bluuebunny/crossref_metadata_2025 huggingface dataset:
Surtsey and Mount St. Helens: a comparison of early succession rates
Authors: del Moral R. , Magnússon B.
Published: December 2013

Abstract. Surtsey and Mount St. Helens are celebrated, but very different volcanoes. Permanent plots allow comparisons that reveal mechanisms that control succession and its rate and suggest general principles. We estimated rates from structure development, species composition using detrended correspondence analysis (DCA), changes in Euclidean distance (ED) of DCA vectors and by principal components analysis (PCA) of DCA. On Surtsey, rates determined from DCA trajectory analyses decreased as follows: gull colony on lava with sand > gull colony on lava, no sand ≫ lava with sand > sand spit > block lava > tephra. On Mount St. Helens, plots on lahar deposits near woodlands were best developed. The succession rates of open meadows declined as follows: Lupinus-dominated pumice > protected ridge with Lupinus > other pumice and blasted sites > isolated lahar meadows > barren plain. Despite the prominent contrasts between the volcanoes, common themes were revealed. Isolation restricted the number of colonists on Surtsey and to a lesser degree on Mount St. Helens. Nutrient input from outside the system was crucial. On Surtsey, seabirds fashioned very fertile substrates, while on Mount St. Helens wind brought a sparse nutrient rain, then Lupinus enhanced fertility to promote succession. Environmental stress limits succession in both cases. On Surtsey, bare lava, compacted tephra and infertile sands restrict development. On Mount St. Helens, exposure to wind and infertility slow succession.
Projecting flood hazard under climate change: an alternative approach to model chains
Authors: Delgado J. M. , Merz B. , Apel H.
Published: December 2013

Abstract. Flood hazard projections under climate change are typically derived by applying model chains consisting of the following elements: "emission scenario – global climate model – downscaling, possibly including bias correction – hydrological model – flood frequency analysis". To date, this approach yields very uncertain results, due to the difficulties of global and regional climate models to represent precipitation. The implementation of such model chains requires large efforts, and their complexity is high. We propose for the Mekong River an alternative approach which is based on a shortened model chain: "emission scenario – global climate model – non-stationary flood frequency model". The underlying idea is to use a link between the Western Pacific monsoon and local flood characteristics: the variance of the monsoon drives a nonstationary flood frequency model, yielding a direct estimate of flood probabilities. This approach bypasses the uncertain precipitation, since the monsoon variance is derived from large-scale wind fields which are better represented by climate models. The simplicity of the monsoon-flood link allows deriving large ensembles of flood projections under climate change. We conclude that this is a worthwhile, complementary approach to the typical model chains in catchments where a substantial link between climate and floods is found.
Re-appraisal of Scolecopeltidium
Authors: Wu Haixia , Hyde Kevin D.
Published: December 2013

The five new species included in the original circumscription of Scolecopeltidium are re-examined, redescribed, and illustrated. Scolecopeltidium mirabile and S. hormosporum are retained in Scolecopeltidium, while S. liciniae is lectotypified
and transferred to Scolecopeltis, and S. costi and S. multiseptatum are transferred to Micropeltis.
Golovinomyces clematidis sp. nov. from China
Authors: Liu Tiezhi , Wen Jing
Published: December 2013

Golovinomyces clematidis (Erysiphaceae), a new species found on Clematis aethusifolia (Ranunculaceae) in Inner Mongolia, China, is described, illustrated, and compared with morphologically similar species of the G. cichoracearum s. lat. complex.
Four noteworthy hyphomycetes from indoor environments
Authors: Li De-Wei , Zhao Guihua , Yang Chin , Jalsrai Ariunaa , Kerin Brian
Published: December 2013

Four interesting hyphomycetes (Nalanthamala vermoesenii, Parascedosporium putredinis, Stachybotrys elegans, Triadelphia australiensis) have been collected from indoor fungal investigations. Among these fungi, Triadelphia australiensis represents a new record
for Canada and the USA. Parascedosporium putredinis and Stachybotrys elegans are reported for the first time from indoor environments.
Sympodioplanus goaensis sp. nov. from Goa, India
Authors: Pratibha J.
Published: December 2013

A new species, Sympodioplanus goaensis, occurring on decaying unidentified twigs collected from Goa, India, is described and illustrated. The fungus is characterized by numerous conidiogenous cells that are polyblastic, sympodial, integrated, and terminal as well as intercalary
and by naviculiform 1–2-septate conidia
Hygrocybe griseobrunnea, a new brown species from China
Authors: Wang Chao-Qun , Li Tai-Hui , Song Bin
Published: December 2013

Hygrocybe griseobrunnea, a new species in Hygrocybe subsect. Squamulosae, is described and illustrated based on the morphological characters and molecular data. The fungus is characterized by numerous greyish brown to brown or dark brown squamules on the pileus
surface, adnate to shortly decurrent lamellae, and a trichodermal pileipellis.
Spatial data for fungal specimens: retrospective georeferencing and practical recommendations for mycologists
Authors: Braga-Neto Ricardo , Giovanni Renato De , Pezzini Flávia Fonseca , Canhos Dora Ann Lange , Marino Alexandre , Souza Sidnei De , Maia Leonor Costa
Published: December 2013

