bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of renally excreted drug dexpramipexole in subjects with impaired renal function
Authors: He Ping , Kerr Doug , Marbury Thomas , Ries Daniel , Farwell Wildon , Stecher Scott , Dong Yingwen , Wei Dong , Rogge Mark
Published: June 2014

This phase I, open‐label, single‐dose study evaluated the pharmacokinetics, safety, and tolerability of renally excreted drug dexpramipexole in subjects with normal and impaired renal function, i.e. mild, moderate, severe renal impairment, or end‐stage renal disease (ESRD) requiring hemodialysis when matched by age and sex. Dexpramipexole area under the curves (AUCs), but not Cmax, were significantly increased with the severity of renal impairment after a single dose administration. The geometric mean ratio of dose‐normalized AUC(0–72) was 1.4, 1.7, 2.7, and 4.5, respectively, in mild, moderate, severe renal impairment, and ESRD subjects when compared to healthy subjects. There was a strong association between renal function (eGFR) and dexpramipexole CLr. The slope (90% confidence interval(CI)) of eGFR and renal clearance (CLr) in the regression model was 3.1 (2.4, 3.7). Dexpramipexole elimination in ESRD subjects during both dialysis and non‐dialysis (i.e., interval between dialysis) was insignificant. Single 75 mg and 150 mg doses of dexpramipexole were well tolerated, and the safety profile was comparable across renal function groups. Extensive drug accumulation may occur with repeated dosing in patients with significant renal impairment. It is recommended that dexpramipexole not to be given to patients with severe renal impairment or in those with ESRD.
The pharmacokinetics, pharmacodynamics, and safety of baricitinib, an oral JAK 1/2 inhibitor, in healthy volunteers
Authors: Shi Jack G. , Chen Xuejun , Lee Fiona , Emm Thomas , Scherle Peggy A. , Lo Yvonne , Punwani Naresh , Williams William V. , Yeleswaram Swamy
Published: June 2014

Baricitinib (also known as LY3009104 or INCB028050), a novel and potent small molecule inhibitor of Janus kinase family of enzymes (JAKs) with selectivity for JAK1 and JAK2, is currently in clinical development for the treatment of rheumatoid arthritis (RA) and other inflammatory disorders. Two double‐blind, randomized, and placebo‐controlled studies were conducted to evaluate single ascending doses of 1–20 mg and multiple ascending doses of 2–20 mg QD and 5 mg BID for 10 or 28 days in healthy volunteers. Following oral administration, baricitinib plasma concentration typically attains its peak value within 1.5 hours postdose and subsequently declines in a bi‐exponential fashion. Baricitinib demonstrates dose‐linear and time‐invariant pharmacokinetics, with low oral‐dose clearance (17 L/h) and minimal systemic accumulation observed following repeat dosing. The mean renal clearance of baricitinib was determined to be ∼12 L/h. [Correction added after publication 12 November 2014: in the preceding sentence, “2 L/h” was changed to “12 L/h.”] The effect of a high‐fat meal on baricitinib pharmacokinetics was insignificant. The pharmacodynamics of baricitinib, evaluated by the inhibition of STAT3 phosphorylation following cytokine stimulation in the whole blood ex vivo, was well correlated with baricitinib plasma concentrations. Baricitinib was generally safe and well tolerated, with no serious treatment‐related adverse events (AEs) reported from either of the studies. An expected rapidly reversible, dose‐related decline in absolute neutrophil count was seen with baricitinib.
The Convenient Synthesis of 11‐Methyl‐3,8‐disubstituted‐12‐aryl‐3,4,7,8,9,12‐hexahydro‐1H‐chromeno[2,3‐b]quinoline‐1,10(2H)‐dione Derivatives
Authors: Han Guang‐Fan , Zhao Li‐Jun , Chen Li‐Zhuang , Du Jia‐Wei , Wang Zhong‐Xia
Published: June 2014

The 2‐arylidene‐3‐oxobutanenitrile derivatives 2 were prepared by the Knoevenagel condensation between aldehydes and 3‐oxobutanenitrile 1, which was obtained by acid hydrolysis of β‐aminocrotononitrile. 3‐Acetyl‐2‐amino‐4H‐chromen‐5(6H)‐one derivatives 3 were synthesized by reaction of 2‐arylidene‐3‐oxobutanenitrile 2 and 5‐substituted‐1,3‐cyclohexanedione in ethylene glycol. The 11‐methyl‐3,8‐disubstituted‐12‐aryl‐3,4,7,8,9,12‐hexahydro‐1H‐chromeno[2,3‐b]quinoline‐1,10(2H)‐dione derivatives 4 were obtained by Friedländer reaction of compounds 3 with 5‐substituted‐1,3‐cyclohexanedione, using p‐toluenesulfonic acid monohydrate as catalyst. The structures of all novel compounds were characterized by elemental analysis, IR, MS, and 1H NMR spectra. The crystal and molecular structure of compound 4f has been determined by single crystal XRD analysis.
Mercuric Acetate Mediated Oxidative Cyclization of (2E, 4E)‐1‐(2‐Hydroxyphenyl)‐5‐phenylpenta‐2,4‐dien‐1‐ones: Synthesis of (Z)‐2‐((E)‐3‐Phenylallylidene)benzofuran‐3(2H)‐ones
Authors: Sharma Dinesh , Makrandi Jagdish K.
Published: June 2014

