bluuebunny/crossref_metadata_2025 huggingface dataset:
Double‐nozzle air‐jet electrospinning for nanofiber fabrication
Authors: Pu Congcong , He Jianxin , Cui Shizhong , Gao Weidong
Published: October 2013

A novel double‐nozzle air‐jet electrospinning apparatus was developed to fabricate nanofibers on a large scale. The distribution of the electric field at different nozzle distances was simulated to analyze the jet path, productivity, and deposition area of nanofiber webs and the nanofiber morphology. Our experiments showed that the bubbles usually ruptured intermittently on the top surface of the two nozzles and the jets traveled in a straight path with a high initial velocity. A continuous and even thickness of the nanofiber webs were obtained when the nozzle distances was less than 55 mm. At nozzle distances of 55 mm, the received fibers were thin with the lowest standard deviation. Experimental parameters involving the applied voltage, collecting distance, and air flow rate were also investigated to analyze the nanofiber morphology at a nozzle distance of 55 mm. The results show that the nanofibers presented a finer and thinner diameter at an applied voltage of 36 kV, a collecting distance of 18 cm, and an air flow rate of 800 mL/min. The nanofiber production of this setup increased to nearly 70 times that with a single‐needle electrospinning setup. On the basis of the principle of this air‐jet electrospinning setup, various arrangements of multinozzle electrospinning setups could be designed for higher throughput of nanofibers. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 40040.
Fluorinated polybenzimidazopyrrolones with excellent alkaline‐hydrolysis resistance
Authors: Tao Liming , Yang Haixia , Liu Jingang , Fan Lin , Yang Shiyong
Published: October 2013

Two novel aromatic tetraamines containing bulky lateral phenyl unit and multiple trifluoromethyl groups, 1,1‐bis[4‐(3′,4′‐diaminophenoxy)phenyl]‐1‐(3″‐trifluoromethylphenyl)−2,2,2‐trifluoroethane (6FTA) and 1,1‐bis[4‐(3′,4′‐diaminophenoxy)phenyl]‐1‐[3″,5″‐bis(trifluoromethyl)phenyl]‐2,2,2‐trifluoroethane (9FTA) were synthesized and characterized. A series of fluorinated aromatic polybenzimidazopyrrolones (polypyrrolones, PPys) were synthesized via a two‐step polycondensation procedure. The inherent viscosities of the precursors, poly(amide amino acid) (PAAA), ranged from 0.39 dL/g to 0.54 dL/g. All the FPPys were amorphous. The freestanding FPPy films could be prepared, which exhibited good thermal stability with the glass transition temperature of 315–389°C, the temperatures of 5% weight loss (T5%) of 497–535°C in nitrogen and residual weight retention at 700°C over 60%. All the FPPy films exhibited excellent alkaline‐hydrolysis resistance which retained their original shapes and toughness after boiling 7 days in 10% sodium hydroxide solution. Also after boiling 8 h in 10% sodium hydroxide solution, the tensile strength could retain as high as 56% of the original values. The alkaline‐hydrolysis resistance was much better than the polyimides which had similar chemical structures. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 40041.
Structural Changes and Antibody Enrichment in the Lungs Are Early Features of Anti–Citrullinated Protein Antibody–Positive Rheumatoid Arthritis
Authors: Reynisdottir Gudrun , Karimi Reza , Joshua Vijay , Olsen Helga , Hensvold Aase Haj , Harju Anders , Engström Marianne , Grunewald Johan , Nyren Sven , Eklund Anders , Klareskog Lars , Sköld Carl Magnus , Irinel Catrina Anca
Published: October 2013

Objective

It has been suggested that immunologic events in the lungs may be involved in triggering immunity, in particular production of anti–citrullinated protein antibodies (ACPAs) during early phases of rheumatoid arthritis (RA). The aim of this study was to investigate the structural and immunologic features of the lungs in incident cases of early RA in relation to ACPA presence and smoking status.

Methods

High‐resolution computed tomography (HRCT) was used to examine the lungs of 105 patients with early, untreated RA (70 with ACPA‐positive RA and 35 with ACPA‐negative RA) and 43 healthy individuals. Bronchoscopy with collection of bronchoalveolar lavage (BAL) fluid and mucosal bronchial biopsy specimens was performed in 23 RA patients. The presence of citrullinated proteins in the bronchial tissue was detected by immunohistochemical staining. ACPAs (detected with an anti–cyclic citrullinated peptide 2 test) and total Ig levels were determined in the sera and BAL fluid of RA patients.

Results

HRCT imaging revealed that 63% of ACPA‐positive RA patients had parenchymal lung abnormalities, compared with only 37% of ACPA‐negative RA patients and 30% of healthy controls (each P < 0.05). These significant differences remained after adjustment for smoking status. Airway changes detected by HRCT were more frequent in RA patients than in healthy controls (66% versus 42%; P < 0.05), but there was no difference between ACPA‐positive and ACPA‐negative RA patients. Immunohistochemical studies of the bronchial tissue showed increased staining for citrullinated proteins in ACPA‐positive RA patients compared with ACPA‐negative RA patients (P < 0.05). ACPA levels were relatively higher in the BAL fluid as compared with the sera of ACPA‐positive RA patients, suggesting that there is local production of ACPAs in the lungs of these patients.