The number of studies based on herbarium data for analyzing biogeographical patterns and environmental questions is increasing, as herbaria are making their collections available online. However, the quality of a specimen's spatial data still varies dramatically among records. Most
historical specimen records either lack geographic information or have only vague textual descriptions about the locality, while contemporary records may exhibit unwarranted variation in spatial data quality, requiring increased awareness among mycologists about the importance of high quality
primary spatial data for specimens. Georeferencing is the process of assigning geographic coordinates to a record linking it to a geographic location on Earth, and it can be processed retrospectively for records without geographical coordinates based on locality descriptions or directly collected
in the field using GPS handheld units. Here we provide an overview of methods for georeferencing historical data retrospectively, discuss practical recommendations for collecting high quality spatial data for fungal specimens, and suggest decimal degrees as a standard form for citing geographic
coordinates.
Two earth-tongue genera new for Turkey
Authors: Akata Ilgaz , Kaya Abdullah
Published: December 2013

The genera Spathulariopsis (Cudoniaceae) and Trichoglossum (Geoglossaceae) are recorded from Turkey for the first time, based on the collections of Spathulariopsis velutipes and Trichoglossum hirsutum. Short descriptions and photographs of the
taxa are provided.
Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure
Authors: Baker Stephen , Duy Pham Thanh , Nga Tran Vu Thieu , Dung Tran Thi Ngoc , Phat Voong Vinh , Chau Tran Thuy , Turner A Keith , Farrar Jeremy , Boni Maciej F
Published: December 2013

Fluoroquinolones (FQ) are the recommended antimicrobial treatment for typhoid, a severe systemic infection caused by the bacterium Salmonella enterica serovar Typhi. FQ-resistance mutations in S. Typhi have become common, hindering treatment and control efforts. Using in vitro competition experiments, we assayed the fitness of eleven isogenic S. Typhi strains with resistance mutations in the FQ target genes, gyrA and parC. In the absence of antimicrobial pressure, 6 out of 11 mutants carried a selective advantage over the antimicrobial-sensitive parent strain, indicating that FQ resistance in S. Typhi is not typically associated with fitness costs. Double-mutants exhibited higher than expected fitness as a result of synergistic epistasis, signifying that epistasis may be a critical factor in the evolution and molecular epidemiology of S. Typhi. Our findings have important implications for the management of drug-resistant S. Typhi, suggesting that FQ-resistant strains would be naturally maintained even if fluoroquinolone use were reduced.
Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels
Authors: Pless Stephan A , Galpin Jason D , Niciforovic Ana P , Kurata Harley T , Ahern Christopher A
Published: December 2013

Voltage-gated potassium (Kv) channels enable potassium efflux and membrane repolarization in excitable tissues. Many Kv channels undergo a progressive loss of ion conductance in the presence of a prolonged voltage stimulus, termed slow inactivation, but the atomic determinants that regulate the kinetics of this process remain obscure. Using a combination of synthetic amino acid analogs and concatenated channel subunits we establish two H-bonds near the extracellular surface of the channel that endow Kv channels with a mechanism to time the entry into slow inactivation: an intra-subunit H-bond between Asp447 and Trp434 and an inter-subunit H-bond connecting Tyr445 to Thr439. Breaking of either interaction triggers slow inactivation by means of a local disruption in the selectivity filter, while severing the Tyr445–Thr439 H-bond is likely to communicate this conformational change to the adjacent subunit(s).
Genetic and environmental effects affecting the variation in birth date and birth weight of reindeer calves
Authors: Muuttoranta Kirsi , Holand Øystein , Røed Knut H. , Tapio Miika , Nieminen Mauri , Mäki-Tanila Asko
Published: December 2013

The factors causing variation in birth date and birth weight were analysed from the data from an experimental reindeer herd consisting of 1136 calves with parental information. The traits had coefficient of variation of 37 and 14%, respectively. The variation in both traits was affected by year and sex (male calves heavier) and by management factors, such as the age distribution of females and males. Early calving results from the use of older breeding males and is most apparent in prime age females. In both traits the heritability was moderate (0.23 and 0.24) with a high proportion of maternal genetic variation (0.23) in birth weight. The North Atlantic Oscillation (NAO) indices, summarizing the major weather conditions prior to rut, explained part of the annual variation in the traits. The amount of total genetic variation in relation to trait mean, or the evolvability, was 21% in birth date and 10% in birth weight indicating that selection could successfully be used to improve herd productivity and that the traits have substantial potential for adapting to possible changing environmental conditions. The results on genetic correlations imply that selection on calf’s birth weight leads on one hand to calves being born earlier and on the other hand to dams with later parturition.
Analysis of Dose Distribution and Risk of Pneumonitis in Stereotactic Body Radiation Therapy for Centrally Located Lung Tumors
Authors: Kannarunimit Danita , Descovich Martina , Garcia Aaron , Chen Josephine , Weinberg Vivian , Mcguinness Christopher , Pinnaduwage Dilini , Murnane John , Gottschalk Alexander R. , Yom Sue S.
Published: December 2013

Stereotactic body radiation therapy (SBRT) to central lung tumors is associated with normal -tissue toxicity. Highly conformal technologies may reduce the risk of complications. This study compares physical dose characteristics and anticipated risks of radiation pneumonitis (RP) among three SBRT modalities: robotic radiosurgery (RR), helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT). Nine patients with central lung tumors ≤5 cm were compared. RR, HT and VMAT plans were developed per RTOG 0831. Dosimetric comparisons included target coverage, conformity index, heterogeneity index, gradient index, maximal dose at 2 cm from target (D2 cm), and dose-volume parameters for organs at risk (OARs). Efficiency endpoints included total beam-on time and monitor units. RP risk was derived from Lyman-Kutcher-Burman modeling on in-house software. The average GTV and PTV were 11.6 ± 7.86 cm3 and 36.8 ± 18.1 cm3. All techniques resulted in similar target coverage (p = 0.64) and dose conformity (p = 0.88). While RR had sharper fall-off gradient (p = 0.002) and lower D2 cm (p = 0.02), HT and VMAT produced greater homogeneity ( p < 0.001) and delivery efficiency (p = 0.001). RP risk predicted from whole or contralateral lung volumes was less than 10%, but was 2-3 times higher using ipsilateral volumes. Using whole (p = 0.04, p = 0.02) or ipsilateral (p = 0.004, p = 0.0008) volumes, RR and VMAT had a lower risk of RP than HT. Using contralateral volumes, RR had the lowest RP risk (p = 0.0002, p = 0.0003 versus HT, VMAT). RR, HT and VMAT were able to provide clinically acceptable plans following the guidelines provided by RTOG 0813. All techniques provided similar coverage and conformity. RR seemed to produce a lower RP risk for a scenario of small PTV-OAR overlap and small PTV. VMAT and HT produced greater homogeneity, potentially desirable for a large PTV-OAR overlap. VMAT probably yields the lowest RP risk for a large PTV. Understanding subtle differences among these technologies may assist in situations where multiple choices of modality are available.
Global Managerial Skill Sets, Management Development, and The Role of HR: An Exploratory Qualitative Study of North American and Indian Managers
Authors: Ananthram Subramaniam , Nankervis Alan
Published: December 2013

