bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of pateclizumab (anti-lymphotoxin-α) compared to adalimumab in rheumatoid arthritis: a head-to-head phase 2 randomized controlled study (The ALTARA Study)
Authors: Kennedy William P , Simon J Abraham , Offutt Carolyn , Horn Priscilla , Herman Ann , Townsend Michael J , Tang Meina T , Grogan Jane L , Hsieh Frank , Davis John C 
Published: October 2014

Abstract
Introduction
Tumor necrosis factor (TNF) and, possibly, lymphotoxin alpha (LTα) signaling contribute to inflammation and rheumatoid arthritis (RA) pathogenesis. Pateclizumab (anti-lymphotoxin- alpha; MLTA3698A) is a humanized monoclonal antibody that blocks and depletes anti-LTα. This phase 2, randomized, head-to-head, active- and placebo-controlled trial examined the safety and efficacy of pateclizumab compared to adalimumab in RA patients with an inadequate response to disease-modifying antirheumatic drugs (DMARD-IR).

Methods
Patients (n = 214) with active RA (-6 swollen and tender joints, C-reactive protein -10 mg/L) on oral DMARDs were randomized (2:2:1) to receive pateclizumab 360 mg, adalimumab 40 mg, or placebo subcutaneously every 2 weeks. The primary endpoint, 4-variable, 28-joint disease activity score erythrocyte sedimentation rate (DAS28(4)-ESR) response, was evaluated at 12 weeks using an analysis of covariance (ANCOVA) model with adjustments for concomitant DMARD use and geographic region. Secondary efficacy endpoints included American College of Rheumatology (ACR) 20, ACR50, and ACR70 responses at Day 85. Pharmacokinetics, pharmacodynamics, and immunogenicity of pateclizumab were assessed.

Results
Pateclizumab reduced the DAS28(4)-ESR response (-1.89) at 12 weeks, however, this did not reach statistical significance compared to placebo (-1.54), while adalimumab (-2.52) differed significantly from both placebo and pateclizumab. Pateclizumab 12-week ACR20, ACR50 and ACR70 response rates (64%, 33%, and 14%) suggested clinical activity but were not statistically significant compared to placebo rates (46%, 24%, and 8%, respectively). CXCL13 serum levels decreased significantly following pateclizumab and adalimumab administration, demonstrating pharmacological target engagement by both drugs. Overall, adverse events (AEs) were comparable among all cohorts. Infections were the most common AE, occurring with comparable frequency in all groups. Serious AEs occurred in 0% of pateclizumab, 5.9% of adalimumab, and 2.3% of placebo patients, with serious infection in 2.3% of adalimumab patients and none in pateclizumab and placebo patients.

Conclusions
Pateclizumab had a good safety profile in patients inadequately responsive to DMARDs, but no statistically significant improvement in RA signs and symptoms after 12 weeks of treatment. Adalimumab demonstrated efficacy and safety comparable to published results in this head-to-head comparison in DMARD-IR RA patients.

Trial registration
ClinicalTrials.gov NCT01225393NCT01225393, Registered 18 October 2010.
Nociceptive neurons detect cytokines in arthritis
Authors: Schaible Hans-Georg 
Published: October 2014

AbstractProinflammatory cytokines are major mediators in the pathogenesis of diseases of joints such as rheumatoid arthritis and osteoarthritis. This review emphasizes that proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1beta, interleukin-6 and interleukin-17 are also mediators of pain by directly acting on the nociceptive system. Proportions of nociceptive sensory neurons express receptors for these cytokines, and the application of cytokines rapidly changes the excitability, ion currents and second messenger systems of these neurons. By inducing persistent sensitization of nociceptive sensory neurons (C- and a proportion of Aδ-fibers) for mechanical stimuli in the joint (a process called peripheral sensitization), these cytokines significantly contribute to the persistent hyperalgesia typical for many disease states of the joint. In addition, the disease-associated release of cytokines in the spinal cord supports the generation of central sensitization. The therapeutic neutralization of proinflammatory cytokines thus not only reduces the process of inflammation but may directly reduce hyperalgesia and pain by reversing the neuronal effects of cytokines. It is emerging that different cytokines have different actions on neurons. The neutralization of tumor necrosis factor-alpha reduces both mechanical and thermal hyperalgesia of the joint. The neutralization of interleukin-1beta attenuates thermal hyperalgesia whereas the neutralization of interleukin-6 and interleukin-17 mainly reduces mechanical hyperalgesia. These different effects are partly explained by influencing different target molecules in sensory neurons. For example, in cultured sensory neurons tumor necrosis factor-alpha and interleukin-1beta upregulate the TRPV1 ion channel, which is involved in the transduction of heat stimuli, consistent with an effect of these cytokines in thermal hyperalgesia. By contrast, interleukin-17 upregulates the TRPV4 ion channel, which has a role in the transduction of mechanical stimuli. Thus, the analgesic potential of neutralizing cytokines seems to depend on which cytokine is mainly involved in the particular pain state.
Image-guided radiotherapy of the prostate using daily CBCT: the feasibility and likely benefit of implementing a margin reduction
Authors: Maund I F , Benson R J , Fairfoul J , Cook J , Huddart R , Poynter A 
Published: October 2014

