bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of acute and chronic ecotoxicity data in environmental risk assessment of pharmaceuticals
Authors: Vestel Jessica , Caldwell Daniel J. , Constantine Lisa , D'Aco Vincent J. , Davidson Todd , Dolan David G. , Millard Steven P. , Murray-Smith Richard , Parke Neil J. , Ryan Jim J. , Straub Jürg Oliver , Wilson Peter
Published: September 2015

For many older pharmaceuticals, chronic aquatic toxicity data are limited. To assess risk during development, scale-up, and manufacturing processes, acute data and physicochemical properties need to be leveraged to reduce potential long-term impacts to the environment. Aquatic toxicity data were pooled from daphnid, fish, and algae studies for 102 active pharmaceutical ingredients (APIs) to evaluate the relationship between predicted no-effect concentrations (PNECs) derived from acute and chronic tests. The relationships between acute and chronic aquatic toxicity and the n-octanol/water distribution coefficient (DOW) were also characterized. Statistically significant but weak correlations were observed between toxicity and log DOW, indicating that DOW is not the only contributor to toxicity. Both acute and chronic PNEC values could be calculated for 60 of the 102 APIs. For most compounds, PNECs derived from acute data were lower than PNECs derived from chronic data, with the exception of steroid estrogens. Seven percent of the PNECs derived from acute data were below the European Union action limit of 0.01 μg/L and all were anti-infectives affecting algal species. Eight percent of available PNECs derived from chronic data were below the European Union action limit, and fish were the most sensitive species for all but 1 API. These analyses suggest that the use of acute data may be acceptable if chronic data are unavailable, unless specific mode of action concerns suggest otherwise. Environ Toxicol Chem 2016;35:1201–1212. © 2015 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.
Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice
Authors: Gariani Karim , Menzies Keir J. , Ryu Dongryeol , Wegner Casey J. , Wang Xu , Ropelle Eduardo R. , Moullan Norman , Zhang Hongbo , Perino Alessia , Lemos Vera , Kim Bohkyung , Park Young‐Ki , Piersigilli Alessandra , Pham Tho X. , Yang Yue , Ku Chai Siah , Koo Sung I. , Fomitchova Anna , Cantó Carlos , Schoonjans Kristina , Sauve Anthony A. , Lee Ji‐Young , Auwerx Johan
Published: September 2015

With no approved pharmacological treatment, nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease in Western countries and its worldwide prevalence continues to increase along with the growing obesity epidemic. Here, we show that a high‐fat high‐sucrose (HFHS) diet, eliciting chronic hepatosteatosis resembling human fatty liver, lowers hepatic nicotinamide adenine dinucleotide (NAD+) levels driving reductions in hepatic mitochondrial content, function, and adenosine triphosphate (ATP) levels, in conjunction with robust increases in hepatic weight, lipid content, and peroxidation in C57BL/6J mice. To assess the effect of NAD+ repletion on the development of steatosis in mice, nicotinamide riboside, a precursor of NAD+ biosynthesis, was added to the HFHS diet, either as a preventive strategy or as a therapeutic intervention. We demonstrate that NR prevents and reverts NAFLD by inducing a sirtuin (SIRT)1‐ and SIRT3‐dependent mitochondrial unfolded protein response, triggering an adaptive mitohormetic pathway to increase hepatic β‐oxidation and mitochondrial complex content and activity. The cell‐autonomous beneficial component of NR treatment was revealed in liver‐specific Sirt1 knockout mice (Sirt1hep−/−
), whereas apolipoprotein E‐deficient mice (Apoe
−/−) challenged with a high‐fat high‐cholesterol diet affirmed the use of NR in other independent models of NAFLD. Conclusion: Our data warrant the future evaluation of NAD+ boosting strategies to manage the development or progression of NAFLD. (Hepatology 2016;63:1190–1204)
Differing impact of the deletion of hemochromatosis‐associated molecules HFE and transferrin receptor‐2 on the iron phenotype of mice lacking bone morphogenetic protein 6 or hemojuvelin
Authors: Latour Chloé , Besson‐Fournier Céline , Meynard Delphine , Silvestri Laura , Gourbeyre Ophélie , Aguilar‐Martinez Patricia , Schmidt Paul J. , Fleming Mark D. , Roth Marie‐Paule , Coppin Hélène
Published: September 2015