Conclusion

The presence of ACPAs is associated with parenchymal lung abnormalities, site‐specific citrullination, and antibody enrichment in the lungs early in the development of ACPA‐positive RA.
Increased Surgeon Experience With Rheumatoid Arthritis Reduces the Risk of Complications Following Total Joint Arthroplasty
Authors: Ravi Bheeshma , Croxford Ruth , Austin Peter C. , Hollands Simon , Paterson J. Michael , Bogoch Earl , Kreder Hans , Hawker Gillian A.
Published: October 2013

Objective

To determine the relationship between surgeon experience with, and complications following, total joint arthroplasty (TJA) in patients with rheumatoid arthritis (RA).

Methods

Using administrative data, we assembled a cohort of patients with RA who had undergone at least 1 elective primary hip or knee replacement procedure between 2002 and 2009. Cox proportional hazards, censored on death and accounting for clustering of patients within surgeons, were used to determine the relationship between overall and “RA‐specific” surgeon TJA volume and the occurrence of a composite “complication” outcome (revision, infection, dislocation, or periprosthetic fracture within 2 years of the initial TJA), controlling for potential confounders (patient age, sex, comorbidity, and disease severity).

Results

We identified 4,762 patients with RA who were eligible for TJAs (1,515 total hip arthroplasties and 3,247 total knee arthroplasties). Among these patients, 152 (3.2%) experienced a surgical complication within 2 years of the procedure. After controlling for patient and hospital factors, greater surgeon TJA volume in patients with RA (RA TJA), but not overall TJA volume (all TJA), was associated with a reduced risk of complications (for surgeon RA TJA volume per 10 cases, adjusted hazard ratio [HR] 0.81, 95% confidence interval [95% CI] 0.71–0.93, P = 0.002; for surgeon all TJA volume, adjusted HR 0.98, 95% CI 0.97–1.00, P = 0.09).

Conclusion

In a cohort of patients with RA who underwent hip or knee TJA, increased surgeon experience performing TJA in patients with RA, irrespective of their overall TJA experience and hospital factors, was associated with a decreased risk of surgical complications. These findings have potential implications for surgeon training and the referral practices of rheumatologists.
Anatomist and the pioneer of radiology Étienne destot—95th anniversary of his death
Authors: Báča Václav , Kachlík David , Báčová Tereza , Bartoška Radek , Marvan Jiří , Douša Pavel , Secrest Thomas , Džupa Valér
Published: October 2013

Destot was a leading pioneer in radiology, a pupil of Ollier, an anatomist, and researcher who followed in the experimental medicine tradition of Claude Bérnard. This work is an extensive, in depth, look at the life and work of Étienne Destot. On February 5, 1896, he began performing X‐ray examinations, less than two months after Roentgen's discovery! His pioneering work described a space bordered by the hamate, capitate, triquetrum, and lunate; this space is now known as Destot's space. Tanton stated that Destot was the first to reveal the mechanism of fractures of the posterior margin of the distal tibia and to emphasize their clinical relevance; in honor of this contribution, Tanton named such a fracture the “fracture of Destot.” Moreover, Destot is credited with being the first physician to use the term “pilon” in the orthopedic literature. He first described fractures of the scaphoid in 1905. He also described superficial hematomas, Destot's sign, located above the inguinal ligament or in the scrotum or thigh. Such hematomas are indicative of pelvic fractures. Destot is credited with inventing or improving many pieces of medical equipment (e.g., Lambotte's screw plates, anastomotic boutons for the digestive tube, monopolar endocavital radiological tubes). He was also active in developing technical aspects of equipment (e.g., radioscopic examination of the heart, a prototype of the mobile radiological laboratory). Étienne Destot is best known as a radiologist; however, his influence extends well beyond this field. He was an anatomist and surgeon, the founder of radiology in Lyon, prosector, physician, electrician, researcher, and artist. Clin. Anat. 27:282–285, 2014. © 2013 Wiley Periodicals, Inc.
Transpedal access after failed anterograde recanalization of complex below‐the‐knee and femoropoliteal occlusions in critical limb ischemia
Authors: Ruzsa Zoltán , Nemes Balázs , Bánsághi Zoltán , Tóth Károly , Kuti Ferenc , Kudrnova Slavka , Berta Balázs , Hüttl Kálmán , Merkely Béla
Published: October 2013

Background

Successful angioplasty is one of the main factor of limb salvage during critical limb ischemia. In complex femoropopliteal to infrapopliteal occlusions, an anterograde recanalization attempt can fail in up to 20% of the cases. The purpose of this dual center pilot study was to evaluate the acute success and clinical impact of retrograde transpedal access for retrograde below‐the‐knee and femoropopliteal chronic total occlusions after failed anterograde attempt and to access the late complications at the puncture site.

Methods

The clinical and angiographic data of 51 consecutive patients with CLI treated by retrograde transpedal recanalization between 2010 and 2011 were evaluated in a pilot study. We have examined the 2‐month and 1 year major adverse events (MAEs) and clinical success. In all cases after failure of the anterograde recanalization of occluded below‐the‐knee segments due to unsuccessful penetration or failed re‐entry, the anterior tibial or posterior tibial artery was punctured under fluoroscopic guidance and retrograde recanalization was performed. Direct revascularization was tried firstly following the angiographic zones, but in failed cases indirect revascularization was carried out with increasing the collateral flow to the wound.