Since Porter’s (1986) seminal study, many researchers have focused on the key factors that assure competitiveness in increasingly global marketplaces, including both business and human resource management (HRM) strategies. With respect to the latter, the importance of developing managers with global skill sets has been a persistent theme in the literature on competitive strategy and HRM over the last decade. This paper extends such research by employing a qualitative methodology to explore the need for and to identify these global skill sets from the perspectives of 56 senior executives from multinational organizations in North America and India. The role of human resource (HR) departments in developing the identified skill-sets for global managers is discussed. The paper also presents the implications for HR professionals and practitioners and provides suggestions for future research.

Keywords: Globalization, Global Mindsets, Human Resource Management, North America, India, Management Development

To cite this document: Subramaniam Ananthram and Alan Nankervis, "Global Managerial Skill Sets, Management Development, and The Role of HR: An Exploratory Qualitative Study of North American and Indian Managers", Contemporary Management Research, Vol.9, No.3, pp.299-322, 2013.

Permanent link to this document:
http://dx.doi.org/10.7903/cmr.9731
Extreme precipitation to increase by nearly 50% by end of century
Authors: Schultz Colin
Published: December 2013

As the atmosphere warms, the air will hold more water. This change, researchers expect, will cause extreme precipitation events to become both stronger and more frequent. A rainfall event that is now considered a 50‐year storm will become more common over the course of the current century. How exactly extreme precipitation events will change, including their regional and seasonal variability, is the focus of much ongoing research.
The late Pliocene Benguela upwelling status revisited by means of multiple temperature proxies
Authors: Leduc Guillaume , Garbe‐Schönberg Dieter , Regenberg Marcus , Contoux Camille , Etourneau Johan , Schneider Ralph
Published: December 2013

As compared to the late Pleistocene, Alkenone‐based sea surface temperature (SST) in the Benguela region revealed relatively warm and stable SST recorded between ∼3.5 and 2.0 Ma, and coincide with a period of increasing biological productivity as revealed by increasing deposition of biogenic opal. We assess how the hydrological patterns recorded in SST proxies are embedded in the geological record by performing a proxy‐proxy comparison. We used Laser‐Ablation Inductively Coupled Plasma‐Mass Spectrometry to measure the Mg/Ca on the planktonic foraminifera species Globigerina bulloides, allowing in situ measurements of Mg/Ca on individual foraminiferal tests. Mg/Ca‐derived temperatures provide much colder temperatures than alkenone‐derived SST by up to 10°C. We build a scenario involving contrasting sensitivities of paleothermometers upon the annual cycle, namely alkenones preferentially capturing SST when the surface ocean is warmer than the mean‐annual average SST, and G. bulloides capturing SST when upwelling intensifies. Multichamber analysis also suggests that G. bulloides migrates below the sea surface while calcifying its last chambers prior to gametogenesis, allowing the extraction of both surface and subsurface temperature from Mg/Ca measured on different chambers. The range of temperatures recorded between our multiple SST proxies is supported by the range of temperatures simulated with a general circulation model when different seasons, different water depth and different orbital configurations occurring during the late Pliocene are considered. A greater seasonal cycle in SST during the Pliocene can account for alkenone and Mg/Ca‐derived temperature contrast, pointing to a radically different mode of upwelling activity in the Benguela region compared to today.
The role of compressional Pc5 pulsations in modulating precipitation of energetic electrons
Authors: Motoba T. , Takahashi K. , Gjerloev J. , Ohtani S. , Milling D. K.
Published: December 2013

Pc5 (1.67–6.67 mHz) magnetic pulsations and the modulation of energetic electron precipitation are often observed simultaneously in the morning auroral‐latitude data. Here we have investigated a conjunction event of Cluster spacecraft and Canadian auroral‐latitude ground stations to identify the role of compressional Pc5 pulsations in modulating precipitation of energetic electrons observed by ground‐based riometers. On 7 December 2002 as the spacecraft moved between L = 4.0 and 6.5 in the dawn sector (0600–0700 magnetic local time (MLT)), we found a monochromatic Pc5 magnetic pulsation at ~4.0 mHz simultaneously in space and on the ground. Both Cluster and ground magnetometer data confirmed that the resonant oscillation at 4.0 mHz occurred around L = ~6.0. Simultaneously, the four Cluster spacecraft identified the compressional Pc5, which was accompanied by similar temporal variations of the fluxes of medium energy (tens to hundreds of keV) electrons and of the intensity of whistler mode chorus waves. While the compressional Pc5 was present in the magnetosphere, the riometers near the spacecraft footprint observed the coincident modulation of electron precipitation at ~4.0 mHz. Our coordinated observations indicate a convincing relationship between compressional Pc5 magnetic pulsations in the magnetosphere and the modulation of electron precipitation in the ionosphere, mediated by chorus waves modulated in the magnetosphere, as predicted by the theory of Coroniti and Kennell []. Around the resonant shell, however, some additional contributions to the modulation of electron precipitation might also come from the effects of the resonant Pc5 oscillation.
Resonant scattering and resultant pitch angle evolution of relativistic electrons by plasmaspheric hiss
Authors: Ni Binbin , Bortnik Jacob , Thorne Richard M. , Ma Qianli , Chen Lunjin
Published: December 2013