Hereditary hemochromatosis, which is characterized by inappropriately low levels of hepcidin, increased dietary iron uptake, and systemic iron accumulation, has been associated with mutations in the HFE, transferrin receptor‐2 (TfR2), and hemojuvelin (HJV) genes. However, it is still not clear whether these molecules intersect in vivo with bone morphogenetic protein 6 (BMP6)/mothers against decapentaplegic (SMAD) homolog signaling, the main pathway up‐regulating hepcidin expression in response to elevated hepatic iron. To answer this question, we produced double knockout mice for Bmp6 and β2‐microglobulin (a surrogate for the loss of Hfe) and for Bmp6 and Tfr2, and we compared their phenotype (hepcidin expression, Bmp/Smad signaling, hepatic and extrahepatic tissue iron accumulation) with that of single Bmp6‐deficient mice and that of mice deficient for Hjv, alone or in combination with Hfe or Tfr2. Whereas the phenotype of Hjv‐deficient females was not affected by loss of Hfe or Tfr2, that of Bmp6‐deficient females was considerably worsened, with decreased Smad5 phosphorylation, compared with single Bmp6‐deficient mice, further repression of hepcidin gene expression, undetectable serum hepcidin, and massive iron accumulation not only in the liver but also in the pancreas, the heart, and the kidneys. Conclusion: These results show that (1) BMP6 does not require HJV to transduce signal to hepcidin in response to intracellular iron, even if the loss of HJV partly reduces this signal, (2) another BMP ligand can replace BMP6 and significantly induce hepcidin expression in response to extracellular iron, and (3) BMP6 alone is as efficient at inducing hepcidin as the other BMPs in association with the HJV/HFE/TfR2 complex; they provide an explanation for the compensatory effect of BMP6 treatment on the molecular defect underlying Hfe hemochromatosis in mice. (Hepatology 2016;63:126–137)
Factors influencing the calculation of periodic secondary circulation in a tidal river: numerical modelling of the lower Sacramento River, USA
Authors: Bever Aaron J. , MacWilliams Michael L.
Published: September 2015

Secondary circulation is the component of three‐dimensional (3D) flow in river channels perpendicular to the primary flow direction. Secondary circulation calculated from acoustic Doppler current profiler (ADCP) transects is sensitive to the calculation method and is affected by the transect angle relative to the mean flow direction and variations in the flow direction along a transect. To quantify bounds on transect alignment relative to river flow for field data collection and examine tidal time‐scale variability in secondary circulation, the 3D hydrodynamic model UnTRIM was applied to simulate the hydrodynamics in the lower reach of the Sacramento River (CA, USA). Secondary circulation was calculated using the Rozovskii and the zero net discharge methods on repeated transects extracted from the model results in regions of both relatively uniform and complex flows. When the depth‐averaged flow direction along a transect varied by more than about 5 °, occurring when the transect was as little as 10 to 20 ° out of normal to the mean flow direction, the Rozovskii method produced more realistic secondary circulation than the zero net discharge method. Analysis indicated that ADCP transects should be within 20 ° of perpendicular to the mean flow direction when calculating secondary circulation. Secondary circulation strength around two tidally influenced bends generally increased with increasing flow and broke down near slack water. However, the strength of the secondary circulation was not only a function of the flow magnitude, but also depended on the direction of the water flow and the transect location relative to the river curvature, which varied with the tidal flow direction. Copyright © 2015 John Wiley & Sons, Ltd.
Functional profile of S100A4‐deficient T cells
Authors: Weatherly Kathleen , Bettonville Marie , Torres David , Kohler Arnaud , Goriely Stanislas , Braun Michel Y.
Published: September 2015

The protein S100A4 is best known for its significant role in promoting motility and invasive capacity of cancer cells. Since S100A4 expression has been reported also in T cells, we analyzed its potential role in T cell motility and inflammation. Using S100a4+/Gfp mice, we show here that S100A4 is exclusively expressed by memory T cells of CD4+ or CD8+ subpopulations, predominantly of the effector memory T cell subtype. However, the protein was not required for in vitro memory T cell migration toward gradients of the inflammatory chemokine CXCL10. Moreover, T cell memory response was normal in S100A4‐deficient mice and lack of S100a4 gene expression did not induce any defect in promoting the development of protective immunity or inflammatory reactions leading to autoimmunity. Taken together, our results demonstrate that S100A4 activity is dispensable for T cell motility/migration and inflammatory potential.
Teaching observational learning to children with autism
Authors: MacDonald Jacquelyn , Ahearn William H.
Published: September 2015