Results

Successful direct retrograde revascularization was achieved successfully in 40 patients (78.4%) and indirect revascularization was done in 10 patients (19.6%). Revascularization was failed in one patient (2%). MAE at 2 and 12 months follow‐up was 6 (11.7%) and 11 (24%). Limb salvage at 2 and 12 months was 93% and 82.3%, respectively. Balloon angioplasty was performed in all interventions and provisional stenting was done in 34 patients (66.7%). One major and three minor vascular complications occurred after the procedure. The mean basal and control creatinine level was 120.9 ± 133.4 and 123.8 ± 131.3 μmol/L (P = 0.83) after the procedure.

Conclusion

Failed antegrade attempts to recanalize CTO‐s of femoropopliteal and infrapopliteal vessels can be salvaged using a retrograde transpedal access, with a low acute and late complication rate. This technique could be valuable for patients with critical limb ischemia due to femoropopliteal and infrapopliteal occlusions. © 2013 Wiley Periodicals, Inc.
Robust Heterogeneous Nickel Catalysts with Tailored Porosity for the Selective Hydrogenolysis of Aryl Ethers
Authors: Zaheer Muhammad , Hermannsdörfer Justus , Kretschmer Winfried P. , Motz Günter , Kempe Rhett
Published: October 2013

SiC materials with tailored porosity and integrated Ni NPs (Ni@SiC) were synthesized via microphase separation of polycarbosilane‐block‐polyethylene followed by its pyrolysis. Changing the length of organic block allowed the synthesis of micro, meso and hierarchical Ni@SiC materials which were characterized by PXRD, TEM, TGA, and nitrogen physisorption. Selective hydrogenolysis of aryl ethers mimicking the most abundant linkages of lignin was achieved in water avoiding the possible hydrogenation of aromatic rings.
Diagnostic Analyses and Applications of the Moisture Helicity and the Thermal Helicity for Two Strong “Sauna” Weather Processes in Northern China
Authors: Shuai YANG , Bin CHEN , Shou‐Ting GAO
Published: October 2013

“Sauna” weathers generally occur in high‐temperature environments during summertime. However, it is difficult to diagnose sultry “sauna” weather only based on the single temperature parameter because of its large humidity. Previous studies show that the relatively stable subtropic‐high circulation dominates the middle troposphere and weak sinking motion maintains during “sauna” weather events. Due to its special hot and humid environment and circulation conditions, it is of particular importance to find a simple and convenient parameter to characterize high‐temperature and high‐humidity “sauna” weather. Based on previous research, the IM (Ingredients‐based methodology) method, which is developed for rainfall studies in the past, is extended to the study of “sauna” weather in this paper. Several physical variables such as high temperature, large relative humidity, and sinking motion, which are used as single factors to describe “sauna” weather in the past studies, are combined into IM theory to diagnose “sauna” weather. In terms of the IM method, thermal helicity (TH), moisture helicity (MH), and the moist thermal helicity (MTH), are introduced to dynamically identify “sauna” weather. Two “sauna” weather events in North China are selected to calculate above several parameters. One is from 30 July to 4 August 2002. Another is from 7 to 9 July 2009. And the generalized moist potential vorticity (GMPV) is used to make a comparison with them. It is found that the MH anomalies accompany the “sauna” weather processes, concentrate in the lower troposphere around Beijing and its peripheral areas in North China. However, the coverage of TH anomalies is larger than our target region of the “sauna” weather events. Even for the MTH and GMPV including both temperature and humidity effects, it is also worse to use their anomalies areas to dynamically identify “sauna” weather than using MH's anomalies. It implies that humidity is a determining factor during the sultry “sauna” weather process in North China in general high‐temperature summertime. The MH, which integrates both the atmospheric circulation characteristics and humidity effect, is a possible optimization factor to dynamically identify “sauna” weather in North China. And it has great value of practical application to analysis of “sauna” weather.
Theory and Numerical Modeling of Under‐Dense Heating With Powerful X‐Mode Pump Waves
Authors: Shu‐Ji HAO , Ju‐Tao YANG , Hai‐Qin CHE , Qing‐Liang LI , Zhen‐Sen WU
Published: October 2013

Based on the mechanisms of both electron cooling and heating in the ionosphere, a theoretical simulation model of under‐dense heating by X‐mode waves is constructed. And this model is verified by simulating the known experimental results. Using this model, we analyze the influences of heating parameters and the ambient ionosphere on the heating effects. The results show that in the under‐dense heating ionosphere by powerful X‐mode wave, the heating effects are enhanced when the effective radiated power (ERP) increases, and weakened as the heating frequency increases. The lower the electron temperature and the smaller the density, the stronger the heating effects are. Finally, some applications of under‐dense heating by X‐mode waves are analyzed.
The Diurnal Variation of Geo‐Electric Field Along the Longitude and Latitude Chains in China Mainland
Authors: Teng‐Fa CUI , Xue‐Bin DU , Qing YE , Jun‐Ying CHEN , Jian‐Jun WANG , Zhang‐Hui AN , Ying‐Ying FAN , Jun LIU
Published: October 2013