We perform a comprehensive analysis to evaluate hiss‐induced scattering effect on the pitch angle evolution and associated decay processes of relativistic electrons. The results show that scattering by the equatorial, highly oblique hiss component is negligible. Quasi‐parallel approximation is good for evaluation of hiss‐driven electron scattering rates ≤ 2 MeV. However, realistic wave propagation angles as a function of latitude must be considered to accurately quantify hiss scattering rates above 2 MeV, and ambient plasma density is also a critical parameter. While the first‐order cyclotron and the Landau resonances are dominant for hiss scattering < 2 MeV electrons, higher‐order resonances become important and even dominant at intermediate pitch angles for ultrarelativistic (≥ 3 MeV) electrons. Hiss‐induced electron pitch angle evolution shows an initially rapid transport from high to lower pitch angles, with a gradual approach toward equilibrium, and a final exponential decay as a whole. Although hiss scattering rates near the loss cone control the pitch angle evolution and the ultimate loss of ultrarelativistic electrons, the scattering bottleneck significantly affects the loss rate and leads to characteristic top hat‐shaped pitch angle distributions at energies < 1 MeV. Decay timescales are on the order of a few days, tens of days, and > 100 days for 500 keV, 2 MeV, and 5 MeV electrons, respectively, consistent with recent observations from the Van Allen Probes and indicating that scattering by hiss can realistically account for the long‐term loss process and the pitch angle evolution of relativistic electrons in the plasmasphere following storm time injections.
Global budget and radiative forcing of black carbon aerosol: Constraints from pole‐to‐pole (HIPPO) observations across the Pacific
Authors: Wang Qiaoqiao , Jacob Daniel J. , Spackman J. Ryan , Perring Anne E. , Schwarz Joshua P. , Moteki Nobuhiro , Marais Eloïse A. , Ge Cui , Wang Jun , Barrett Steven R. H.
Published: December 2013

We use a global chemical transport model (GEOS‐Chem) to interpret aircraft curtain observations of black carbon (BC) aerosol over the Pacific from 85°N to 67°S during the 2009–2011 HIAPER (High‐Performance Instrumented Airborne Platform for Environmental Research) Pole‐to‐Pole Observations (HIPPO) campaigns. Observed concentrations are very low, implying much more efficient scavenging than is usually implemented in models. Our simulation with a global source of 6.5 Tg a−1 and mean tropospheric lifetime of 4.2 days (versus 6.8 ± 1.8 days for the Aerosol Comparisons between Observations and Models (AeroCom) models) successfully simulates BC concentrations in source regions and continental outflow and captures the principal features of the HIPPO data but is still higher by a factor of 2 (1.48 for column loads) over the Pacific. It underestimates BC absorbing aerosol optical depths (AAODs) from the Aerosol Robotic Network by 32% on a global basis. Only 8.7% of global BC loading in GEOS‐Chem is above 5 km, versus 21 ± 11% for the AeroCom models, with important implications for radiative forcing estimates. Our simulation yields a global BC burden of 77 Gg, a global mean BC AAOD of 0.0017, and a top‐of‐atmosphere direct radiative forcing (TOA DRF) of 0.19 W m−2, with a range of 0.17–0.31 W m−2 based on uncertainties in the BC atmospheric distribution. Our TOA DRF is lower than previous estimates (0.27 ± 0.06 W m−2 in AeroCom, 0.65–0.9 W m−2 in more recent studies). We argue that these previous estimates are biased high because of excessive BC concentrations over the oceans and in the free troposphere.
Characterizing tropical overshooting deep convection from joint analysis of CloudSat and geostationary satellite observations
Authors: Takahashi Hanii , Luo Zhengzhao Johnny
Published: December 2013

Tropical overshooting deep convection (ODC) plays an important role in affecting the heat and constituent budgets of the upper troposphere and lower stratosphere. This study investigates the properties and behaviors of such intense deep convection using a combination of CloudSat observations and geostationary satellite data. Our study approaches the subject from two unique perspectives: first, W‐band cloud profiling radar (CPR) observations from CloudSat are used, which add to our knowledge of the internal vertical structure of tropical ODC; second, each snapshot observation from CloudSat is cast into the time evolution of the convective systems through joint analysis of geostationary satellite data, which provides a lifecycle view of tropical ODC. Climatology of tropical ODC based on CloudSat data is first presented and compared with previous works. Various parameters from CloudSat observations pertaining to cloud vertical extent, convective intensity, and convective environment are analyzed. Although results broadly agree with previous studies, we show that CloudSat CPR is capable of capturing both small cloud particles and large precipitation‐size particles, thus presenting a more complete depiction of the internal vertical structure of tropical ODC. Geostationary satellite observations are analyzed in conjunction with CloudSat data to identify the life stage of the convective systems (CSs) in which ODC is embedded. ODC associated with the growing, mature, and dissipating stage of the CSs represents, respectively, 66.2%, 33.4%, and 0.4% of the total population. Convective intensity of the ODC is found to be stronger during the growing stage than the mature stage.
Sociodemographic, Disease, Health System, and Contextual Factors Affecting the Initiation of Biologic Agents in Rheumatoid Arthritis: A Longitudinal Study
Authors: Yelin Edward , Tonner Chris , Kim Seoyoung C. , Katz Jeffrey N. , Ayanian John Z. , Brookhart M. Alan , Solomon Daniel H.
Published: December 2013

Objective

To analyze the effect of sociodemographic, disease, and health system characteristics and contextual features about the community of residence on the subsequent initiation of treatment with biologic agents for rheumatoid arthritis (RA).