Objective:
To investigate whether planning target volume (PTV) margins may be safely reduced in radiotherapy of localized prostate cancer incorporating daily online tube potential-cone beam CT (CBCT) image guidance and the anticipated benefit in predicted rectal toxicity.

Methods:
The prostate-only clinical target volume (CTV2) and rectum were delineated on 1 pre-treatment CBCT each week in 18 randomly selected patients. By transposing these contours onto the original plan, dose–volume histograms (DVHs) for CTV2 and the rectum were each calculated and combined, for each patient, to produce a single mean DVH representative of the dose delivered over the treatment course. Plans were reoptimized using reduced CTV2 to PTV2 margins and the consequent radiobiological impact modelled by the tumour control probability (TCP) and normal tissue complication probability (NTCP) of the rectum.

Results:
All CBCT images were deemed of sufficient quality to identify the CTV and rectum. No loss of TCP was observed when plans using the standard 5-mm CTV2 to PTV2 margin of the centre were reoptimized with a 4- or 3-mm margin. Margin reduction was associated with a significant decrease in rectal NTCP (5–4 mm; p &lt; 0.05 and 5–3 mm; p &lt; 0.01).

Conclusion:
Using daily online image guidance with CBCT, a reduction in CTV2 to PTV2 margins to 3 mm is achievable without compromising tumour control. The consequent sparing of surrounding normal tissues is associated with reduced anticipated rectal toxicity.

Advances in knowledge:
Margin reduction is feasible and potentially beneficial. Centres with image-guided radiotherapy capability should consider assessing whether margin reduction is possible within their institutes.
Debate: Lessons Learnt from 10 Years and USD 50 million of Grant Making to End Human Trafficking
Authors: Newcomb Randy 
Published: October 2014

On 26 September 2013, Humanity United, with our partners Legatum Foundation and Walk Free, announced the creation of the USD 100 million Freedom Fund to combat human trafficking around the world. This fund is the first of its kind, organised by three private foundations and borne in part from Humanity United’s experience as a donor over the past decade, during which time we provided more than USD 50 million to fund anti-trafficking efforts globally.During this time, we also worked closely with the donor community as well as organisations and activists working on the frontlines of the struggle to end human trafficking. Over this period, four themes have emerged that help us better understand how to more effectively work and provide grants to combat human trafficking.
Efficacy, safety, and tolerability of IVIG-SN in patients with primary immunodeficiency
Authors: Stein Mark R. , Wasserman Richard L. , Moy James , Lumry William , Grunebaum Eyal , Nemet Agnes , Roifman Chaim M. , Sussman Gordon 
Published: October 2014