This paper studied the time and frequency characteristics of the geo‐electric field diurnal variation along two longitude chains and two latitude chains in China mainland, using the data of geo‐electric field observed at 37 stations along the chains. The following significant results are obtained. The diurnal variation at most stations appears as semi‐diurnal waves twice a day, near before and after the noon; in descending order of the FFT amplitude spectrums, the main periods of the diurnal variation are 12.4 h/12 h, 8 h, 24 h, etc., which are in accordance with the periods of the tidal harmonic components; the diurnal variation changes with latitude as the wave crest‐to‐trough amplitude gradually becomes bigger/smaller with reduced/increased latitude of the station, and also varies with longitude as the phase difference agrees with the local‐time difference between the stations along the same latitude. Furthermore, the amplitude of the diurnal variation is related with the Loyd season, which reduces orderly in J‐, E‐ and D‐seasons. The possible reasons which cause the main periodic components of the diurnal variation have been discussed, as a result, it is believed that the variation of the ground eddy current intensity caused by lunisolar tidal forces and the space electromagnetic activity aroused by the solar wind jointly produce the semi‐diurnal period components of the geo‐electric diurnal variation.
An Optimal Model of the Equivalent Source for Reduction‐to‐Plane of Potential Field Data on Uneven Surface and the New Method to Deduce Its Unit Potential Field Expression
Authors: Yu‐Lin AN , Yu‐Pu CHAI , Ming‐Hua ZHANG , Jin‐Ming HUANG , Ji‐Hua QIAO
Published: October 2013

On the basis of paper of Hanson and Miyazaki, this work defines the optimal model of the equivalent source for reduction‐to‐plane of potential field data on uneven surface, and uses this model to develop a program which can carry out the reduction‐to‐plane of potential field data of a large area at high precision and high speed. In the process of deducing the unit potential field expression of the optimal model, we propose a model transposition method based on the mapping relationship between models and their potential field expressions. A quite brief expression of the unit potential field can be deduced easily by using the model transposition method. We consider that this model transposition method may have some catholicity in deducing potential expressions, and suggest readers who work with potential field theory and method research pay attention to it, so as to consult and use this method to solve similar problems in practice, and develop and perfect this approach.
Well Log Anomalies Caused by Gas Hydrate Dissociation in the Shenhu Area, Northern South China Sea
Authors: Xiu‐Juan WANG , Shi‐Guo WU , Ji‐Liang WANG , Sheng‐Xiong YANG , Zhen‐Zhen WANG
Published: October 2013

The drilling GMGS‐1 reveals that gas hydrates are present above a stable zone with a thickness of 10 m at site SH3 in the Shenhu area, northern South China Sea. At this place, the gas hydrate saturation estimated from observed pore‐water chloride values is up to 26% in the pore space. Higher resistivity, lower P‐wave velocity and slightly increasing density characterize the gas hydrate‐bearing sediments. To analyze this low P‐wave velocity, the simplified three‐phase Biot‐type equation (STPBE) is used to calculate the water‐saturated P‐wave velocity. The results show that at the depth of 195 m, the P‐wave velocity from wireline logging is lower than that of the water‐saturated velocity of the normal sediments. The Archie's parameters used to calculate gas hydrate saturation from resistivity were defined from the cross plot between density porosity and formation factor. Gas hydrate saturation estimated from resistivity using the Archie equation with a=1.1 and m=2.3 is about 5%∼20% of the pore space, with a maximum value 26.8%, which shows that the distribution of gas hydrates is inhomogeneous in vertical direction. The dissociation of gas hydrates (the mixture of free gas and water) may be caused by drilling. Either the in‐situ free gas or gas released from gas hydrate dissociation can cause the low well‐log P‐wave velocity. Due to surface seismic data were acquired before drilling, synthetic seismograms generated using different P‐wave velocities are compared with the real seismic data, which can be used to identify the cause of the low P‐wave velocity observed in the well log.
Metal Concentrations in Plants from Mining Areas in South Morocco: Health Risks Assessment of Consumption of Edible and Aromatic Plants
Authors: El Hamiani Ouafae , El Khalil Hicham , Sirguey Catherine , Ouhammou Ahmed , Bitton Gabriel , Schwartz Christophe , Boularbah Ali
Published: October 2013

The metals uptake by plants crops grown on garden soils surrounding three mining areas in South Morocco and the assessment of the potential health risk associated with human consumption of edible crops collected were investigated. Results indicated that high metal concentration of Co, Cr, Cu, Mn, and Ni in aerial parts of the aromatic plants and vegetables from mines A and B exceed the usual values reported in literature. The values of daily intake of metals (DIM) lower than oral reference dose (RfD) and health risk index <1, indicating that the consumption of edible and aromatic plants grown in garden soils is relatively free of risks. However, consumption of the plants from mine A represents an average of 1% of RfD for Mn. This value is relatively important and remains high as compared to contribution of other food sources. The prevention of environmental risks associated with gardening in urban and industrial areas is necessary and essential to propose recommendations both to gardeners and to decision‐makers.
Involvement and targeted intervention of dysregulated Hedgehog signaling in osteosarcoma
Authors: Lo Winnie W. , Wunder Jay S. , Dickson Brendan C. , Campbell Veronica , McGovern Karen , Alman Benjamin A. , Andrulis Irene L.
Published: October 2013

BACKGROUND

During development, the Hedgehog pathway plays important roles regulating the proliferation and differentiation of chondrocytes, providing a template for growing bone. In this study, the authors investigated the components of dysregulated Hedgehog signaling as potential therapeutic targets for osteosarcoma.

METHODS

Small‐molecule agonists and antagonists that modulate the Hedgehog pathway at different levels were used to investigate the mechanisms of dysregulation and the efficacy of Hedgehog blockade in osteosarcoma cell lines. The inhibitory effect of a small‐molecule Smoothened (SMO) antagonist, IPI‐926 (saridegib), also was examined in patient‐derived xenograft models.