Methods

We analyzed data from the University of California, San Francisco Rheumatoid Arthritis Panel Study for the years 1999–2011. Principal data collection was by a structured annual phone survey. We estimated Kaplan‐Meier curves of the time until initiation of biologic agents, stratified by age and income. We also used Cox regression to estimate the effect of individual‐level sociodemographic and medical factors, contextual‐level socioeconomic status measures, and density of health providers in the local community on the probability of initiating therapy with biologic agents for RA.

Results

In total, 527 persons were included in the panel in 1999, and 229 persons (44%) had initiated therapy with biologic agents by 2011. In multivariable Cox regression models, age <70 years (hazard ratio [HR] for ages 19–54 years 1.89 [95% confidence interval (95% CI) 1.24–2.87] and HR for ages 55–69 years 1.25 [95% CI 0.84–1.87]), Hispanic ethnicity (HR 2.02 [95% CI 1.05–3.86]), household income ≥$30,000/year (HR 1.61 [95% CI 1.12–2.32]), being married or with a partner (HR 1.39 [95% CI 1.00–1.92]), and residence in rural environments (HR 1.96 [95% CI 1.28–2.99]) were associated with a higher probability of initiating biologic agents. Having no (HR 0.18 [95% CI 0.08–0.40]) or only 1–4 rheumatology visits in the year prior to interview (HR 0.60 [95% CI 0.45–0.81]) and living in an area with ≥1 federally qualified health centers (HR 0.63 [95% CI 0.41–0.96]) were associated with a lower probability.

Conclusion

The probability of initiating therapy with biologic agents is affected by sociodemographic and health system characteristics as well as the nature of the community of residence, resulting in disparities in access to these medications.
Effect of Methotrexate, Anti–Tumor Necrosis Factor α, and Rituximab on the Immune Response to Influenza and Pneumococcal Vaccines in Patients With Rheumatoid Arthritis: A Systematic Review and Meta‐Analysis
Authors: Hua Charlotte , Barnetche Thomas , Combe Bernard , Morel Jacques
Published: December 2013

Objective

To assess the current literature on the impact of rheumatoid arthritis (RA) treatments on the humoral response to pneumococcal and influenza vaccines.

Methods

We systematically searched the literature for studies evaluating the immune response to vaccines in RA patients receiving methotrexate (MTX) and/or biologic agents. The efficacy of vaccination, assessed by the response rate based on increased antibody titers before and 3–6 weeks after vaccination, was extracted by one investigator and verified by another.

Results

In total, 12 studies were included. RA patients mainly received MTX, anti–tumor necrosis factor α (anti‐TNFα), or rituximab (RTX). Influenza vaccination response was reduced for RTX (43 patients; pooled odds ratio [OR] 0.44 [95% confidence interval (95% CI) 0.17–1.12] for H1N1, OR 0.11 [95% CI 0.04–0.31] for H3N2, and OR 0.29 [95% CI 0.10–0.81] for B) but not for anti‐TNFα (308 patients; OR 0.93 [95% CI 0.36–2.37] for H1N1, OR 0.79 [95% CI 0.34–1.83] for H3N2, and OR 0.79 [95% CI 0.37–1.70] for B). For MTX, results differed depending on the method of analysis (222 patients; OR 0.35 [95% CI 0.18–0.66] for at least 2 strains, ORs were close to 1.0 in the single strain analysis). Pneumococcal vaccination response was reduced for 139 patients receiving MTX compared with controls (OR 0.33 [95% CI 0.20–0.54] for serotype 6B and OR 0.58 [95% CI 0.36–0.94] for 23F) but not for anti‐TNFα (258 patients; OR 0.96 [95% CI 0.57–1.59] for 6B and OR 1.20 [95% CI 0.57–2.54] for 23F). For RTX, the response was reduced (88 patients; OR 0.25 [95% CI 0.11–0.58] for 6B and OR 0.21 [95% CI 0.04–1.05] for 23F).

Conclusion

MTX decreases humoral response to pneumococcal vaccination and may impair response to influenza vaccination. The immune response to both vaccines is reduced with RTX but not with anti‐TNFα therapy in RA patients.
Effect of Certolizumab Pegol on Multiple Facets of Psoriatic Arthritis as Reported by Patients: 24‐Week Patient‐Reported Outcome Results of a Phase III, Multicenter Study
Authors: Gladman D. , Fleischmann R. , Coteur G. , Woltering F. , Mease P. J.
Published: December 2013

Objective

To examine the effect of certolizumab pegol (CZP) on patient‐reported outcomes (PROs) in psoriatic arthritis (PsA) patients with and without prior tumor necrosis factor (TNF) inhibitor exposure.

Methods

The ongoing phase III RAPID‐PsA trial was double blind and placebo controlled to week 24. Patients were randomized 1:1:1 to placebo every 2 weeks or CZP 400 mg at weeks 0, 2, and 4, followed by either CZP 200 mg every 2 weeks or CZP 400 mg every 4 weeks. PRO measures evaluated were the Health Assessment Questionnaire (HAQ) disability index (DI), health status (measured by the Short Form 36 [SF‐36] health survey), Psoriatic Arthritis Quality of Life (PsAQOL), Fatigue Assessment Scale, patient assessment of pain (visual analog scale), and Dermatology Life Quality Index (DLQI). Post hoc analyses of PROs in patients with and without prior TNF inhibitor exposure were conducted. Change from baseline for all PROs was analyzed for the randomized population using analysis of covariance with last observation carried forward imputation.