(2E,4E)‐1‐(2‐Hydroxyphenyl)‐5‐phenylpenta‐2,4‐dien‐1‐ones 1a, 1b, 1c, 1d, 1e on oxidative cyclization with mercuric acetate in dimethylsulphoxide have provided (Z)‐2‐((E)‐3‐phenylallylidene)benzofuran‐3(2H)‐ones 2a, 2b, 2c, 2d, 2e in good yields.
Female Graduate Students’ Attitudes After Leadership Training
Authors: Grantham Susan , Pidano Anne E. , Whitcomb Jennifer M.
Published: June 2014

Although the increasing focus on female leadership in both the popular press and scholarly literature is relatively recent, women's leadership is not. Women have traditionally played a role in civic and cultural arenas and now have a greater opportunity to bring their particular leadership strengths to a broad range of organizations. The current paper reports on a case study about participants’ attitudes after participating in a leadership seminar series program for female graduate students at a university in the Northeast. The program's design incorporated networking, goal setting, skills training, and mentoring. Postprogram results (N = 17) on measures of Houghton and Neck's Revised Self‐Leadership Questionnaire indicated significant changes on all three of the leadership questionnaire's dimensions as well as on several subscales within the dimensions indicating that after the leadership training, the women were adapting to more transactional practices such as self‐reward and goal setting.
Curcumin protects neurons against oxygen‐glucose deprivation/reoxygenation‐induced injury through activation of peroxisome proliferator‐activated receptor‐γ function
Authors: Liu Zun‐Jing , Liu Hong‐Qiang , Xiao Cheng , Fan Hui‐Zhen , Huang Qing , Liu Yun‐Hai , Wang Yu
Published: June 2014

The turmeric derivative curcumin protects against cerebral ischemic injury. We previously demonstrated that curcumin activates peroxisome proliferator‐activated receptor‐γ (PPARγ), a ligand‐activated transcription factor involved in both neuroprotective and anti‐inflammatory signaling pathways. This study tested whether the neuroprotective effects of curcumin against oxygen–glucose deprivation/reoxygenation (OGD/R)‐induced injury of rat cortical neurons are mediated (at least in part) by PPARγ. Curcumin (10 μM) potently enhanced PPARγ expression and transcriptional activity following OGD/R. In addition, curcumin markedly increased neuronal viability, as evidenced by decreased lactate dehydrogenase release and reduced nitric oxide production, caspase‐3 activity, and apoptosis. These protective effects were suppressed by coadministration of the PPARγ antagonist 2‐chloro‐5‐nitrobenzanilide (GW9662) and by prior transfection of a small‐interfering RNA (siRNA) targeting PPARγ, treatments that had no toxic effects on healthy neurons. Curcumin reduced OGD/R‐induced accumulation of reactive oxygen species and inhibited the mitochondrial apoptosis pathway, as indicated by reduced release of cytochrome c and apoptosis‐inducing factor and maintenance of both the mitochondrial membrane potential and the Bax/Bcl‐2 ratio. Again, GW9662 or PPARγ siRNA transfection mitigated the protective effects of curcumin on mitochondrial function. Curcumin suppressed IκB kinase phosphorylation and IκB degradation, thereby inhibiting nuclear factor‐κ B (NF‐κB) nuclear translocation, effects also blocked by GW9662 or PPARγ siRNA. Immunoprecipitation experiments revealed that PPARγ interacted with NF‐κB p65 and inhibited NF‐κB activation. The present study provides strong evidence that at least some of the neuroprotective effects of curcumin against OGD/R are mediated by PPARγ activation. © 2014 Wiley Periodicals, Inc.
L‐DOPA‐induced dyskinesia in a rat model of Parkinson's disease is associated with the fluctuational release of norepinephrine in the sensorimotor striatum
Authors: Wang Yong , Wang Hui Sheng , Wang Tao , Huang Chen , Liu Jian
Published: June 2014

L‐3,4‐dihydroxyphenylalanine (L‐DOPA)‐induced dyskinesia (LID) is the most common complication of standard L‐DOPA therapy for Parkinson's disease experienced by most parkinsonian patients. LID is associated with disruption of dopaminergic homeostasis in basal ganglia following L‐DOPA administration. Norepinephrine (NE) is another important catecholaminergic neurotransmitter that is also believed to be involved in the pathogenesis of LID. This study compared NE release in the ipsilateral sensorimotor striatum of dyskinetic and nondyskinetic 6‐hydroxydopamine‐lesioned hemiparkinsonian rats treated chronically with L‐DOPA. After L‐DOPA injection, the time‐course curves of NE levels in the sensorimotor striatum were significantly different between dyskinetic and nondyskinetic rats. Several metabolic kinetic parameters of NE levels were also differentially expressed between the two groups. In comparison with nondyskinetic rats, the ΔCmax of NE was significantly higher in dyskinetic rats, whereas Tmax and t1/2 of NE were significantly shorter. Intrastriatal perfusion of NE into the lesioned sensorimotor striatum revealed a moderate dyskinesia in dyskinetic rats, which was similar to the dyskinetic behavior after L‐DOPA administration. The L‐DOPA‐related dyskinetic behavior was inhibited significantly by a further pretreatment of noradrenergic neurotoxin N‐​(2‐​chloroethyl)​‐​N‐​ethyl‐​2‐​bromobenzylamine or intrastriatal administration of the α2‐adrenoceptor antagonist idazoxan, accompanied by significant changes in metabolic kinetic parameters of NE in the sensorimotor striatum. The results provide evidence to support the correlation between abnormal NE neurotransmission and the induction of LID and suggest that the aberrant change of the quantitative and temporal releasing of NE in the sensorimotor striatum might play an important role in the pathogenesis of LID. © 2014 Wiley Periodicals, Inc.
Multi‐scalar influence of weather and climate on very large‐fires in the Eastern United States
Authors: Barbero Renaud , Abatzoglou John T. , Kolden Crystal A. , Hegewisch Katherine C. , Larkin Narasimhan K. , Podschwit Harry
Published: June 2014

