Silvia , Nuñez María Jesús , Fernández‐García Belén , Sotelo Eddy , García‐Mera Xerardo , Sánchez‐Lazo Pedro , Freire‐Garabal Manuel , Coelho Alberto
Published: June 2014

An integrated multidisciplinary approach that combined structure‐based drug design, multicomponent reaction synthetic approaches and functional characterization in enzymatic and cell assays led to the discovery of new kinesin spindle protein (KSP) inhibitors with antiproliferative activity. A focused library of new benzimidazoles obtained by a Ugi+Boc removal/cyclization reaction sequence generated low‐micromolar‐range KSP inhibitors as promising anticancer prototypes. The design and functional studies of the new chemotypes were assessed by computational modeling and molecular biology techniques. The most active compounds—20 (IC50=1.49 μM, EC50=3.63 μM) and 22 (IC50=1.37 μM, EC50=6.90 μM)—were synthesized with high efficiency by taking advantage of the multicomponent reactions.
Calprotectin induces cell death in human prostate cancer cell (LNCaP) through survivin protein alteration
Authors: Sattari Mina , Pazhang Yaghub , Imani Mehdi
Published: June 2014

Calprotectin (CP), an abundant heterodimeric cytosolic protein of neutrophils, conveys a variety of functions such as tumor cell growth arrest and antimicrobial activity. We investigated CP activity and its possible apoptosis‐inducing mechanism of action against an antiandrogen therapy‐resistance prostate cancer cell line LNCaP. Cell viability and Annexin V FITC assays were performed in order to investigate its cell death activity and apoptosis, respectively. In order to address cell death inducing mechanism(s), immunocytochemistry and immunobloting analysis, reactive oxygen species (ROS) and nitric oxide (NO) measurements were performed. The effective concentration of CP against LNCaP promoting LNCaP cell death was 200 µg/mL. ROS and NO levels of cells remarkably were enhanced following treatment with 50 and 100 µg/mL of CP, respectively. Protein expression of anti‐apoptotic protein survivin was significantly decreased after administration of tumor cells with CP. Our data indicate that CP regulates the LNCaP cells viability via survivin‐mediated pathway and ROS and NO enhancement. Thus, inhibition of survivin expression, enhancement of ROS and NO level by CP or other similar pharmaceutical agents might be effective in lowering the malignant proliferation of human prostate cancer cells.
Sarcoma after 5 years of progression‐free survival: Lessons from the French Sarcoma Group
Authors: Choy Edwin
Published: June 2014

Because sarcomas are rare (1% of all adult solid malignancies) and encompass a heterogeneous group of tumors (> 50 subtypes), information regarding late recurrences for patients with resected soft tissue sarcomas, although recognized to occur, is not well defined. Details concerning late recurrences, such as the frequencies, risk factors, and relative rates between tumor subtypes, depend on the existence of a large, well‐annotated, multiinstitutional, accurate database that spans several decades of clinical experience. The French Sarcoma Group has assembled such a database, and they report with accuracy and detail what happens to patients with sarcoma after they survive for > 5 years. Recognition that a significant percentage of long‐term survivors of sarcoma are still at risk of developing late disease recurrence can be paired with the growing awareness that they are also at risk of a shortened lifespan and increased cardiovascular and psychological morbidity to highlight a critical role for long‐term specialty follow‐up.
Long‐term recurrence of soft tissue sarcomas: Prognostic factors and implications for prolonged follow‐up
Authors: Toulmonde Maud , Le Cesne Axel , Mendiboure Jean , Blay Jean‐Yves , Piperno‐Neumann Sophie , Chevreau Christine , Delcambre Corinne , Penel Nicolas , Terrier Philippe , Ranchère‐Vince Dominique , Lae Marick , Le Guellec Sophie , Michels Jean‐Jacques , Robin Yves‐Marie , Bellera Carine , Italiano Antoine
Published: June 2014

BACKGROUND

To the authors' knowledge, the incidence of late recurrence (> 5 years after initial management) is unknown and no prognostic factors for late events have been characterized in patients with soft tissue sarcomas.

METHODS

Follow‐up data from patients with localized soft tissue sarcoma who were included in the French Sarcoma Group database from January 1990 to June 2005 were reviewed. The outcomes of interest were the cumulative probabilities of late (> 5 years) local and metastatic disease recurrence with death as a competing event. Estimations and 95% confidence intervals (95% CIs) were computed with the cumulative incidence function.

RESULTS

A total of 719 patients who were alive and event free > 5 years after their initial diagnosis were included in the current study. Sixty‐seven patients (9.3%) developed a late local recurrence and 42 patients (5.8%) developed a late metastatic recurrence, respectively. On multivariate analysis, internal trunk location (hazard ratio [HR], 3.9; 95% CI, 2.2‐6.7 [P < .001]) and tumor size > 100 mm (HR, 2.1; 95% CI, 1.1‐4 [P = .035]) were the 2 factors found to be independently associated with an increased risk of late local recurrence. Grade > 1 (graded according to the French Federation of Cancer Centers Sarcoma Group) (HR, 4.7; 95% CI 1.1‐21 [P = .04]) was the sole factor found to be independently associated with an increased risk of late metastatic recurrence.