RESULTS

An inverse correlation was identified in osteosarcoma cell lines between endogenous glioma‐associated oncogene 2 (GLI2) levels and Hedgehog pathway induction levels. Cells with high levels of GLI2 were sensitive to GLI inhibition, but not SMO inhibition, suggesting that GLI2 overexpression may be a mechanism of ligand‐independent activation. In contrast, cells that expressed high levels of the Hedgehog ligand gene Indian hedgehog (IHH) and the target genes patched 1 (PTCH1) and GLI1 were sensitive to modulation of both SMO and GLI, suggesting ligand‐dependent activation. In 2 xenograft models, active autocrine and paracrine, ligand‐dependent Hedgehog signaling was identified. IPI‐926 inhibited the Hedgehog signaling interactions between the tumor and the stroma and demonstrated antitumor efficacy in 1 of 2 ligand‐dependent models.

CONCLUSIONS

The current results indicate that both ligand‐dependent and ligand‐independent Hedgehog dysregulation may be involved in osteosarcoma. It is the first report to demonstrate Hedgehog signaling crosstalk between the tumor and the stroma in osteosarcoma. The inhibitory effect of IPI‐926 warrants additional research and raises the possibility of using Hedgehog pathway inhibitors as targeted therapeutics to improve treatment for osteosarcoma. Cancer 2014;120:537–547. © 2013 American Cancer Society.
Point of Care Testing in Cardiac Surgery: Diagnostic Modalities to Assess Coagulation and Platelet Function
Authors: Stafford Marshall , Weitzel Nathaen
Published: October 2013

Preclinical Research

Point of Care testing in the perioperative arena is a high priority topic, specifically in cardiac surgery where a majority of perioperative blood transfusions occur. Platelet function in particular is of interest in cardiac surgery as cardiopulmonary bypass itself creates known platelet dysfunction, but also because more and more patients are on antiplatelet agents due to coronary stenting procedures. This review will focus on presenting current data relating to platelet function in the perioperative setting, along with a brief review of general coagulation concepts.
Potential Contribution of Pleiotropic Effects of Direct Anticoagulants to Clinical Benefits
Authors: Schneider David J.
Published: October 2013

Clinical Development Phases I‐III Regulatory, Quality, Manufacturing

Two recent large clinical trials that enrolled exclusively or predominantly patients with ST elevation myocardial infarction and tested direct acting anticoagulants (bivalirudin, rivaroxaban) demonstrated a reduction in mortality. While the anticoagulant properties of these agents likely contributed to the beneficial effects, this Commentary will focus on the nonanticoagulant effects and will consider the premise that pleiotropic effects may have contributed to the observed benefit. In these trials, hearts experienced ischemia/reperfusion and the myocardium was directly exposed to activated coagulation factors. Activation of proteinase‐activated receptors (PARs) by thrombin and factor Xa would be predicted to increase inflammation and promote ventricular dilatation and fibrosis. Because direct acting anticoagulants effectively inhibit both free and clot‐bound coagulation factors, the extent of exposure to activated coagulation factors would be expected to be reduced. The anticipated preservation of left ventricular function should contribute to a reduction in the subsequent risk of death.
Novel Therapeutics for Thromboprophylaxis in Nonvalvular Atrial Fibrillation
Authors: Gazi Emine , Temiz Ahmet , Barutcu Ahmet , Colkesen Yucel
Published: October 2013

Clinical Development Phases I‐III Regulatory, Quality, Manufacturing

Atrial fibrillation (AF) is both a health and a social problem. AF is related to the elevated risk of thromboembolic events with stroke being the most important. It adversely affects life expectancy and quality. The risk of ischemic stroke is increased fivefold in patients with AF. Therapeutic options for lowering the risk of stroke in patients with AF consist of vitamin K antagonists and antiplatelet agents, which have relative risk reductions of approximately 60% and 20%, respectively. Alternative therapeutic options available to reduce the risk of stroke in patients with nonvalvular AF are relatively new. In recent years, new oral anticoagulants have been introduced for this indication. Reversible direct thrombin inhibitors and factor Xa inhibitors are new oral anticoagulant agents that have demonstrated efficacy and good safety profiles for preventing stroke and embolic events. The intent of this overview is to review the novel oral anticoagulants recommended for stroke prevention in patients with AF.
Early adversity, RSA, and inhibitory control: Evidence of children's neurobiological sensitivity to social context
Authors: Skowron Elizabeth A. , Cipriano‐Essel Elizabeth , Gatzke‐Kopp Lisa M. , Teti Douglas M. , Ammerman Robert T.
Published: October 2013

This study examined parasympathetic physiology as a moderator of the effects of early adversity (i.e., child abuse and neglect) on children's inhibitory control. Children's respiratory sinus arrhythmia (RSA) was assessed during a resting baseline, two joint challenge tasks with mother, and an individual frustration task. RSA assessed during each of the joint parent–child challenge tasks moderated the effects of child maltreatment (CM) status on children's independently‐assessed inhibitory control. No moderation effect was found for RSA assessed at baseline or in the child‐alone challenge task. Among CM‐exposed children, lower RSA levels during the joint task predicted the lowest inhibitory control, whereas higher joint task RSA was linked to higher inhibitory control scores that were indistinguishable from those of non‐CM children. Results are discussed with regard to the importance of considering context specificity (i.e., individual and caregiver contexts) in how biomarkers inform our understanding of individual differences in vulnerability among at‐risk children. © 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 964–978, 2014.
Synergistic Recognition of Halide Anions and Saccharides by Oligohydrazide Foldamers
Authors: Bie Fusheng , Wang Ying , Shang Jie , Gallagher Nolan M. , Jiang Hua
Published: October 2013