Results

A total of 409 patients were randomized. Twenty percent had received a prior TNF inhibitor. Baseline demographics were similar between the treatment groups. At week 24, clinically meaningful differences in HAQ DI, SF‐36, PsAQOL, fatigue, pain, and DLQI were observed in both CZP arms versus placebo (P < 0.001), irrespective of prior TNF inhibitor exposure. More CZP‐treated patients reached SF‐36 general population norms than placebo‐treated patients.

Conclusion

Both CZP dosing schedules provided rapid improvements in PROs across multiple disease aspects in patients with PsA. The benefits of CZP treatment for health‐related quality of life were seen across generic, PsA‐specific, and dermatology‐specific measures and were observed in patients regardless of prior TNF inhibitor exposure.
Peripheral Neuropathies in Systemic Lupus Erythematosus: Clinical Features, Disease Associations, and Immunologic Characteristics Evaluated Over a Twenty‐Five–Year Study Period
Authors: Oomatia A. , Fang H. , Petri M. , Birnbaum J.
Published: December 2013

Objective

To characterize peripheral neuropathy subtypes, ancillary studies, and immunologic profiles associated with peripheral neuropathies in patients with systemic lupus erythematosus (SLE).

Methods

In this 25‐year study of 2,097 SLE patients, we characterized peripheral neuropathies due to SLE and compared clinical and SLE‐related features in patients with versus those without neuropathy.

Results

The prevalence of peripheral neuropathies was 5.9% (123 of 2,097 patients), and 66.7% of these patients (82 of 123) had peripheral neuropathies attributable to SLE. We noted that 17.1% of the patients with peripheral neuropathies due to SLE (14 of 82 patients) had small‐fiber neuropathy, which is a painful neuropathy not included in the American College of Rheumatology (ACR) neuropsychiatric SLE (NPSLE) case definitions. SLE patients with small‐fiber neuropathies could present with unorthodox neuropathic pain patterns not consistent with a stocking–glove distribution and had associated skin biopsy results suggestive of dorsal root ganglion neuronal cell loss. Compared to SLE patients without peripheral neuropathies, those with peripheral neuropathies had lower mean disease activity (P = 0.01) and higher disease damage (P < 0.01) and were more likely to have a history of herpes zoster virus infection (P < 0.01), osteoporotic fractures (P < 0.01), and opportunistic infections (P < 0.01).

Conclusion

Our findings indicate that small‐fiber neuropathy is a frequently occurring peripheral neuropathy. The skin biopsy findings in small‐fiber neuropathy patients support the notion that distinct mechanisms target the dorsal root ganglia as well as distal axons. SLE patients with peripheral neuropathy have lower mean disease activity scores and higher disease damage. Our findings suggest that revision of the ACR NPSLE case definitions, which currently do not include small‐fiber neuropathies, is warranted.
Regulation of Apoptosis and Inflammatory Responses by Insulin‐like Growth Factor Binding Protein 3 in Fibroblast‐like Synoviocytes and Experimental Animal Models of Rheumatoid Arthritis
Authors: Lee Hwa‐Suk , Woo Seong Ji , Koh Hyoung‐Won , Ka Sun‐O , Zhou Lu , Jang Kyu Yun , Lim Hye Song , Kim Hyun‐Ok , Lee Sang‐Il , Park Byung‐Hyun
Published: December 2013

Objective

Insulin‐like growth factor binding protein 3 (IGFBP‐3) is known to interfere with the NF‐κB signaling pathway, and it effectively promotes apoptosis in tumor cells by a variety of mechanisms. NF‐κB activation and apoptosis resistance of fibroblast‐like synoviocytes (FLS) play pivotal roles in rheumatoid arthritis (RA). This study was undertaken to evaluate whether IGFBP‐3 has antiarthritic effects.

Methods

To deliver IGFBP‐3, we used an adenovirus containing IGFBP‐3 complementary DNA (AdIGFBP‐3) or IGFBP‐3 mutant that is devoid of IGF binding affinity but retains IGFBP‐3 receptor binding ability (AdmtIGFBP‐3). The regulatory roles of IGFBP‐3 in inflammation and bone destruction were investigated in mice with collagen‐induced arthritis (CIA).

Results

IGFBP‐3 levels were significantly higher in patients with RA than in those with osteoarthritis (OA) and were notably higher in patients with active RA. AdIGFBP‐3 suppressed NF‐κB activation, chemokine production, and matrix metalloproteinase secretion induced by tumor necrosis factor α (TNFα) in RA FLS. AdIGFBP‐3 sensitized RA FLS to TNFα‐induced apoptosis in vitro and also significantly increased apoptosis in an in vivo model of Matrigel implants engrafted into immunodeficient mice. AdIGFBP‐3–injected mice with CIA had attenuated arthritis severity and reduced radiologic and pathologic abnormalities. Moreover, AdIGFBP‐3 down‐regulated local and systemic levels of NF‐κB–targeted proinflammatory cytokines. Of note, RA FLS and mice with CIA treated with AdmtIGFBP‐3 exhibited similar effects as those treated with AdIGFBP‐3.