CONCLUSIONS

Late recurrence of soft tissue sarcoma is relatively uncommon. However, the results of the current study emphasize the critical role of long‐term follow‐up to detect late local disease recurrence in patients with retroperitoneal or very large soft tissue sarcomas, and late metastatic recurrence in patients with high‐grade disease. Conversely, the prolonged follow‐up of patients with grade 1 disease is not needed. Cancer 2014;120:3003–3006. © 2014 American Cancer Society.
Cytologic features of parathyroid fine‐needle aspiration on ThinPrep preparations
Authors: Odronic Shelley I. , Reynolds Jordan P. , Chute Deborah J.
Published: June 2014

BACKGROUND

Previous studies have provided cytologic criteria that aid in the recognition of parathyroid tissue on aspirate smears, including high cellularity, the presence of naked nuclei, loose 2‐dimensional clusters, and papillary architecture. However, to the authors knowledge, the cytomorphologic features of parathyroid fine‐needle aspiration (FNA) on liquid‐based preparations have not been previously described.

METHODS

The authors retrospectively reviewed all parathyroid FNAs that had aspirate smears and a ThinPrep preparation performed over 10 years at 1 institution. The FNA smears and ThinPrep preparations from each case were deidentified and independently reviewed for cellularity, naked nuclei, architecture, and colloid‐like material.

RESULTS

Forty patients were included in the current study. When individual cases were compared, the ThinPrep preparation was more likely to have lower cellularity, lack papillary architecture, lack naked nuclei, and have areas with a microfollicular pattern compared with the FNA smear.

CONCLUSIONS

The cytologic features of parathyroid tissue vary depending on preparation. Many of the common features of parathyroid aspirates are lost on ThinPrep preparations, and an increased percentage of parathyroid FNA specimens have a microfollicular pattern on ThinPrep. This may lead to difficulty in recognizing parathyroid origin on FNA. Cancer (Cancer Cytopathol) 2014;122:678–684. © 2014 American Cancer Society.
Established monolayer differentiation of mouse embryonic stem cells generates heterogeneous neocortical‐like neurons stalled at a stage equivalent to midcorticogenesis
Authors: Sadegh Cameron , Macklis Jeffrey D.
Published: June 2014

Two existing and widely applied protocols of embryonic stem (ES) cell differentiation have been developed to enable in vitro generation of neurons resembling neocortical projection neurons in monolayer culture and from embryoid bodies. The monolayer approach offers advantages for detailed in vitro characterizations and potential mechanistic and therapeutic screening. We investigated whether mouse ES cells undergoing largely undirected neocortical differentiation in monolayer culture recapitulate progressive developmental programs of in vivo progenitor and postmitotic differentiation and whether they develop into specific neocortical subtypes. We find that ES‐derived mitotic cells that have been dorsalized by the sonic hedgehog antagonist cyclopamine, and that express, as a total population, cardinal markers of telencephalic progenitors, are, in fact, molecularly heterogeneous. We next show that these progenitors subsequently generate small numbers of heterogeneous neocortical‐like neurons that are “stalled” at an immature stage of differentiation, based on multiple developmental criteria. Although some aspects of neocortical development are recapitulated by existing protocols of ES cell differentiation, these data indicate that mouse ES‐derived neocortical progenitors both are more heterogeneous than their in vivo counterparts and seemingly include many incorrectly specified progenitors. Furthermore, these ES‐derived progenitors spontaneously differentiate into sparse, and incompletely and largely imprecisely differentiated, neocortical‐like neurons that fail to adopt specific neuronal identities in vitro. These results provide both foundation and motivation for refining and enhancing directed differentiation of clinically important neocortical projection neuron subtypes. J. Comp. Neurol. 522:2691–2706, 2014. © 2014 Wiley Periodicals, Inc.
Identity and Culture in Ombudsman Practice
Authors: Brothers Linda M.
Published: June 2014

Most of us in the fields of conflict resolution recognize that we live in an increasingly diverse world, one wherein we seek to understand and resolve conflicts between individuals and groups possessing complex and disparate identities. This article explores the salience of identity and culture within ombuds practice, also referencing recent social science research to examine how implicit bias affects both our understanding of a situation and our conflict resolution strategies. Finally, the article explores possible strategies for isolating and decreasing unconscious ombudsman bias.
Design tables for URM / Hilfsmittel für die praxisnahe Bemessung von unbewehrtem Mauerwerk
Authors: Graubner Carl‐Alexander , Schmitt Michael , Förster Valentin
Published: June 2014

Due to the coming introduction of Eurocode 6 (DIN EN 1996) in Germany many structural engineers ask for design assistances in order to apply the regulations and to accomplish the calculations in a cost‐effective manner. At the same time however, such design tables must result in efficient solutions with respect to the materials used because masonry has to compete with other building materials. This article adresses this issue. Design tables to determine the load bearing capacity using the very simplified and simplified calculation methods in accordance with DIN EN 1996‐3/NA are presented. Additionally diagrams for assessing the required minimum load on external walls exposed to wind loads and for determining the size of basement walls subjected to lateral earth pressure are given. This leads to the conclusion that, in almost all practical cases, it is possible to determine the cross‐section resistance of unreinforced masonry in accordance with Eurocode 6 quickly and effectively while still making the best possible use of the materials employed.