A majority of area burned in the Eastern United States (EUS) results from a limited number of exceptionally large wildfires. Relationships between climatic conditions and the occurrence of very large‐fires (VLF) in the EUS were examined using composite and climate‐niche analyses that consider atmospheric factors across inter‐annual, sub‐seasonal and synoptic temporal scales. While most large‐fires in the EUS coincided with below normal fuel moisture and elevated fire weather, VLF preferentially occurred during a long‐term drought accompanied by more acute sub‐seasonal drought realized through fuel moisture stress and elevated fire‐weather conditions. These results were corroborated across the EUS, with varying influences of drought, fire danger and fire weather discriminating VLF from other large fires across different geographical regions. We also show that the probability of VLF conditioned by fire occurrence increases when long‐term drought, depleted fuel moisture and elevated fire weather align. This framework illustrates the compounding role of different timescales in VLF occurrence and serves as a basis for improving VLF predictions with seasonal climate forecasts and climate change scenarios.
Retracted: Acid‐Catalyzed Aquation of Ni(II)‐Hydrazone Complexes: Kinetics and Solvent Effect
Authors: Mohamad Ahmad Desoky M. , Rabia Mostafa K. , Ismail Nabawia M. , Mahmoud Ali Abdo
Published: June 2014

Complexes of the type [Ni(L)(H2O)]Cl2·nH2O, where L = 2‐pyridyl‐3‐isatinbishydrazone ligands, have been synthesized and characterized on the bases of elemental analysis, molar conductance, IR, electronic spectra, and thermal analysis (TGA and DTA). Acid‐catalyzed aquation of the Ni(II) isatin‐bishydrazone complexes was followed spectrophotometrically in various water–methanol and water–acetone mixtures at temperature 298 K. Kinetic behavior of the acid aquation is a linear rate law, indicating that the acid‐catalyzed aquation of these complexes in water–methanol and water–acetone mixtures follows a rate law with kobs = k2[H+]. The effect of the mole fraction of the ganic solvent, i.e., methanol and acetone, on the acid aquation has been analyzed; the decrease in the rate constant values with increasing of the methanol or acetone ratios is attributable to the effect of the co‐organic solvent on the initial states of the acid aquation by the destabilization of the H+ ion.
Nucleophilic Substitution Reactions of 2‐Methoxy‐3‐X‐5‐nitrothiophenes: Effect of Substituents and Structure–Reactivity Correlations
Authors: ECHAIEB A. , GABSI W. , BOUBAKER T.
Published: June 2014

A kinetic study is reported for reactions of 2‐methoxy‐3‐X‐5‐nitrothiophenes 1a–d (X = SO2CH3, CO2CH3, CONH2, H) with piperidine in different solvents at 20°C. It is shown that the reactions take place through a SNAr mechanism with the initial nucleophilic addition step being rate limiting. The satisfactory Hammett correlations (log k1 vs. σ) obtained in the present system confirms that a 3‐X substituent exerts an effect on the 2‐position of the same type as that exerted from the 5‐position. The second‐order rate constants associated with these reactions are employed to determine the electrophilicity parameters E of the thiophenes 1a–d according to the relationship log k (20°C) = s(E + N) (Angew. Chem., Int. Ed. Engl. 1994, 33, 938–957). The E values of 1a–d are found to cover a range from −21.33 to −17.18, going from 1d, the least reactive, to 1a, the most reactive thiophene. Interestingly, a linear correlation (r2 = 0.9910) between the electrophilicity parameters E determined in this work and the Hammett's σ constants values has been observed and discussed. On the other hand, we have found that the reported rate constants of some thiophenes 1 complexation by the methoxide ion in methanol are 3.5–73.5 times higher than predicted by Mayr's approach.
Impact of thyroid nodule size on prevalence and post‐test probability of malignancy: A systematic review
Authors: Shin Jennifer J. , Caragacianu Diana , Randolph Gregory W.
Published: June 2014

Objectives/Hypothesis

Large thyroid nodules may be associated with higher risk of malignancy and less‐accurate fine‐needle aspiration (FNA) results, but there is currently no overarching consensus. We therefore tested two null hypotheses: 1) thyroid nodule size >3 to 4 cm is not associated with a higher baseline prevalence of malignancy (i.e., the associated pretest probability is the same, regardless of size), and 2) thyroid nodule size >3 to 4 cm is not associated with worse diagnostic accuracy (i.e., the associated sensitivity, false‐negative rate, and post‐test probability of malignancy is not affected by nodule diameter).

Study Design

Computerized searches of PubMed, Embase, and The Cochrane Library through July 2013 were performed, supplemented with manual searches.

Methods

A priori criteria were defined to determine inclusion and exclusion of studies. Searches and data extraction were performed by independent reviewers and focused on FNA histopathologic findings and their relationship to nodule size, study design, and potential confounders.

Results

Criterion‐meeting studies (n = 15) included a total of 13,180 participants. The preponderance of prospective comparative studies showed a statistically significantly higher prevalence of malignancy in large nodules. Although data are mixed, evidence from the best‐reported studies suggests sensitivity, false‐negative rates, and frequency of true negatives among benign FNA results are worse in large nodules.

Conclusions

Large nodules have a higher pretest probability of malignancy. Data from larger studies suggest reduced FNA diagnostic accuracy in nodules >3 to 4 cm in diameter. Surgery represents a reasonable clinical option for nodules >3 cm.