Conclusion

Our results suggest that both the inflammatory response and bone destruction are reduced with blockage of NF‐κB activation and induction of apoptosis in RA FLS by IGFBP‐3. Therefore, IGFBP‐3 may have therapeutic potential in RA.
Fcγ Receptor III and Fcγ Receptor IV on Macrophages Drive Autoimmune Valvular Carditis in Mice
Authors: Hobday Patricia M. , Auger Jennifer L. , Schuneman Gregory R. , Haasken Stefanie , Verbeek J. Sjef , Binstadt Bryce A.
Published: December 2013

Objective

Arthritis and valvular carditis coexist in several human rheumatic diseases, including systemic lupus erythematosus, rheumatic fever, and rheumatoid arthritis. T cell receptor–transgenic K/BxN mice develop spontaneous autoantibody‐associated arthritis and valvular carditis. The common Fc receptor γ (FcRγ) signaling chain is required for carditis to develop in K/BxN mice. FcRγ pairs with numerous receptors in a variety of cells. The aim of this study was to identify the FcRγ‐associated receptors and Fcγ receptor (FcγR)–expressing cells that mediate valvular carditis in this model.

Methods

We bred K/BxN mice lacking the genes that encode activating Fcγ receptors (FcγRI, FcγRIII, and FcγRIV), and we assessed these mice for valvular carditis. We similarly evaluated complement component C3–deficient K/BxN mice. Immunohistochemistry, bone marrow transplantation, and macrophage depletion were used to define the key FcRγ‐expressing cell type.

Results

Genetic deficiency of only one of the activating Fcγ receptors did not prevent carditis, whereas deficiency of all 3 activating Fcγ receptors did. Further analysis demonstrated that FcγRIII and FcγRIV were the key drivers of valve inflammation; FcγRI was dispensable. C3 was not required. FcRγ expression by radioresistant cells was critical for valvular carditis to develop, and further analysis indicated that macrophages were the key candidate FcγR‐expressing effectors of carditis.

Conclusion

FcγRIII and FcγRIV act redundantly to promote valvular carditis in K/BxN mice with systemic autoantibody‐associated arthritis. Macrophage depletion reduced the severity of valve inflammation. These findings suggest that pathogenic autoantibodies engage Fcγ receptors on macrophages to drive valvular carditis. Our study provides new insight into the pathogenesis of cardiovascular inflammation in the setting of autoantibody‐associated chronic inflammatory diseases.
Interleukin‐21 Receptor Deficiency Increases the Initial Toll‐like Receptor 2 Response but Protects Against Joint Pathology by Reducing Th1 and Th17 Cells During Streptococcal Cell Wall Arthritis
Authors: Marijnissen Renoud J. , Roeleveld Debbie M. , Young Deborah , Nickerson‐Nutter Cheryl , Abdollahi‐Roodsaz Shahla , Garcia de Aquino Sabrina , van de Loo Fons A. J. , van Spriel Annemiek B. , Boots Annemieke M. H. , van den Berg Wim B. , Koenders Marije I.
Published: December 2013

Objective

The cytokine interleukin‐21 (IL‐21) can have both proinflammatory and immunosuppressive effects. The purpose of this study was to investigate the potential dual role of IL‐21 in experimental arthritis in relation to Th17 cells.

Methods

Antigen‐induced arthritis (AIA) and chronic streptococcal cell wall (SCW) arthritis were induced in IL‐21 receptor–deficient (IL‐21R−/−) and wild‐type mice. Knee joints, synovial tissue, and serum were analyzed for arthritis pathology and inflammatory markers.

Results

During AIA and chronic SCW arthritis, IL‐21R deficiency protected against severe inflammation and joint destruction. This was accompanied by suppressed serum IgG1 levels and antigen‐specific T cell responses. Levels of IL‐17 were reduced during AIA, and synovial lymphocytes isolated during SCW arthritis for flow cytometry demonstrated that mainly IL‐17+ interferon‐γ (IFNγ)–positive T cells were reduced in IL‐21R−/− mice. However, during the acute phases of SCW arthritis, significantly higher joint swelling scores were observed, consistent with enhanced tumor necrosis factor and IL‐6 expression. Interestingly, IL‐21R−/− mice were significantly less capable of up‐regulating suppressor of cytokine signaling 1 (SOCS‐1) and SOCS‐3 messenger RNA. IL‐21 stimulation also affected the Toll‐like receptor 2 (TLR‐2)/caspase recruitment domain 15 response to SCW fragments in vitro, indicating that impaired SOCS regulation in the absence of IL‐21 signaling might contribute to the increased local activation during SCW arthritis.

Conclusion

In contrast to the proinflammatory role of IL‐21 in adaptive immunity, which drives IL‐17+IFN+ cells and joint pathology during chronic experimental arthritis, IL‐21 also has an important immunosuppressive role, presumably by inhibiting TLR signaling via SOCS‐1 and SOCS‐3. If this dual role of IL‐21 in various immune processes is present in human disease, it could make IL‐21 a difficult therapeutic target in rheumatoid arthritis.
Progress in the management of limited‐stage small cell lung cancer
Authors: Amini Arya , Byers Lauren A. , Welsh James W. , Komaki Ritsuko U.
Published: December 2013

Approximately 15% of lung cancer cases are of the small cell subtype, but this variant is highly aggressive and is often diagnosed at advanced stages. Outcomes after current treatment regimens have been poor, with 5‐year survival rates as low as 25% for patients with limited‐stage disease. Advances in therapy for small cell lung cancer have included the development of more effective chemotherapeutic agents and radiation techniques. For example, hyperfractionated radiotherapy given early in the course of the disease can reduce local recurrence and extend survival. Other technologic advances in radiation planning and delivery such as intensity‐modulated radiotherapy, image‐guided adaptive radiotherapy, and 4‐dimensional computed tomography/positron emission tomography have facilitated the design of treatment volumes that closely conform to the shape of the tumor, which allows higher radiation doses to be given while minimizing radiation‐induced toxicity to adjacent structures. Future improvements in outcomes will require clarifying the molecular basis for this disease. Cancer 2014;120:790–798. © 2013 American Cancer Society.
Range dynamics, rather than convergent selection, explain the mosaic distribution of red‐winged blackbird phenotypes
Authors: Dufort Matthew J. , Keith Barker F.
Published: December 2013