Observational learning (OL) is critical for the acquisition of social skills and may be an important skill for learning in traditional educational settings. Although OL occurs during early childhood in the typically developing population, research suggests that it may be limited in children diagnosed with autism spectrum disorder (ASD). The purpose of the present study was to develop an assessment to test for the presence of OL across a variety of tasks. If OL was deficient, we sought to teach it by training specific skills. Six participants who had been diagnosed with ASD demonstrated deficits in OL. After an initial assessment, a multiple‐probe design across OL tasks showed that training produced acquisition of these skills across multiple exemplars. After training, 5 of the 6 participants engaged in OL across multiple tasks and task variations, demonstrating generalization. For 1 participant, generalization of performance did not occur across tasks but did occur within task variations.
Graduated guidance delivered by parents to teach yoga to children with developmental delays
Authors: Gruber Deborah J. , Poulson Claire L.
Published: September 2015

We evaluated the effects of a parent‐implemented intervention to teach yoga poses to 3 children with developmental delays. Graduated guidance, provided by the participants' mothers, was introduced in a multiple baseline design across the participants. With the introduction of intervention, imitation of the response chains increased over baseline for all participants. Generalization to novel and live models occurred for 2 participants. Results are discussed in terms of using behavior‐analytic procedures to teach physical fitness activities to individuals with developmental disabilities.
Oxidation and other property changes of a remelted highly crosslinked UHMWPE in retrieved tibial bearings
Authors: Reinitz Steven D. , Currier Barbara H. , Levine Rayna A.C. , Collier John P. , Van Citters Douglas W.
Published: September 2015

This study examined retrieved UHMWPE tibial bearings made from a remelted highly crosslinked (HXL) UHMWPE to determine whether the material is chemically stable in vivo. Retrieved tibial components were measured for changes in ketone oxidation and crosslink density. Oxidation increased with in vivo duration, and a significant decrease in crosslink density with increased mean ketone oxidation index was observed. These results suggest that in vivo oxidation is causing material degradation. Furthermore, a subsurface whitened damage region was found below the articular surface of one bearing, indicating the possibility of a clinically relevant decrease in mechanical properties of this component. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 39–45, 2017.
Cathepsin-Mediated Alterations in TGFß-Related Signaling Underlie Disrupted Cartilage and Bone Maturation Associated With Impaired Lysosomal Targeting
Authors: Flanagan-Steet Heather , Aarnio Megan , Kwan Brian , Guihard Pierre , Petrey Aaron , Haskins Mark , Blanchard Frederic , Steet Richard
Published: September 2015

Hypersecretion of acid hydrolases is a hallmark feature of mucolipidosis II (MLII), a lysosomal storage disease caused by loss of carbohydrate-dependent lysosomal targeting. Inappropriate extracellular action of these hydrolases is proposed to contribute to skeletal pathogenesis, but the mechanisms that connect hydrolase activity to the onset of disease phenotypes remain poorly understood. Here we link extracellular cathepsin K activity to abnormal bone and cartilage development in MLII animals by demonstrating that it disrupts the balance of TGFß-related signaling during chondrogenesis. TGFß-like Smad2,3 signals are elevated and BMP-like Smad1,5,8 signals reduced in both feline and zebrafish MLII chondrocytes and osteoblasts, maintaining these cells in an immature state. Reducing either cathepsin K activity or expression of the transcriptional regulator Sox9a in MLII zebrafish significantly improved phenotypes. We further identify components of the large latent TGFß complex as novel targets of cathepsin K at neutral pH, providing a possible mechanism for enhanced Smad2,3 activation in vivo. These findings highlight the complexity of the skeletal disease associated with MLII and bring new insight to the role of secreted cathepsin proteases in cartilage development and growth factor regulation. © 2015 American Society for Bone and Mineral Research.
Depletion of hormones and antimicrobials in cattle manure using thermophilic anaerobic digestion
Authors: Withey Jonathan M , Mugo Samuel M , Zhou Ting , Rosser Patrick M , Gao Tiejun
Published: September 2015

BACKGROUND

The fate and effect of hormone and antimicrobial residues in the manure of therapeutically treated cattle is of considerable concern because of the adverse effects of environmental loading of these chemicals. The objective of this study was to determine the depletion of tylosin (TYL), chlortetracycline (CTC), sulfamethazine (SMZ) and megestrol (MEG) using thermophilic anaerobic digestion (TAD).