Level of Evidence

NA Laryngoscope, 125:263–272, 2015
Classification for animal vocal fold surgery: Resection margins impact histological outcomes of vocal fold injury
Authors: Imaizumi Mitsuyoshi , Thibeault Susan L. , Leydon Ciara
Published: June 2014

Objectives/Hypothesis

Extent of vocal fold injury impacts the nature and timing of wound healing and voice outcomes. However, depth and extent of the lesion created to study wound healing in animal models vary across studies, likely contributing to different outcomes. Our goal was to create a surgery classification system to enable comparison of postoperative outcomes across animal vocal fold wound‐healing studies.

Study Design

Prospective, controlled animal study.

Methods

Rats underwent one of three types of unilateral vocal fold surgeries classified by depth and length of resection. The surgeries were: for subepithelial injury, resection of epithelium and superficial layer of the lamina propria at the midmembranous portion of the vocal fold; for transmucosal injury, resection of epithelium and lamina propria; and for transmuscular injury, resection of epithelium, lamina propria, and superficial portion of the vocalis muscle. Wound healing was evaluated histologically at various time points up to 35 days postinjury.

Results

Complete healing occurred by 14 days postsurgery for subepithelial injury, and by day 35 for transmucosal injury. Injury remained present at day 35 for transmuscular injury.

Conclusions

Timing and completeness of healing varied by extent and depth of resection. Scarless healing occurred rapidly following subepithelial injury, whereas scarring was observed at 5 weeks after transmuscular injury. The proposed classification system may facilitate comparison of surgical outcomes across vocal fold wound‐healing studies.

Levels of Evidence

N/A. Laryngoscope, 124:E437–E444, 2014
Seeing is believing: Objectively evaluating the impact of facial reanimation surgery on social perception
Authors: Dey Jacob K. , Ishii Lisa E. , Byrne Patrick J. , Boahene Kofi D. O. , Ishii Masaru
Published: June 2014

Objectives/Hypothesis

Objectively measure the ability of facial reanimation surgery to normalize the appearance of facial paralysis using eye‐tracking technology.

Study Design

Prospective randomized controlled experiment.

Methods

An eye‐tracker system was used to record the eye‐movement patterns, called scanpaths, of 86 naïve observers gazing at pictures of paralyzed faces (House‐Brackmann IV–VI), smiling and in repose; before and after facial reanimation surgery; as well as normal, nonparalyzed faces. Observers gazed at each face for 10 seconds. Fixation durations for all predefined facial areas of interest were analyzed using mixed‐effects linear regression.

Results

Observers spent the majority of time (6.6 of 10 seconds) gazing in the central triangle region (eyes, nose, and mouth) of normal faces and paralyzed faces. There were significant deviations in fixation within the central triangle of paralyzed faces as compared to normal faces. Total fixation on the eyes remained conserved. However, total nose fixation decreased and mouth fixation increased on paralyzed faces. Facial reanimation surgery normalized many of the hemifacial gaze asymmetries caused by unilateral facial paralysis, and restored a normal distribution of gaze between the functional and paralyzed sides of the face and mouth.

Conclusion

There were objective differences in the way observers directed their attention to facial features when viewing normal and paralyzed faces. After facial reanimation surgery, the attentional distraction caused by facial feature irregularities was reduced. These findings are important additions to the emerging body of objective evidence indicating the effectiveness of reanimation surgery; they also suggest opportunities to optimize reconstruction.

Level of Evidence

N/A. Laryngoscope, 124:2489–2497, 2014
Eigenvalue problems, spectral parameter power series, and modern applications
Authors: Khmelnytskaya Kira V. , Kravchenko Vladislav V. , Rosu Haret C.
Published: June 2014

In the present review, we deal with the recently introduced method of spectral parameter power series (SPPS) and show how its application leads to an explicit form of the characteristic equation for different eigenvalue problems involving Sturm–Liouville equations with variable coefficients. We consider Sturm–Liouville problems on finite intervals; problems with periodic potentials involving the construction of Hill's discriminant and Floquet–Bloch solutions; quantum‐mechanical spectral and transmission problems as well as the eigenvalue problems for the Zakharov–Shabat system. In all these cases, we obtain a characteristic equation of the problem, which in fact reduces to finding zeros of an analytic function given by its Taylor series. We illustrate the application of the method with several numerical examples, which show that at present, the SPPS method is the easiest in the implementation, the most accurate, and efficient. We emphasize that the SPPS method is not a purely numerical technique. It gives an analytical representation both for the solution and for the characteristic equation of the problem. This representation can be approximated by different numerical techniques and leads to a powerful numerical method, but most important, it offers a different insight into the spectral and transmission problems. Copyright © 2014 John Wiley & Sons, Ltd.
Depression and anxiety in amyotrophic lateral sclerosis: Correlations between the distress of patients and caregivers
Authors: Chen Dezhi , Guo Xiaoyan , Zheng Zhenzhen , Wei Qianqian , Song Wei , Cao Bei , Huang Rui , Yang Rong , Shang Huifang
Published: June 2014

Introduction: Depression and anxiety are common in amyotrophic lateral sclerosis (ALS) patients and caregivers. Methods: In this study we investigated 93 ALS patients and their 93 caregivers. Depression and anxiety were quantified by the Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, respectively. Results: Very strong correlations between depression and anxiety were found among patients and their caregivers. The severity of depression and anxiety of patients correlated moderately with that of their caregivers. No correlations were found between the severity of depression and anxiety and ALS Functional Rating Scale–Revised (ALSFRS‐R) score or for disease duration among patients and caregivers. However, severity of depression and anxiety in caregivers correlated with their age. Conclusions: Depression and anxiety in ALS patients and their caregivers were associated closely with each other but not with physical disability or disease duration in our Chinese population. Muscle Nerve 51: 353–357, 2015
Return policy: Hassle‐free or your money‐back guarantee?
Authors: Hsiao Lu , Chen Ying‐Ju
Published: June 2014