We synthesized and characterized a new kind of hydrazide oligomer that contains two different types of binding moieties for halide anions and saccharides. The addition of either halide anions or saccharides can induce the oligomers to adopt folded conformations. More interestingly, the oligomers are able to complex both chloride anions and saccharides in the cavity at the same time, implying a synergistic molecular recognition.
CCR2+ monocytes infiltrate atrophic lesions in age‐related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice
Authors: Sennlaub Florian , Auvynet Constance , Calippe Bertrand , Lavalette Sophie , Poupel Lucie , Hu Shulong J. , Dominguez Elisa , Camelo Serge , Levy Olivier , Guyon Elodie , Saederup Noah , Charo Israel F. , Rooijen Nico Van , Nandrot Emeline , Bourges Jean‐Louis , Behar‐Cohen Francine , Sahel José‐Alain , Guillonneau Xavier , Raoul William , Combadiere Christophe
Published: October 2013

Atrophic age‐related macular degeneration (AMD) is associated with the subretinal accumulation of mononuclear phagocytes (MPs). Their role in promoting or inhibiting retinal degeneration is unknown. We here show that atrophic AMD is associated with increased intraocular CCL2 levels and subretinal CCR2+ inflammatory monocyte infiltration in patients. Using age‐ and light‐induced subretinal inflammation and photoreceptor degeneration in Cx3cr1 knockout mice, we show that subretinal Cx3cr1 deficient MPs overexpress CCL2 and that both the genetic deletion of CCL2 or CCR2 and the pharmacological inhibition of CCR2 prevent inflammatory monocyte recruitment, MP accumulation and photoreceptor degeneration in vivo. Our study shows that contrary to CCR2 and CCL2, CX3CR1 is constitutively expressed in the retina where it represses the expression of CCL2 and the recruitment of neurotoxic inflammatory CCR2+ monocytes. CCL2/CCR2 inhibition might represent a powerful tool for controlling inflammation and neurodegeneration in AMD.
Metal leaching, acidity, and altitude confine benthic macroinvertebrate community composition in Andean streams
Authors: Loayza-Muro Raúl A. , Duivenvoorden Joost F. , Kraak Michiel H.S. , Admiraal Wim
Published: October 2013

Andean streams drain metal-rich bedrock and are subjected to an extreme altitude gradient, which may create highly selective conditions for life. The aim of the present study was to evaluate the combined effects of metals and altitude on benthic macroinvertebrate community composition in Andean streams. Metal-rich sites were characterized by high metal concentrations and low pH, and high-altitude sites were characterized by high ultraviolet-B radiation and low concentrations of dissolved organic matter. Canonical correspondence analysis indicated that the patterns in faunal composition were best explained by metals followed by altitude, with dipterans and collembolans occurring mostly under harsh conditions of high altitude and high metal levels. Interaction between metals and altitude was most evident at metal-rich sites. It is suggested that in Andean streams, metal leaching from igneous rock and altitude may be important factors confining benthic macroinvertebrate communities, reducing their numbers and changing their composition toward specialized taxa. Environ Toxicol Chem 2014;33:404–411. © 2013 SETAC
Storage compliance in coupled CO2‐EOR and storage
Authors: Ettehad Amin
Published: October 2013

CO2 storage compliance refers to the safe and consistent storage of a captured anthropogenic CO2 slug in an underground geological structure. This paper investigates the storage compliance in coupled CO2 enhanced oil recovery (EOR) and storage projects. Storage compliance requires an oilfield operator to maintain sufficient CO2 injection and storage capacities throughout an industrial‐scale CO2 capture and EOR‐storage operation. We investigate the uncertainty in two operational parameters that may raise a compliance consideration: annual captured CO2 from the power plant and CO2 injection loss in the oilfield. The objective is to maintain sufficient CO2 injection and storage capacities and maximize the economic benefits from the EOR‐storage operation. We formulate and optimize the storage compliance problem using the method of optimization with Monte Carlo simulation. The results show that appropriate adjustment of the water‐alternating‐gas (WAG) ratio increases both the compliance and the economic benefits. Also, a CO2 storage back‐up in a saline aquifer allows the oilfield operator to implement more profitable EOR‐storage designs. A risk‐seeking operator may practice the saline aquifer back‐up option to simultaneously maximize the benefits and mitigate the risk of storage capacity shortage. Finally, EOR‐storage operation is less efficient than aquifer storage in terms of storage efficiency, and considerably more profitable in terms of tangible economic benefits.
PAYMENTS, PROMOTION, AND THE PURPLE PILL
Authors: Ridley David B.
Published: October 2013

Understanding competition in the US drug market requires knowing how sensitive demand is to prices. The relevant prices for insured consumers are copayments. There are many studies of copayment elasticity in the health literature, but they are of limited applicability for studies of competition. Because of a paucity of data, such studies typically control for neither competitor copayment nor advertising. Whereas previous studies examined copayment sensitivity when copayments for branded drugs move in unison, this study examines copayment sensitivity when copayments diverge. This study uses unique panel data of insurance copayments and utilization for 77 insurance groups, as well as data on advertising. The results indicate that demand can be much more sensitive to copayment than previously recognized. Manufacturers selling drugs with higher copayments than branded competitors can lose substantial market share. Manufacturers can offset the loss of demand by increasing advertising to physicians, but it is costly. Copyright © 2013 John Wiley & Sons, Ltd.
The ABCs of viral hepatitis that define biomarker signatures of acute viral hepatitis
Authors: Duffy Darragh , Mamdouh Rasha , Laird Melissa , Soneson Charlotte , Le Fouler Lenaig , El-Daly Maï , Casrouge Armanda , Decalf Jérémie , Abbas Amal , Eldin Noha Sharaf , Fontes Magnus , Abdel-Hamid Mohamed , Mohamed Mostafa K. , Rafik Mona , Fontanet Arnaud , Albert Matthew L.
Published: October 2013