RESULTS

Quantitative methods using HPLC‐DAD‐MS/MS analysis were developed to monitor the hormone and antimicrobials, spiked into manure obtained from unmedicated cattle. These manure samples were incubated for a 28‐day period, during which hormone and antimicrobial depletion, and biogas production, was determined. Significant depletion of TYL, CTC, SMZ and MEG was demonstrated using TAD. Both TYL and CTC underwent complete depletion, while SMZ and MEG were each 80% depleted by the 28th day of incubation. The presence of antimicrobials had no negative effects on process stability and caused no significant reduction in total methane production.

CONCLUSION

This process has demonstrated value in reducing the hormone and antimicrobial load to the environment, while not compromising economic value of the biogas production, and allowing use of post‐digested biosolids as a regenerated fertilizer. © 2015 Society of Chemical Industry
Metabolomic analysis can detect the composition of pasta enriched with fibre after cooking
Authors: Beleggia Romina , Menga Valeria , Platani Cristiano , Nigro Franca , Fragasso Mariagiovanna , Fares Clara
Published: September 2015

BACKGROUND

Several studies have demonstrated that metabolomics has a definite place in food quality, nutritional value, and safety issues. The aim of the present study was to determine and compare the metabolites in different pasta samples with fibre, and to investigate the modifications induced in these different kinds of pasta during cooking, using a gas chromatography–mass spectrometry‐based metabolomics approach.

RESULTS

Differences were seen for some of the amino acids, which were absent in control pasta, while were present both in the commercially available high‐fibre pasta (samples A–C) and the enriched pasta (samples D–F). The highest content in reducing sugars was observed in enriched samples in comparison with high‐fibre pasta. The presence of stigmasterol in samples enriched with wheat bran was relevant. Cooking decreased all of the metabolites: the high‐fibre pasta (A–C) and Control showed losses of amino acids and tocopherols, while for sugars and organic acids, the decrease depended on the pasta sample. The enriched pasta samples (D–F) showed the same decreases with the exception of phytosterols, and in pasta with barley the decrease of saturated fatty acids was not significant as for tocopherols in pasta with oat. Principal component analysis of the metabolites and the pasta discrimination was effective in differentiating the enriched pasta from the commercial pasta, both uncooked and cooked.

CONCLUSIONS

The study has established that such metabolomic analyses provide useful tools in the evaluation of the changes in nutritional compounds in high‐fibre and enriched pasta, both before and after cooking. © 2015 Society of Chemical Industry
The disease recurrence rate after the canal wall up or canal wall down technique in adults
Authors: Kerckhoffs Kelly G. P. , Kommer Maarten B. J. , van Strien Thom H. L. , Visscher Simeon J. A. , Bruijnzeel Hanneke , Smit Adriana L. , Grolman Wilko
Published: September 2015

Objectives/Hypothesis

To review which type of cholesteatoma surgery, canal wall up (CWU) or canal wall down (CWD), provides the lowest risk for residual and/or recurrent disease in adults with primary acquired cholesteatoma.

Data Sources

PubMed, Embase, CINAHL, the Cochrane Library, Scopus and Web of Science.

Study Design

We selected articles comparing CWU with CWD, reporting on disease recidivism (combined residual and recurrent disease) or independent residual or disease recurrence rates. We included studies with a moderate to high relevance.

Results

Our search yielded 2,060 articles. We selected seven studies that carried a moderate risk of bias. Six studies described higher disease recidivism after the CWU procedure [16.7–61.0%] compared to the CWD technique [0–13.2%]. Four studies showed statistical significant difference (P < .05). One study showed opposite results: recidivism was found in 7.8% CWU and in 22.1% CWD cases (P < .001). Studies showed CWU recidivism more likely to be residual disease, whereas CWD recidivism tended to be recurrent disease.