This article compares the profitability of two pervasively adopted return policies—money‐back guarantee and hassle‐free policies. In our model, a seller sells to consumers with heterogeneous valuations and hassle costs. Products are subject to quality risk, and product misfit can only be observed post‐purchase. While the hassle‐free policy is cost advantageous from the seller's viewpoint, a money‐back guarantee allows the seller to fine‐tune the consumer hassle on returning the product. Thus, when the two return policies lead to the same consumer behaviors, the hassle‐free policy dominates. Conversely, a money‐back guarantee can be more profitable even if on average, high‐valuation consumers experience a lower hassle cost than the low‐valuation ones. The optimal hassle cost can be higher when product quality gets improved; thus, it is not necessarily a perfect proxy or signal of the seller's quality. We further allow the seller to adopt a mixture of these policies, and identify the concrete operating regimes within which these return policies are optimal among more flexible policies. © 2014 Wiley Periodicals, Inc. Naval Research Logistics 61: 403–417, 2014
Water stewardship and corporate sustainability: a case study of reputation management in the food and drinks industry
Authors: Jones Peter , Hillier David , Comfort Daphne
Published: June 2014

The aim of this paper is to provide an exploratory review of the extent to which some of the leading companies in the food and drinks industry are publicly addressing water stewardship as part of their corporate sustainability strategies. The paper begins with an introductory outline of the growing importance of water stewardship and a brief discussion of corporate sustainability. The paper draws its empirical material from the most recent information on water stewardship posted by the leading companies in the food and drinks industry's corporate websites. The findings reveal that the vast majority of the selected companies address a number of elements concerning water stewardship as part of their more general approach to corporate sustainability. However, corporate commitments to water stewardship can be interpreted as being driven as much by business imperatives as by any specific concerns for environmental sustainability or a genuine desire to maintain the viability and integrity of natural ecosystems. More critically, the authors suggest that the selected companies' commitments to water stewardship are framed within existing business models focused on technological improvements in eco‐efficiency and continuing economic growth. The paper provides an accessible review of the water stewardship issues being pursued by the leading players in the food and drinks industry, and as such, it will interest academics, students, political commentators and business managers interested in water stewardship and corporate sustainability. Copyright © 2014 John Wiley & Sons, Ltd.
Long‐term benefits of inhaled corticosteroids in asthma: the propensity score method
Authors: Chanoine Sébastien , Dumas Orianne , Benmerad Meriem , Pison Christophe , Varraso Raphaëlle , Gormand Frédéric , Just Jocelyne , Le Moual Nicole , Bedouch Pierrick , Bousquet Jean , Kauffmann Francine , Pin Isabelle , Siroux Valérie
Published: June 2014

Purpose

The aim of this study was to apply a propensity score approach to assess the long‐term benefits of inhaled corticosteroids (ICS) on respiratory health in asthma.

Methods

This analysis was conducted on adults with persistent asthma from the Epidemiological study on the Genetics and Environment of Asthma, a 12‐year follow‐up study. ICS exposure was assessed by questionnaire. Change in lung function over the follow‐up period, asthma control, and health‐related quality of life (asthma quality of life questionnaire) were assessed by standardized and validated methods.

Results

Among 245 adults with persistent asthma, 78 (31.8%) were regularly/continuously exposed to ICS (≥6 months/year, ICS++) and 167 never/irregularly exposed to ICS (<6 months/year, ICS+/−) over the follow‐up period. Compared with ICS+/− subjects, a nonsignificant trend for a slower lung function decline (mL/year) was observed in ICS++ subjects (β [95%CI] = −11.4 [−24.9; 2.0]). The ICS++ subjects did not have better controlled asthma and higher health‐related quality of life as compared with ICS+/− subjects.

Conclusions

Applying a propensity score method did not offer evidence of a statistical significant long‐term benefit of ICS on respiratory health in adults with persistent asthma regularly or continuously exposed to ICS over a long period. Copyright © 2014 John Wiley & Sons, Ltd.
El Harka: Perceptions of the Migration‐Development Nexus in Post‐Revolution Tunis
Authors: Harris Jonathan
Published: June 2014

In the 3 years since the ousting of Tunisia's dictator Zine El Abedine Ben Ali in January 2011, net emigration from Tunisia has doubled, suggesting a link between revolutionary politics and aspirations to emigrate. A large proportion of this emigration has taken the form of a clandestine crossing to Europe, locally called El Harka. This paper explores the complex interactions between the ‘migration‐development nexus’ and revolutionary national politics in the aspirations of Tunisian young men to emigrate in the post‐Revolution period. I use the sociologist Albert O. Hirschman's concept of ‘Exit‐Voice‐Loyalty’ to come to an understanding of the geographical imaginaries and spatial practices expressed by individual Tunisian men in relation to migration. I present my findings within a typology of ‘surplus’, ‘circulation’, and ‘engagement’ to describe the ways in which the inherent politics of migration are expressed. ‘Surplus’ emerged as a powerful discourse in post‐Revolution Tunis, leading to politically significant notions of migrant identity. ‘Circulation’ denotes the developmental ideal held in tension with concerns over legality. I argue that the primacy of illegal emigration from Tunisia indicates the dominance of exploitative migration policies. Finally, political ‘engagement’ in the post‐Revolution period is theorised to correlate to disinterest in emigration. The institution of freedom of expression is argued to increase ‘loyalty’, through privileging ‘voice’ over ‘exit’ as a course of action for the discontent. Copyright © 2014 John Wiley & Sons, Ltd.
Flexibility in Men's Sexual Practices in Response to Iatrogenic Erectile Dysfunction after Prostate Cancer Treatment
Authors: Dowsett G. W. , Lyons A. , Duncan D. , Wassersug R. J.
Published: June 2014

Introduction

Prostate cancer (PCa) treatments are associated with a high incidence of erectile dysfunction (ED). Interventions to help men with iatrogenic ED have largely focused on penile tumescence adequate for vaginal penetration. Less research has been undertaken on sex practices other than penile/vaginal intercourse.