Background: IVIG-SN is a modern intravenous immunoglobulin with multiple pathogen elimination steps. This clinical trial in patients with primary immunodeficiency (PID) was designed to evaluate the safety, efficacy, and tolerability of this product in adults and children. Methods: Forty-four patients with PID were treated with IVIG-SN for 12 months. IgG trough levels and pharmacokinetics of IVIG-SN were evaluated as well as efficacy and safety according to standard FDA guidelines. Results: Overall, a total of 572 IVIG-SN infusions were administered according to either a 21- or a 28-day schedule. IgG trough levels during the treatment period ranged from 823.00 to 902.77 mg/dL, respectively, and half-life in serum of the administered IgG was 43.45 ± 30.25 days. There were no deaths and no adverse events leading to withdrawal from the study. Of all infusions administered, only 137 (24%) were temporally associated with an adverse event (AE). The upper bound for the 95% CI for the frequency of infusions temporally associated with an AE was 29.2%. Drug-related AEs were predominantly mild, and there were no acute serious bacterial infections during the study. Efficacy was also demonstrated by low rates of missed work, school, or daycare days (mean 2.6 days); unscheduled visits to physicians (mean 1.7); and therapeutic antibiotic use (mean 15 days). Conclusion: IVIG-SN is effective in preventing infections and is safe and well tolerated. Statement of novelty: This efficacy and toxicity trial was conducted using a new IVIG preparation.
Association Mapping of Disease Resistance Traits in Rainbow Trout Using Restriction Site Associated DNA Sequencing
Authors: Campbell Nathan R , LaPatra Scott E , Overturf Ken , Towner Richard , Narum Shawn R 
Published: October 2014

Abstract
Recent advances in genotyping-by-sequencing have enabled genome-wide association studies in nonmodel species including those in aquaculture programs. As with other aquaculture species, rainbow trout and steelhead (Oncorhynchus mykiss) are susceptible to disease and outbreaks can lead to significant losses. Fish culturists have therefore been pursuing strategies to prevent losses to common pathogens such as Flavobacterium psychrophilum (the etiological agent for bacterial cold water disease [CWD]) and infectious hematopoietic necrosis virus (IHNV) by adjusting feed formulations, vaccine development, and selective breeding. However, discovery of genetic markers linked to disease resistance offers the potential to use marker-assisted selection to increase resistance and reduce outbreaks. For this study we sampled juvenile fish from 40 families from 2-yr classes that either survived or died after controlled exposure to either CWD or IHNV. Restriction site−associated DNA sequencing produced 4661 polymorphic single-nucleotide polymorphism loci after strict filtering. Genotypes from individual survivors and mortalities were then used to test for association between disease resistance and genotype at each locus using the program TASSEL. After we accounted for kinship and stratification of the samples, tests revealed 12 single-nucleotide polymorphism markers that were highly associated with resistance to CWD and 19 markers associated with resistance to IHNV. These markers are candidates for further investigation and are expected to be useful for marker assisted selection in future broodstock selection for various aquaculture programs.
Fire evolution in the radioactive forests of Ukraine and Belarus: future risks for the population and the environment
Authors: Evangeliou N. , Balkanski Y. , Cozic A. , Hao W. M. , Mouillot F. , Thonicke K. , Paugam R. , Zibtsev S. , Mousseau T. A. , Wang R. , Poulter B. , Petkov A. , Yue C. , Cadule P. , Koffi B. , Kaiser J. W. , Møller A. P. 
Published: October 2014

In this paper, we analyze the current and future status of forests in Ukraine and Belarus that were contaminated after the nuclear disaster in 1986. Using several models, together with remote‐sensing data and observations, we studied how climate change in these forests may affect fire regimes. We investigated the possibility of137Cs displacement over Europe by studying previous fire events, and examined three fire scenarios that depended on different emission altitudes of137Cs, assuming that 10% of the forests were affected by fires. Field measurements and modeling simulations confirmed that numerous radioactive contaminants are still present at these sites in extremely large quantities.Forests in Eastern Europe are characterized by large, highly fire‐prone patches that are conducive to the development of extreme crown fires. Since 1986, there has been a positive correlation between extreme fire events and drought in the two contaminated regions. Litter carbon storage in the area has doubled since 1986 due to increased tree mortality and decreased decomposition rates; dead trees and accumulating litter in turn can provide fuel for wildfires that pose a high risk of redistributing radioactivity in future years. Intense fires in 2002, 2008, and 2010 resulted in the displacement of137Cs to the south; the cumulative amount of137Cs re‐deposited over Europe was equivalent to 8% of that deposited following the initial Chernobyl disaster. However, a large amount of137Cs still remains in these forests, which could be remobilized along with a large number of other dangerous, long‐lived, refractory radionuclides. We predict that an expanding flammable area associated with climate change will lead to a high risk of radioactive contamination with characteristic fire peaks in the future. Current fire‐fighting infrastructure in the region is inadequate due to understaffing and lack of funding. Our data yield the first cogent predictions for future fire incidents and provide scientific insights that could inform and spur evidence‐based policy decisions concerning highly contaminated regions around the world, such as those of Chernobyl.
Effects of La–Zn substituent and calcination temperature on the microstructure and magnetic properties of Sr-ferrites
Authors: Li Xiangcheng , Zhao Zhang , Zhu Boquan 
Published: October 2014