Conclusion

The majority of included studies showed CWU to result in more disease recidivism compared to the CWD technique in adult patients with a primary acquired cholesteatoma. If recidivism risk is the most important factor to consider a certain surgical technique, we recommend application of the CWD procedure. However, many additional factors in patient care will define the best treatment decision, such as residual hearing and access to health care. Our recommendations are based on Level II evidence, which underlines the need for future high‐level evidence studies. Laryngoscope, 126:980–987, 2016
The efficacy of gabapentin/pregabalin in improving pain after tonsillectomy: A meta‐analysis
Authors: Hwang Se Hwan , Park In Joon , Cho Young Jin , Jeong Yeon Min , Kang Jun Myung
Published: September 2015

Objectives/Hypothesis

Gabapentin and pregabalin are useful for treating neuropathic pain because of their antiallodynic and antihyperalgesic properties, which may be beneficial in managing acute postoperative pain. The goal of this meta‐analysis was to perform a systematic review of the literature on the effect of gabapentinoids on postoperative pain following tonsillectomy, and its adverse effects in patients.

Data Sources: MEDLINE, SCOPUS, and Cochrane database.

Methods

Two authors independently searched the databases from their inception of article collection to May 2015. Included in the analysis were studies that compared preoperative gabapentinoid administration (gabapentinoids groups) with a placebo or pain control agent (control group) during a 24‐hour postoperative period, the outcomes of interest being postoperative pain intensity; rescue analgesic consumption; or adverse effects such as sedation, nausea and vomiting, dizziness, and headache.

Results

The pain score reported by the physician during the first 8 hours, as well as the need for analgesics during 24 hours postoperatively, were significantly decreased in the gabapentinoids group versus the control group. Additionally, there was no significant difference between gabapentinoids and control groups for adverse effect during 24 hours postoperatively. In the subgroup analyses (gabapentin and pregabalin) regarding pain‐related measurements, two subgroups showed the similar effect on reducing the postoperative pain severity.

Conclusion

Preoperative administration of gabapentinoids could provide pain relief without side effects in patients undergoing tonsillectomy. However, considering the insufficient evaluation of efficacy of gabapentinoids according to the high heterogeneity in some parameters, further clinical trials with robust research methodology should be conducted in order to confirm the results of this study.

Level of Evidence

NA. Laryngoscope, 126:357–366, 2016
Epley and Semont maneuvers for posterior canal benign paroxysmal positional vertigo: A network meta‐analysis
Authors: Liu Yun , Wang Wei , Zhang Ao‐bo , Bai Xue , Zhang Shuang
Published: September 2015

Objectives/Hypothesis

Using network meta‐analysis, we aimed to compare the efficacy and safety of Epley and Semont maneuvers as treatment options for posterior canal benign paroxysmal positional vertigo.

Study Design

Network meta‐analysis.

Methods

Randomized controlled studies with a Jadad score ≥ 3 that used an Epley or Semont maneuver in posterior canal benign paroxysmal positional vertigo patients were analyzed in this project. The following efficacy outcomes included 1‐week recovery rate and end of study recovery rate. Recurrence rate was used to assess the safety of each treatment.

Results

Of 589 articles, 12 studies that enrolled 999 posterior canal benign paroxysmal positional vertigo patients were selected. The pooled analysis revealed that the Epley maneuver was as efficacious as the Semont maneuver, in both the 1‐week recovery rate and end of study recovery rate (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 0.48‐7.00; OR = 1.8, 95% CI = 0.47‐7.20), and had a similar recurrence rate (OR = 1.00, 95% CI = 0.33‐4.4). These two techniques were both better than sham‐controlled treatment in the two efficacy indicators. No difference was observed in recurrence rate for treatments.

Conclusions

The Epley maneuver was similar to the Semont maneuver in both efficacy and safety for posterior canal benign paroxysmal positional vertigo in short‐term effects, and both were superior to the sham‐controlled treatment.

Level of Evidence

NA Laryngoscope, 126:951–955, 2016
WACODI: A generic algorithm to derive the intrinsic color of natural waters from digital images
Authors: Novoa Stéfani , Wernand Marcel , van der Woerd Hendrik Jan
Published: September 2015