Aim

The aim of this study was to explore forms of sexual practice engaged in by men following treatment for PCa. We focused in particular on anal intercourse (AI) as practiced by both nonheterosexual (i.e., gay-identified men and other men who have sex with men) and heterosexual men. We sought to determine how common AI was subsequent to PCa treatment and how flexible AI practitioners were in their modes (e.g., from insertive to receptive) when faced with iatrogenic ED.

Methods

An international online survey was conducted in 2010–2011 of men treated for PCa, where participants (N = 558) were asked explicitly about their sexual practices before and after PCa treatment.

Main Outcome Measures

The outcome measures were the numbers and percentages of men who practiced AI before and after PCa treatment as well as the percentage who changed AI practice after PCa treatment.

Results

Five hundred twenty-six men (90 nonheterosexual men; 436 heterosexual men) answered questions on AI practices. A proportion of nonheterosexual (47%) and heterosexual men (7%) practiced AI following PCa treatment, and did so in all modes (insertive, receptive, and “versatile”). Many nonheterosexual men continued to be sexually active in the face of iatrogenic ED by shifting from the insertive to receptive modes. A few men, both heterosexual and nonheterosexual, adopted AI for the first time post-PCa treatment.

Conclusions

Flexibility in sexual practice is possible for some men, both nonheterosexual and heterosexual, in the face of iatrogenic ED. Advising PCa patients of the possibilities of sexual strategies that include AI may help them in reestablishing a sex life that is not erection dependent.
Ultra‐Specific Zeptomole MicroRNA Detection by Plasmonic Nanowire Interstice Sensor with Bi‐Temperature Hybridization
Authors: Kang Taejoon , Kim Hongki , Lee Jeong Min , Lee Hyoban , Choi Yun‐Seok , Kang Gyeongwon , Seo Min‐Kyo , Chung Bong Hyun , Jung Yongwon , Kim Bongsoo
Published: June 2014

MicroRNAs (miRNAs) are emerging new biomarkers for many human diseases. To fully employ miRNAs as biomarkers for clinical diagnosis, it is most desirable to accurately determine the expression patterns of miRNAs. The optimum miRNA profiling method would feature 1) highest sensitivity with a wide dynamic range for accurate expression patterns, 2) supreme specificity to discriminate single nucleotide polymorphisms (SNPs), and 3) simple sensing processes to minimize measurement variation. Here, an ultra‐specific detection method of miRNAs with zeptomole sensitivity is reported by applying bi‐temperature hybridizations on single‐crystalline plasmonic nanowire interstice (PNI) sensors. This method shows near‐perfect accuracy of SNPs and a very low detection limit of 100 am (50 zeptomole) without any amplification or labeling steps. Furthermore, multiplex sensing capability and wide dynamic ranges (100 am–100 pm) of this method allows reliable observation of the expression patterns of miRNAs extracted from human tissues. The PNI sensor offers combination of ultra‐specificity and zeptomole sensitivity while requiring two steps of hybridization between short oligonucleotides, which could present the best set of features for optimum miRNA sensing method.
Nitric Oxide-Induced Murine Hematopoietic Stem Cell Fate Involves Multiple Signaling Proteins, Gene Expression, and Redox Modulation
Authors: Nogueira-Pedro Amanda , Dias Carolina C. , Regina Helena , Segreto C. , Addios Priscilla C. , Lungato Lisandro. , D’Almeida Vania , Barros Carlos C. , Higa Elisa M. S. , Buri Marcus V. , Ferreira Alice T. , Paredes-Gamero Edgar Julian
Published: June 2014

There are a growing number of reports showing the influence of redox modulation in cellular signaling. Although the regulation of hematopoiesis by reactive oxygen species (ROS) and reactive nitrogen species (RNS) has been described, their direct participation in the differentiation of hematopoietic stem cells (HSCs) remains unclear. In this work, the direct role of nitric oxide (NO•), a RNS, in the modulation of hematopoiesis was investigated using two sources of NO•, one produced by endothelial cells stimulated with carbachol in vitro and another using the NO•-donor S-nitroso-N-acetyl-d,l-penicillamine (SNAP) in vivo. Two main NO• effects were observed: proliferation of HSCs—especially of the short-term HSCs—and its commitment and terminal differentiation to the myeloid lineage. NO•-induced proliferation was characterized by the increase in the number of cycling HSCs and hematopoietic progenitor cells positive to BrdU and Ki-67, upregulation of Notch-1, Cx43, PECAM-1, CaR, ERK1/2, Akt, p38, PKC, and c-Myc. NO•-induced HSCs differentiation was characterized by the increase in granulocytic-macrophage progenitors, granulocyte–macrophage colony forming units, mature myeloid cells, upregulation of PU.1, and C/EBPα genes concomitantly to the downregulation of GATA-3 and Ikz-3 genes, activation of Stat5 and downregulation of the other analyzed proteins mentioned above. Also, redox status modulation differed between proliferation and differentiation responses, which is likely associated with the transition of the proliferative to differentiation status. Our findings provide evidence of the role of NO• in inducing HSCs proliferation and myeloid differentiation involving multiple signaling. Stem Cells  2014;32:2949–2960
Targeting the bHLH Transcriptional Networks by Mutated E Proteins in Experimental Glioma
Authors: Beyeler Sarah , Joly Sandrine , Fries Michel , Obermair Franz-Josef , Burn Felice , Mehmood Rashid , Tabatabai Ghazaleh , Raineteau Olivier
Published: June 2014