Abstract
In this study, La–Zn-substituted SrFe12O19 ferrites were synthesized using the traditional ceramic process. The by-products of iron oxide scales from a steel plant were used as the main raw materials. The influence of the La–Zn substituent and the calcination temperature on the microstructure and magnetic properties of Sr1
−

x
La
x
Fe12
−

x
Zn
x
O19 ferrites was investigated. The results showed that with the increase in the x value, the crystalline lattice constant of the a- and c-axes and the cell volume decreased. There was no α-Fe2O3 phase in the ferrites when the value of x was 0.3. The corresponding saturation magnetization (M
s) and remnant magnetization (M
r) values were, respectively, about 65 emu g−
1 and 39.5 emu g−
1. Both values of M
s and M
r rise to the maximum value. When the calcination temperature was reduced from 1200°C to 1150°C, the average particle size decreased from 0.9 μm to 0.7 μm and M
s remained at 65 emu g−
1. However, the coercivity increased from 2690 Oe to 3100 Oe.
L'impact de la présence d'alcool à l'écran sur le désir de consommer de jeunes Français : effet de la valence et du sexe
Authors: Bréhonnet Rémi , Gallopel-Morvan Karine , Gabriel Patrick 
Published: October 2014

Qu’il s’agisse de placement de produit, de marque ou de présence pour un souci de réalisme, l’impact de la consommation d’alcool dans les productions cinématographiques interroge. Afin d’étendre les travaux qui ont étudié l’effet de certaines caractéristiques du placement d’alcool à l’écran, cette recherche examine, chez de jeunes hommes et femmes, l’impact d’un extrait de film comportant une scène de consommation d’alcool à valence positive (consommation dans un contexte convivial, festif, etc.) ou négative (consommation dans un contexte de dépendance, d’alcoolisme, etc.) sur l’attitude et sur le désir de s’alcooliser. Les résultats montrent que la valence a un effet positif ou négatif sur l’attitude, celle-ci impactant à son tour le désir de consommer. L’analyse montre également que le sexe a une influence sur le désir de consommer : les filles semblent plus influencées par la présence de l’alcool dans les films. Les résultats sont en revanche plus mitigés sur l’attitude. Après avoir discuté les résultats et indiqué les limites de la recherche, les implications en termes de santé publique seront présentées.
La lutte contre les moustiques (Diptera: Culicidae): diversité des approches et application du contrôle biologique
Authors: Bawin T. , Seye F. , Boukraa S. , Zimmer J.-Y. , Delvigne F. , Francis F. 
Published: October 2014

RésuméPlusieurs espèces de moustiques (Diptera: Culicidae) sont des vecteurs de zoonoses d’incidence médicale et vétérinaire considérables. Une modification de la distribution géographique de ces vecteurs majoritairement engendrée par des facteurs anthropiques est actuellement accompagnée de (ré-)émergences de maladies infectieuses en Europe et en Amérique du Nord. Depuis l’avènement des insecticides de synthèse lors de la seconde guerre mondiale, les moustiques font l’objet de recherches de plus en plus étendues et approfondies. Dans une vision de lutte intégrée, les moyens de lutte anti-vectorielle se répartissent aujourd’hui selon quatre axes principaux: (1) la gestion environnementale et le contrôle physique, (2) le contrôle chimique, (3) le contrôle génétique, et (4) le contrôle biologique par le biais d’entomophages et de micro-organismes entomopathogènes. Dans ce contexte, ces derniers ont un potentiel intéressant car ils possèdent la capacité d’infecter et de tuer l’hôte avec une sélectivité plus ou moins prononcée. Cet article se propose de resituer le contrôle biologique parmi les autres techniques dans la lutte anti-vectorielle contre les moustiques, et de faire état des potentialités et des perspectives offertes par les bactéries, virus et champignons entomopathogènes. Leur utilisation sous forme de biopesticides est enfin discutée.
The use of traditional and novel techniques to determine the hardness and indentation properties of immature radicular dentin treated with antibiotic medicaments followed by ethylenediaminetetraacetic acid
Authors: Yassen Ghaeth H. , Al-Angari Sarah S. , Platt Jeffrey A. 
Published: October 2014