Viral hepatitis is the leading cause of liver disease worldwide and can be caused by several agents, including hepatitis A (HAV), B (HBV), and C (HCV) virus. We employed multiplexed protein immune assays to identify biomarker signatures of viral hepatitis in order to define unique and common responses for three different acute viral infections of the liver. We performed multianalyte profiling, measuring the concentrations of 182 serum proteins obtained from acute HAV- (18), HBV- (18), and HCV-infected (28) individuals, recruited as part of a hospital-based surveillance program in Cairo, Egypt. Virus-specific biomarker signatures were identified and validation was performed using a unique patient population. A core signature of 46 plasma proteins was commonly modulated in all three infections, as compared to healthy controls. Principle component analysis (PCA) revealed a host response based upon 34 proteins, which could distinguish HCV patients from HAV- and HBV-infected individuals or healthy controls. When HAV and HBV groups were compared directly, 34 differentially expressed serum proteins allowed the separation of these two patient groups. A validation study was performed on an additional 111 patients, confirming the relevance of our initial findings, and defining the 17 analytes that reproducibly segregated the patient populations. Conclusions: This combined discovery and biomarker validation approach revealed a previously unrecognized virus-specific induction of host proteins. The identification of hepatitis virus specific signatures provides a foundation for functional studies and the identification of potential correlates of viral clearance. (HEPATOLOGY 2014;59:1273-1282)
Oxidized alginate hydrogels as niche environments for corneal epithelial cells
Authors: Wright Bernice , De Bank Paul A. , Luetchford Kim A. , Acosta Fernando R. , Connon Che J.
Published: October 2013

Chemical and biochemical modification of hydrogels is one strategy to create physiological constructs that maintain cell function. The aim of this study was to apply oxidised alginate hydrogels as a basis for development of a biomimetic niche for limbal epithelial stem cells that may be applied to treating corneal dysfunction. The stem phenotype of bovine limbal epithelial cells (LEC) and the viability of corneal epithelial cells (CEC) were examined in oxidised alginate gels containing collagen IV over a 3‐day culture period. Oxidation increased cell viability (P ≤ 0.05) and this improved further with addition of collagen IV (P ≤ 0.01). Oxidised gels presented larger internal pores (diameter: 0.2–0.8 µm) than unmodified gels (pore diameter: 0.05–0.1 µm) and were significantly less stiff (P ≤ 0.001), indicating that an increase in pore size and a decrease in stiffness contributed to improved cell viability. The diffusion of collagen IV from oxidised alginate gels was similar to that of unmodified gels suggesting that oxidation may not affect the retention of extracellular matrix proteins in alginate gels. These data demonstrate that oxidised alginate gels containing corneal extracellular matrix proteins can influence corneal epithelial cell function in a manner that may impact beneficially on corneal wound healing therapy. © 2013 The Authors. Journal of Biomedical Materials Research Part A Published byWiley Periodicals, Inc. Part A: 102A: 3393–3400, 2014.
Continuous lipase esterification using process intensification technologies
Authors: Elgue Sébastien , Conté Annelyse , Marty Alain , Condoret Jean‐Stéphane
Published: October 2013

BACKGROUND

Nowadays, developing continuous enzymatic processes, especially when a two‐phase medium is required, remains a great challenge. So, there is a need to provide a technical solution for generating highly controlled interfacial area in a small volume. In this study, four types of reactors conventionally used for chemical process intensification and marketed by Corning, Chart Industries, NiTech Solutions and AM Technology, were tested for continuous lipase‐catalysed esterification in two‐phase medium.

RESULTS

The NiTech oscillating reactor proved to be the more efficient to transform the input mechanical power into mass transfer performance while proposing easily adjustable residence time. Nevertheless, Corning and Chart heat‐exchanger reactors were shown to be very suitable candidates even if mass transfer performances depend on the flow‐rate and therefore are not uncoupled from the residence time. This results in a less convenient choice of operating conditions. The Coflore system was not so convincing but it may be due to the injection device not well adapted to this system.

CONCLUSION

This work demonstrates that novel technologies, recently proposed for intensification of chemical processes, are indeed very suitable and provide a relevant alternative to conventional processes for enzymatic reactions and therefore for two‐phase reactions limited by the interfacial area value. Also, it has been shown here that the model reaction considered could be a simple way to characterize mass transfer performances of these technologies. © 2013 Society of Chemical Industry
Assessing the detection of human papillomavirus late mRNA in liquid base cytology samples for risk stratification of cervical disease
Authors: Chambers George , Millan David , Cuschieri Kate , Cubie Heather A. , Graham Sheila V.
Published: October 2013