Glioblastomas (GB) are aggressive primary brain tumors. Helix-loop-helix (HLH, ID proteins) and basic HLH (bHLH, e.g., Olig2) proteins are transcription factors that regulate stem cell proliferation and differentiation throughout development and into adulthood. Their convergence on many oncogenic signaling pathways combined with the observation that their overexpression in GB correlates with poor clinical outcome identifies these transcription factors as promising therapeutic targets. Important dimerization partners of HLH/bHLH proteins are E proteins that are necessary for nuclear translocation and DNA binding. Here, we overexpressed a wild type or a dominant negative form of E47 (dnE47) that lacks its nuclear localization signal thus preventing nuclear translocation of bHLH proteins in long-term glioma cell lines and in glioma-initiating cell lines and analyzed the effects in vitro and in vivo. While overexpression of E47 was sufficient to induce apoptosis in absence of bHLH proteins, dnE47 was necessary to prevent nuclear translocation of Olig2 and to achieve similar proapoptotic responses. Transcriptional analyses revealed downregulation of the antiapoptotic gene BCL2L1 and the proproliferative gene CDC25A as underlying mechanisms. Overexpression of dnE47 in glioma-initiating cell lines with high HLH and bHLH protein levels reduced sphere formation capacities and expression levels of Nestin, BCL2L1, and CDC25A. Finally, the in vivo induction of dnE47 expression in established xenografts prolonged survival. In conclusion, our data introduce a novel approach to jointly neutralize HLH and bHLH transcriptional networks activities, and identify these transcription factors as potential targets in glioma. Stem Cells  2014;32:2583–2595
The impact of viscoelastic behavior and viscosity ratio on the phase behavior and morphology of polypropylene/polybutene‐1 blends
Authors: Ardakani Farzaneh , Jahani Yousef , Morshedian Jalil
Published: June 2014

In this study, the influence of the viscosity ratio on the rheology, morphology, and interfacial interaction of polypropylene and polybutene‐1 (PB‐1) resins with various melt flow behaviors in the blend are investigated. A droplet‐matrix morphology is observed in the scanning electron microscope images for all formulations and the size of particles increased proportionally by increasing the viscosity ratio. Viscoelastic parameters of blends at various viscosity ratios and compositions are measured by small‐amplitude oscillation rheometry in the linear viscoelastic region. The Cole‐Cole plots showed a nearly semicircular arc for all compositions. This semicircular arc is observed while the viscosity ratio is lower than 1, and the Cole‐Cole plots deviated from the semicircular shape at PB‐1 content higher than 10 wt%. It is emphasized that, in addition to compatibility, the semi‐circularity of Cole‐Cole plots affects the size of the dispersed particles, which is under the influence of the viscosity ratio. It is found that the interfacial tensions of polypropylene and PB‐1 are not significantly different when changing the viscosity ratio and coarsening the morphology. The form relaxation times in the blends with lower viscosity ratios are shorter than the form relaxation times of the blends with higher viscosity ratios. J. VINYL ADDIT. TECHNOL. 21:94–101, 2015. © 2014 Society of Plastics Engineers
Effect of organic montmorillonite on the hot storage stability of asphalt modified by waste packaging polyethylene
Authors: Fang Changqing , Zhang Ying , Yu Ruien , Liu Xiaolong , Hu Jingbo , Zhang Maorong
Published: June 2014

In this paper, waste polyethylene (WPE), a large class of waste plastic packaging, and organic montmorillonite (OMMT) were employed as the polymer modifier and additive to modify base asphalt, and then hot storage stability of modified asphalt was studied. Structure of the modified asphalt was characterized with X‐ray diffraction and fluorescence microscopy. Moreover, the hot storage stability of WPE‐modified asphalt was investigated by Fourier‐transform infrared analysis, differential scanning calorimetry, and thermal gravimetry. Results show that an exfoliated structure is formed in the modified asphalt after adding OMMT. The WPE modifier particles become smaller and are more uniformly dispersed in the modified asphalt system after adding OMMT. Also, the addition of OMMT effectively improves the hot storage stability of the modified asphalt. The OMMT not only increases the compatibility between the WPE modifier and base asphalt but enhances the homogeneity of the modified asphalt at extreme temperatures. Heat capacity and phase behavior of modified asphalt after adding OMMT are changed; in the meantime, the thermal stability of the modified asphalt increases. J. VINYL ADDIT. TECHNOL., 21:89–93, 2015. © 2014 Society of Plastics Engineers
One grammar or two? Sign Languages and the Nature of Human Language
Authors: Lillo‐Martin Diane C. , Gajewski Jon
Published: June 2014