This document presents the WAter COlor from Digital Images (WACODI) algorithm, which extracts the color of natural waters from images collected by low‐cost digital cameras, in the context of participatory science and water quality monitoring. SRGB images are converted to the CIE XYZ color space, undergoing a gamma expansion and illumination correction that includes the specular reflection at the air‐water interface. The XYZ values obtained for each pixel of the image are converted to chromaticity coordinates and Hue color angle (αw), which is a measure of color. Based on the distributions of αw in sub‐sections of the image, an approximation of the intrinsic color of the water is obtained. This algorithm was applied to images acquired in 2013 during two field campaigns in Northern Europe. The Hue color angles were derived from hyperspectral measurements above and below the surface, carried out simultaneously with image acquisition. When for each station a specific illumination correction was applied, based on the corresponding hyperspectral data, a good fit (r2 = 0.93) was obtained between the image and the spectra Hue color angles (slope = 0.98, intercept = −0.03). When a more generic illumination correction was applied to the same images, based on the sky conditions at the time of the image acquisition (either overcast or sunny), a slightly inferior, but still satisfactory fit resulted. Results on the application of the WACODI algorithm to the first images collected by the public via the smartphone application or “APP,” developed within the European FP7 Citclops, are presented at the end of this study.
Conference Tutorials as Educational Tool in Polymer Science: The POLYCHAR Conference and Short Course
Authors: Hess Michael
Published: September 2015

Tutorials in combination with a scientific conference are very useful tools in the education of advanced students, young scientists and newcomers in polymer science. The annual POLYCHAR Conference (World Forum for Advanced Materials) and its Short Course in Polymer Characterization are presented and discussed as an example of a successful combination.
Clinical features of patients with Myasthenia gravis from the Henan province, China
Authors: Gao Feng , Zhao Xue , Zhang Jing , Cui Xinzheng , Zhang Yingna , Li Qianru , Liu Pingping , Fang Hua , Du Ying , Zhang Qingyong , Yang Junhong , Zhang Yunke
Published: September 2015

Introduction

Myasthenia gravis (MG) occurs globally, and many studies have indicated that there are regional differences in epidemiology, biomarkers, and prognosis of MG.

Methods

A total of 478 patients with MG who visited hospitals in the Henan Province between January 2010 and February 2014 were included. Age, gender, age at onset, serum antibody, thymus pathology, treatment information, and Myasthenia Gravis Foundation of America (MGFA) classification were assessed.

Results

Compared with previous reports from other areas, we found some differences in MG patients from Henan. The proportion of childhood MG in our study was lower than other reports of Oriental patients with MG. There seems to be an association between onset age, muscle involvement, and acetylcholine receptor antibody levels. Thymectomy improved the symptoms in 78.5% of thymectomy‐treated patients.

Conclusions

These differences are likely related to geographical, environmental, and ethnic differences. Understanding these differences will help us to define more specific treatment. Muscle Nerve 53: 711–716, 2016
Formation of Pickering emulsion by use of PCM and SiC and application to preparation of hybrid microcapsules with interfacial polycondensation reaction
Authors: Taguchi Yoshinari , Morita Ryohei , Saito Natukaze , Tanaka Masato
Published: September 2015

It was tried to form Pickering emulsion by use of paraffin wax as a phase change material (PCM) and SiC as solid powder and to apply to the preparation of the hybrid microcapsules with the interfacial polycondensation reaction. Pickering emulsion could be formed by stirring PCM and SiC in the continuous water phase. The mean diameter of PCM droplets in the (O/W) emulsion decreased with the added amount of SiC. The SiC weight adhered on the surface of PCM droplets become the maximum in the continuous phase with pH 6.8. The hybrid microcapsules with the shell made of SiC and polyurea resin film could be prepared by using Pickering emulsion. There was a critical adhesion weight of SiC, above which the hybrid microcapsules could not be formed. Thermal conductivity of hybrid microcapsules could be improved as compared with the PCM microcapsules. Copyright © 2015 John Wiley & Sons, Ltd.
Neprilysin Inhibition in Heart Failure with Reduced Ejection Fraction: A Clinical Review
Authors: King Jordan B. , Bress Adam P. , Reese Austin D. , Munger Mark A.
Published: September 2015