Geographic distributions of genetic and phenotypic characters can illuminate historical evolutionary processes. In particular, mosaic distributions of phenotypically similar populations can arise from parallel evolution or from irregular patterns of dispersal and colonization by divergent forms. Two phenotypically divergent forms of the red‐winged blackbird (Agelaius phoeniceus) show a mosaic phenotypic distribution, with a “bicolored” form occurring disjunctly in California and Mexico. We analyzed the relationships among these bicolored populations and neighboring typical populations, using ~600 bp of mitochondrialDNAsequence data and 10 nuclear short tandem repeat loci. We find that bicolored populations, although separated by ~3000 km, are genetically more similar to one other than they are to typical populations separated by ~400 km. We also find evidence of ongoing gene flow among populations, including some evidence of asymmetric gene flow. We conclude that the current distribution of bicolored forms represents incomplete speciation, where recent asymmetric hybridization with typicalA. phoeniceusis dividing the range of a formerly widespread bicolored form. This hypothesis predicts that bicolored forms may suffer extinction by hybridization. Future work will use fine‐scaled geographical sampling and nuclear sequence data to test for hybrid origins of currently typical populations and to more precisely quantify the directionality of gene flow.
Efficient Synthetic Approach to Substituted Benzo[b]furans and Benzo[b]thiophenes by Iodine‐Promoted Cyclization of Enaminones
Authors: Labarrios Ehecatl , Jerezano Alberto , Jiménez Fabiola , del Carmen Cruz María , Delgado Francisco , Zepeda L. Gerardo , Tamariz Joaquín
Published: December 2013

An efficient synthetic approach to the substituted benzo[b]furan and benzo[b]thiophene scaffolds by iodine‐mediated cyclization of the corresponding enaminones is described. This protocol was applied to a large series of these latter precursors to afford the respective benzoheterocycles substituted at the C‐2 position by a carbonyl group functionality. A study of the factors that control this process reveals that the reactivity depends on the presence of electron‐donor groups in the aryl ring of the aryloxycarbonylic and arylthiocarbonylic moieties.
Microvascularization and histomorphology of lateral line organs in adult Xenopus laevis
Authors: Gerlach Nicolas , Minnich Bernd , Lametschwandtner Alois
Published: December 2013

The microvasculariaztion of the lateral line organs (LLOs) of the adult pipid frog, Xenopus laevis was studied by scanning electron microscopy of vascular corrosion casts (VCCs) and correlative light microscopy of paraplast embedded tissues sections. Scanning electron micrographs of VCCs revealed that each neuromast within the LLO rests on a distinct bowl‐like capillary network (vascular bowl). One to three vascular bowls were supplied by an ascending arteriole and drained by a descending venule towards the skin deep dermal vascular network. Blood flow regulation mechanisms in form of intimal cushions were present at the origin of ascending arterioles supplying LLOs, microvenous valves were present at the confluence of deep dermal venules and veins. This together with sprouting and nonsprouting angiogenesis (intussusceptive microvascular growth) found in vascular bowls demonstrate that in adult Xenopus the capillary bed of LLO's still can be adjusted to changing energetic needs. J. Morphol. 275:497–503, 2014. © 2013 Wiley Periodicals, Inc.
Effect of AC current on corrosion behavior of cathodically protected Q235 steel
Authors: Tang D. Z. , Du Y. X. , Lu M. X. , Jiang Z. T. , Dong L. , Wang J. J.
Published: December 2013

A self‐designed experiment circuit was adopted to investigate the effect of alternating current (AC) on corrosion rate and cathodic protection (CP) potential of cathodically protected Q235 steel in the simulated soil solution of 4 g/L sodium sulfate. It is found that the corrosion induced by AC current can be controlled by increasing CP current when AC current density is below 300 A/m2. However, in case that CP current is too large the corrosion of Q235 steel will be accelerated. Moreover, CP potential of Q235 steel shifts considerably due to AC current and the shift direction depends on the applied CP current. Based on the experimental results, a combination role of CP current and AC current considering micro‐electrons transfer is introduced to explore the mechanism of AC corrosion.
Novel IFT122 mutation associated with impaired ciliogenesis and cranioectodermal dysplasia
Authors: Alazami Anas M. , Seidahmed Mohammed Zain , Alzahrani Fatema , Mohammed Adam O. , Alkuraya Fowzan S.
Published: December 2013

Cranioectodermal dysplasia (CED) is a very rare autosomal recessive disorder characterized by a recognizable craniofacial profile in addition to ectodermal manifestations involving the skin, hair, and teeth. Four genes are known to be mutated in this disorder, all involved in the ciliary intraflagellar transport confirming that CED is a ciliopathy. In a multiplex consanguineous family with typical CED features in addition to intellectual disability and severe cutis laxa, we used autozygosity‐guided candidate gene analysis to identify a novel homozygous mutation in IFT122, and demonstrated impaired ciliogenesis in patient fibroblasts. This report on IFT122 broadens the phenotype of CED and expands its allelic heterogeneity.
Rectilinear m‐Center problem
Authors: Ko M. T. , Lee R. C. T. , Chang J. S.
Published: December 2013

In this article we consider the unweighted m‐center problem with rectilinear distance. We preent an O(nm–2 log n) algorithm for the m‐center problem where m ≥ 4.