ABSTRACT
Objective: The objective was to investigate the effect of intracanal antibiotic medicaments followed by ethylenediaminetetraacetic acid (EDTA) on the indentation properties and hardness of radicular dentin using a BioDent reference point indenter and a traditional microhardness technique, respectively. Materials and Methods: Specimens with intact root canal dentin surfaces and polished radicular dentin specimens were obtained from immature human premolars. Each type of specimen was randomly assigned (n = 10 per group) and treated with either double antibiotic paste (DAP) for 4-week followed by EDTA for 5 min, triple antibiotic paste (TAP) for 4-week followed by EDTA for 5 min, EDTA for 5 min or Hank's balanced salt solution (control). The BioDent reference point indentor and Vickers microhardness tester were used to measure the indentation properties of root canal surfaces and the hardness of polished dentin specimens, respectively. One-way ANOVA followed by Fisher's protected least significant differences were used for statistical analyses. Results: Both types of radicular dentin treated with antibiotic pastes and/or EDTA had a significant increase in the majority of indentation properties and a significant reduction in hardness compared to the untreated dentin. Furthermore, treatment of dentin with antibiotic pastes and EDTA caused significant increases in indentation properties and a significant reduction in hardness compared to EDTA-treated dentin. However, the RPI technique was not able to significantly differentiate between DAP + EDTA and TAP + EDTA-treated dentin. Conclusion: Dentin treated with antibiotic medicaments followed by EDTA had a significant increase the indentation properties and significantly reduction in hardness of radicular dentin.
The effect of surface roughness on ceramics used in dentistry: A review of literature
Authors: Rashid Haroon 
Published: October 2014

ABSTRACTLong term clinical success of modern dental ceramics depends on a number of factors. These factors include the physical properties of the material, the laboratory fabrication process, the laboratory fabrication technique and clinical procedures that may damage these brittle materials. The surface structure and composition of a dental restorative material influences the initial bacterial adhesion, and a rough material surface will accumulate more plaque. Biomaterials for the restoration of oral function are prone to biofilm formation, affecting oral health. An up to date online database search was performed using the keywords “bacterial biofilm,” “ceramic strength,” “dental ceramics” and “surface roughness.” The searches were performed on Medline/PubMed, and Scopus and the cross references were further searched in the databases to verify further studies. The relevant papers included original articles, systemic reviews, case reports and letters to the editor. All the papers were reviewed, and the most relevant studies were selected for referencing by the author. The aim of this paper is to highlight the influence of rougher surfaces on the ceramic strength and plaque accumulation leading to bacterial biofilm formation.
Non-tangential Maximal Function Characterizations of Hardy Spaces Associated with Degenerate Elliptic Operators
Authors: Zhang Junqiang , Cao Jun , Jiang Renjin , Yang Dachun 
Published: October 2014

AbstractLet w be either in the Muckenhoupt class of A2(ℝn) weights or in the class of QC(ℝn) weights, and let be the degenerate elliptic operator on the Euclidean space ℝn, n ≥ 2. In this article, the authors establish the non-tangential maximal function characterization of the Hardy space associated with , and when with , the authors prove that the associated Riesz transform is bounded from to the weighted classical Hardy space .
Fine structure of plasmaspheric hiss
Authors: Summers Danny , Omura Yoshiharu , Nakamura Satoko , Kletzing Craig A. 
Published: October 2014

AbstractPlasmaspheric hiss has been widely regarded as a broadband, structureless, incoherent emission. In this study, by examining burst‐mode vector waveform data from the Electric and Magnetic Field Instrument Suite and Integrated Science instrument on the Van Allen Probes mission, we show that plasmaspheric hiss is a coherent emission with complex fine structure. Specifically, plasmaspheric hiss appears as discrete rising tone and falling tone elements. Our study comprises the analysis of two 1 h samples within which a total of eight 1 s samples were analyzed. By means of waveform analysis on two samples, we identify typical amplitudes, phase profiles, and sweep rates of the rising and falling tone elements. The exciting new observations reported here can be expected to fuel a reexamination of the properties of plasmaspheric hiss, including a further reanalysis of the generation mechanism for hiss.