Molecular human papillomavirus (HPV) testing is an important and developing tool for cervical disease management. However there is a requirement to develop new HPV tests that can differentiate between clinically significant and benign, clinically insignificant infection. Evidence would indicate that clinically significant infection is linked to an abortive HPV replication cycle. In particular the later stages of the replication cycle (i.e., production of late messenger (m) RNAs and proteins) appear compromised. Compared to current DNA‐based tests which indicate only presence or absence of virus, detecting virus mRNAs by reverse transcriptase PCR (RT‐PCR) may give a more refined insight into viral activity and by implication, clinical relevance. A novel quantitative (q)RT‐PCR assay was developed for the detection of mRNAs produced late in the viral replication cycle. Initially this was validated on HPV‐containing cell lines before being applied to a panel of 223 clinical cervical samples representing the cervical disease spectrum (normal to high grade). Samples were also tested by a commercial assay which detects expression of early HPV E6/E7 oncoprotein mRNAs. Late mRNAs were found in samples associated with no, low and high grade disease and did not risk‐stratify HPV infection. The data reveal hidden complexities within the virus replication cycle and associated lesion development. This suggests that future mRNA tests for cervical disease may require quantitative detection of specific novel viral mRNAs. J. Med. Virol. 86:627–633, 2014. © 2013 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.
Role of hypoxia‐inducible factor‐1α expression in regulatory T cells on nasal polypogenesis
Authors: Jin Jun , Chang Dong‐Yeop , Kim Sung Ha , Rha Ki‐Sang , Mo Ji‐Hun , Shin Eui‐Cheol , Kim Yong Min
Published: October 2013

Objectives/Hypothesis

Hypoxia‐inducible factor‐1α (HIF‐1α) is considered as a key molecule in regulating Th17:regulatory T‐cells (Tregs) balance. The aims of this study were to investigate whether HIF‐1α is associated with the RORγ (RAR‐related orphan receptor gamma) expression of Tregs in nasal polyps and to verify whether Staphylococcus enterotoxin B (SEB) is involved in this process.

Study Design

Clinical experimental study.

Methods

Forty patients with chronic rhinosinusitis with nasal polyposis were enrolled and divided into eosinophilic nasal polyps (EPs) and noneosinophilic nasal polyps (NEPs) according to the proportion of eosinophils. Fifteen subjects who were undergoing septoplasty were enrolled as control subjects. Expression of HIF‐1α in the tissue was measured using reverse transcriptase‐polymerase chain reaction (RT‐PCR), Western blot, and flow cytometry. The mRNA expression of RORC (RAR‐related orphan receptor C) and HIF‐1α in Tregs separated from tissues were measured by RT‐PCR. Double immunofluorescent staining for RORC/FOXP3 and HIF‐1α/FOXP3 were conducted on the tissues. Expression of RORC and HIF‐1α in Tregs from peripheral blood mononuclear cells (PBMCs) was measured using flow cytometry after stimulation with SEB.

Results

Expression of RORC and HIF‐1α in Tregs was significantly higher in EPs and NEPs compared with control mucosa, and there was a significant correlation between RORC and HIF‐1α expression in Tregs. Expression of RORC and HIF‐1α mRNA in Tregs separated from the tissues was also significantly higher in nasal polyps compared with control mucosa. Expression of RORC and HIF‐1α in Tregs were increased after 24‐hour stimulation with SEB in the PBMCs.

Conclusions

HIF‐1α–induced RORC expression in Tregs may play a key role in the pathogenesis of nasal polyps.

Level of Evidence

NA Laryngoscope, 124:E151–E159, 2014
Steroids in aminoglycoside‐containing ear drops: Do they reduce cochlear toxicity?
Authors: Blakley Brian W. , Alsaleh Saad , Dewji Zameel , Qureshy Kaiser , Berard Sylvie , Xie Ling
Published: October 2013

Objectives/Hypothesis

To determine whether betamethasone (BM) reduces the cochlear toxicity of otic gentamicin (GM) if given together.

Study Design

Controlled animal study.

Methods

Thirty‐four mice were assigned at random to receive intratympanic injections of either 0.1 % BM (11 mice), 0.3% GM (13 mice), or a combination of both (GM/BM) with benzalkonium chloride (10 mice) in the left ear (treated) and saline on the right (untreated). Six injections were given on alternate days. Auditory brainstem response thresholds were assessed at 1 month, 2 months, and >2 months.

Results

There was a significantly greater degree of hearing loss in the BM‐treated ears compared to the untreated ears (6.48 dB hearing loss, P = .007) and in the GM‐treated ears compared to untreated ears (6.59 dB hearing loss, P = .010,). However, otic GM/BM and benzalkonium chloride did not cause significant additional hearing loss compared with the untreated ears (3.56 dB hearing loss, P = .242).

Conclusions

Our data suggest that hearing loss caused by GM otic drops may be reduced by the inclusion of BM and benzalkonium chloride. Our finding that BM alone was associated with hearing loss suggests that the benzalkonium chloride may be the protective agent in combination otic drops.

Level of Evidence

NA Laryngoscope, 124:1209–1213, 2014
First Example of Cyclodextrin‐Mediated Control of UCST‐Type Transitions of Vinylimidazole Terpolymers
Authors: Meiswinkel Georg , Ritter Helmut
Published: October 2013

An N‐vinylimidazole‐based monomer carrying an adamantyl group, (1‐vinyl‐2‐yl)methyl­adamantan‐1‐ylcarbamate (3), is synthesized. The terpolymerization with N‐vinylimidazole (4) and 1‐vinyl‐2‐(hydroxymethyl)imidazole (2) yields terpolymers (5a–b) with high upper critical solution temperature (UCST)‐type transitions in water. The solubility can be influenced by the addition of various amounts of randomly methylated β‐cyclodextrin (RAMEB‐CD). It is found that supramolecular host/guest interaction clearly controls the solution behavior.

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