There has been a 10‐year hiatus in the approval of a new pharmacotherapy for patients with chronic heart failure with a reduced ejection fraction (HFrEF). Combining an angiotensin receptor blocker, valsartan, with sacubitril, an inhibitor of neprilysin, results in increasing levels of natriuretic peptides that counterbalance high circulating levels of neurohormones in HFrEF. This has resulted in the development of a new agent, LCZ696. A comprehensive overview of LCZ696, its pharmacology, its role in the pathophysiology of HFrEF, completed and future clinical trial information, specific critical issues, and the place of LCZ696 in HFrEF therapy are presented.
Pharmacokinetic and Pharmacodynamic Properties of Oral Voriconazole in Patients with Invasive Fungal Infections
Authors: Wang Taotao , Xie Jiao , Wang Yan , Zheng Xiaowei , Lei Jin'e , Wang Xue , Dong Haiyan , Yang Qianting , Chen Limei , Xing Jianfeng , Dong Yalin
Published: September 2015

Study Objectives

To assess the pharmacokinetic and pharmacodynamic (PK/PD) properties of voriconazole and to investigate the relationship between PK/PD parameters and the efficacy of a fixed‐dose oral regimen in the treatment of invasive fungal infections (IFIs).

Design

Prospective and observational PK/PD study.

Setting

A university‐affiliated medical center.

Patients

Fifteen hospitalized patients with proven IFIs who were treated with oral voriconazole for at least 2 weeks.

Methods

We investigated the PK/PD properties of voriconazole using a noncompartmental analysis in 15 patients.

Results

Marked interpatient variation in voriconazole pharmacokinetic properties was noted including peak plasma concentrations (median 2.31 mg/L, range 1.06–4.01 mg/L), 12‐hour area under the plasma concentration‐time curve (AUCτ) (median 21.18 hr mg/L, range 7.71–42.07 hr mg/L), ratio of the unbound drug AUC over 24 hours (fAUC24) divided by the minimum inhibitory concentration (fAUC24:MIC; median 62.61, range 6.48–415.30), and the free trough plasma concentration (Cmin) divided by the MIC (fCmin:MIC; median 1.81, range 0.46–15.52). There was a good correlation between voriconazole Cmin and AUCτ (R2 = 0.805). Voriconazole therapy was effective in 66.7% of patients (10/15). No significant difference was observed with regard to successful clinical response between the patients with a fAUC24:MIC and fCmin:MIC values higher than 25 and higher than 1 (10/12 vs 10/13, respectively; χ2 = 1.61, p=0.688).

Conclusion

There is substantial interpatient variability in the PK/PD properties of voriconazole. fAUC24:MIC values higher than 25 and fCmin:MIC values higher than 1 may predict clinical response in patients with IFIs. Designing an optimal dosage regimen based on individual PK/PD properties will improve the efficacy in patients with IFIs.
Atomoxetine for Orthostatic Hypotension in an Elderly Patient Over 10 Weeks: A Case Report
Authors: Hale Genevieve M. , Brenner Michael
Published: September 2015

Several nonpharmacologic strategies for orthostatic hypotension exist including avoiding large carbohydrate‐rich meals; limiting alcohol consumption; maintaining adequate hydration; adding salt to foods; and using compression stockings, tilt‐table exercises, or abdominal binders. If these fail, however, only limited evidence‐based pharmacologic treatment options are available including the use of fludrocortisone, midodrine, pyridostigmine, and droxidopa as well as pseudoephedrine, ocetreotide, and atomoxetine. This report discusses a case of atomoxetine use for 10 weeks in an elderly patient with primary orthostatic hypotension. An 84‐year‐old man with long‐standing primary orthostatic hypotension presented to our ambulatory cardiology pharmacotherapy clinic after several unsuccessful pharmacologic therapies including fludrocortisone, midodrine, and pyridostigmine. Nonpharmacologic strategies were also implemented. Atomoxetine was initiated, and the patient showed gradual improvements in symptoms and blood pressure control over the course of 10 weeks. Our data suggest that low‐dose atomoxetine is an effective and safe agent for symptom improvement and blood pressure control in elderly patients with primary orthostatic hypotension.
Rational design of methacrylate monomers containing oxadiazole moieties for single‐layer organic light emitting devices
Authors: Zdyrko Bogdan , Bandera Yuriy , Tsyalkovsky Volodymyr , Huebner Christopher F. , Shetzline Jamie A. , Rungta Parul , Roeder Ryan D. , Tonkin Charles , Creager Stephen E. , Foulger Stephen H.
Published: September 2015