Linguistic research has identified abstract properties that seem to be shared by all languages—such properties may be considered defining characteristics. In recent decades, the recognition that human language is found not only in the spoken modality but also in the form of sign languages has led to a reconsideration of some of these potential linguistic universals. In large part, the linguistic analysis of sign languages has led to the conclusion that universal characteristics of language can be stated at an abstract enough level to include languages in both spoken and signed modalities. For example, languages in both modalities display hierarchical structure at sub‐lexical and phrasal level, and recursive rule application. However, this does not mean that modality‐based differences between signed and spoken languages are trivial. In this article, we consider several candidate domains for modality effects, in light of the overarching question: are signed and spoken languages subject to the same abstract grammatical constraints, or is a substantially different conception of grammar needed for the sign language case? We look at differences between language types based on the use of space, iconicity, and the possibility for simultaneity in linguistic expression. The inclusion of sign languages does support some broadening of the conception of human language—in ways that are applicable for spoken languages as well. Still, the overall conclusion is that one grammar applies for human language, no matter the modality of expression. WIREs Cogn Sci 2014, 5:387–401. doi: 10.1002/wcs.1297

This article is categorized under:

Linguistics > Linguistic Theory
Time perception: the bad news and the good
Authors: Matthews William J. , Meck Warren H.
Published: June 2014

Time perception is fundamental and heavily researched, but the field faces a number of obstacles to theoretical progress. In this advanced review, we focus on three pieces of ‘bad news’ for time perception research: temporal perception is highly labile across changes in experimental context and task; there are pronounced individual differences not just in overall performance but in the use of different timing strategies and the effect of key variables; and laboratory studies typically bear little relation to timing in the ‘real world’. We describe recent examples of these issues and in each case offer some ‘good news’ by showing how new research is addressing these challenges to provide rich insights into the neural and information‐processing bases of timing and time perception. WIREs Cogn Sci 2014, 5:429‐446. doi: 10.1002/wcs.1298

This article is categorized under:

Psychology > Perception and Psychophysics

Neuroscience > Cognition
Scaling relation for low energy states in a single‐slip model in finite crystal plasticity
Authors: Schubert T.
Published: June 2014

We derive a scaling‐relation, for the infimum of the energyurn:x-wiley:00442267:media:zamm201300213:zamm201300213-math-0001for small ϵ,δ > 0, where p, q ≥ 1, u: Ω → ℝ2is a deformation with suitable affine boundary conditions and γ: Ω → ℝ is a suitable slip variable. This model is motivated by a two‐dimensional single‐slip model in finite crystal plasticity. We show, that the infimum of the energy Jϵ,δscales as. This scaling‐relation is attained by an asymptotically self‐similar branching construction.
Neighborhood Racial Composition, Racial Discrimination, and Depressive Symptoms in African Americans
Authors: English Devin , Lambert Sharon F. , Evans Michele K. , Zonderman Alan B.
Published: June 2014

While evidence indicates that experienced racial discrimination is associated with increased depressive symptoms for African Americans, there is little research investigating predictors of experienced racial discrimination. This paper examines neighborhood racial composition and sociodemographic factors as antecedents to experienced racial discrimination and resultant levels of depressive symptoms among African American adults. The sample included 505 socioeconomically‐diverse African American adults from Baltimore, MD. Study data were obtained via self‐report and geocoding of participant addresses based on 2010 census data. Study hypotheses were tested using multiple pathways within a longitudinal Structural Equation Model. Experienced racial discrimination was positively associated with age and sex such that older individuals and males experienced increased levels of racial discrimination. In addition, the percentage of White individuals residing in a neighborhood was positively associated with levels of experienced racial discrimination for African American neighborhood residents. Experienced racial discrimination was positively associated with later depressive symptoms. Neighborhood‐level contextual factors such as neighborhood racial composition and individual differences in sociodemographic characteristics appear to play an important role in the experience of racial discrimination and the etiology of depression in African American adults.
Winter warming pulses differently affect plant performance in temperate heathland and grassland communities
Authors: Schuerings Jan , Jentsch Anke , Walter Julia , Kreyling Juergen
Published: June 2014

Winter air temperature variability is projected to increase in the temperate zone whereas snow cover is projected to decrease, leading to more variable soil temperatures. In a field experiment winter warming pulses were applied and aboveground biomass and root length of four plant species were quantified over two subsequent growing seasons in monocultures and mixtures of two species. The experiment was replicated at two sites, a colder upland site with more snow and a warmer, dryer lowland site. Aboveground biomass of Holcus lanatus declined (−29 %) in the growing season after the warming pulse treatment. Its competitor in the grassland mixture, Plantago lanceolata, profited from this decline by increased biomass production (+18 %). These effects disappeared in the second year. There was a strong decline in biomass for P. lanceolata at the lowland site in the second year. These two species also showed a decline in leaf carbohydrate content during the manipulation. Aboveground productivity and carbohydrate content of the heathland species was not affected by the treatment. The aboveground effects of the treatment did not differ significantly between the two sites, thereby implying some generality for different temperate ecosystems with little and significant amount of snowfall. Root length increased directly after the treatment for H. lanatus and for Calluna vulgaris with a peak at the end of the first growing season. The observed species‐specific effects emphasize the ecological importance of winter temperature variability in the temperate zone and appear important for potential shifts in community composition and ecosystem productivity.
Beneficios y perjuicios de la estrategia de imitación
Authors: Arboleda Ana María
Published: June 2014

Este artículo analiza la estrategia de imitación resaltando sus potenciales beneficios y perjuicios. Utilizando una metodología exploratoria, se usan 15 casos en los que se argumenta competencia desleal por imitación. La discusión ofrece un paralelo entre las razones que tiene una empresa para imitar y para no hacerlo. Se concluye que la imitación es una estrategia viable siempre que la marca se reconozca como atributo distintivo, al tiempo que las marcas seguidoras ganan participación de mercado y comunican atributos acordes a la categoría. Por el contrario, si la imitación afecta negativamente el esfuerzo de una marca por ser distintiva, vulnera la decisión del consumidor al generar confusión y desmotiva el esfuerzo empresarial por la innovación.