Methacrylate derived monomers functionalized with pendant oxadiazole moieties were synthesized and copolymerized with carbazole containing monomers to form polymers with electron and hole transporting fragments in the same molecule. Substituents on the oxidazole moiety were varied with the purpose of bandgap tuning and performance optimization when employed in single‐layer organic light emitting devices (OLED). Quantum mechanical calculations of the HOMO‐LUMO levels of the oxidazole derivatives were used to down‐select promising candidates for chemical synthesis and testing in single‐layer OLEDs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015, 53, 1663–1673
The impact of surgery for vulval cancer upon health‐related quality of life and pelvic floor outcomes during the first year of treatment: a longitudinal, mixed methods study
Authors: Jones Georgina L. , Jacques Richard M. , Thompson Joanne , Wood Hilary J. , Hughes Jane , Ledger William , Alazzam Mo'iad. , Radley Stephen C. , Tidy John A.
Published: September 2015

Objective

To measure the long‐term impact of surgical treatment for vulval cancer upon health‐related quality of life and pelvic floor outcomes during the first year of therapy.

Methods

Prospective, longitudinal, mixed‐methods study. Twenty‐three women aged >18 years with a new diagnosis of vulval cancer were recruited. The EORTC QLQ C30, SF‐36 and an electronic pelvic floor assessment questionnaire (ePAQ‐PF) were administered at baseline (pre‐treatment) and 3, 6, 9 and 12 months post‐treatment. Mixed effects repeated measures models (all adjusted for age and BMI) were used to investigate changes over time and differences between cancer stage. Qualitative interviews were carried out with 11 of the women and analysed using a thematic approach.

Results

Mean age was 59.9 years (SD = 15.3; range = 23.8–86.6 yrs). Mean BMI was 30.0 (SD = 4.5; range = 24.4–38.2). Sixteen women had early (Stage 1 to 2B), and seven women had advanced stage disease (Stage 3 to 4B). Questionnaire scores revealed that physical and social functioning, fatigue, pain and general sex life were significantly worse at 12 months than pre‐treatment (p = < 0.05). Qualitative analysis revealed multiple treatment side effects which were perceived as severe and enduring. Women with advanced vulval cancer had significantly worse SF‐36 mental health scores at 12 months compared to women with early stage disease (p = 0.037).

Conclusions

Surgery for vulval cancer has long‐term implications which can be persistent 12 months post‐treatment. High rates of morbidity relating to lymphoedema and sexual function re‐enforce the need for specialist clinics to support women who suffer these complications. © 2015 The Authors. Psycho‐Oncology published by John Wiley & Sons Ltd.
Let's talk about sex after cancer: exploring barriers and facilitators to sexual communication in male cancer survivors
Authors: Seidler Zac E. , Lawsin Catalina R. , Hoyt Michael A. , Dobinson Katherine A.
Published: September 2015

Objective

Changes to sexuality are a primary concern amongst cancer survivors, leading to psychological distress and impacting long‐term quality of life. Effective sexual communication has been found to be critical in improving sexual satisfaction post‐treatment. However, research suggests that many men struggle to disclose sexual concerns and preferences. This study aimed to qualitatively explore the common barriers and facilitators to sexual communication in male cancer survivors (MCSs).

Methods

Seventeen MCSs participated in semi‐structured telephone interviews, which were transcribed and coded using Grounded Theory methodology.

Results

The emergent theory described that those MCSs with lower quality sexual communication experienced diminished perceived masculinity following cancer‐related sexual dysfunction. These feelings of inadequacy were compounded by inadequate partner support. Contrastingly, participants reporting effective sexual communication expressed the importance of a stable self‐esteem and flexible partner support.

Conclusions

This study challenges the notion that men naturally struggle with intimate dyadic communication and suggests that adequate partner support and a stable sense of self can mitigate MCSs' communicative behaviour, subsequently bolstering self‐esteem. Future research should more broadly explore the diverse experiences of MCSs to enhance the efficacy of psychosexual interventions. Copyright © 2015 John Wiley & Sons, Ltd.
Preparation and Properties of Boron‐Based Nano‐B/NiO Thermite
Authors: Liu Ting , Chen Xin , Xu Huixiang , Han Aijun , Ye Mingquan , Pan Gongpei
Published: September 2015

Boron particles have several major burning problems, such as incomplete combustion, poor ignitability, and a complex burning process in solid propellants. It is documented that the low ignitability and combustion efficiency of boron are caused by the oxidation of its surface. In order to improve the combustion efficiency of boron particles, a precipitation method was employed to prepare nanometer‐sized NiO and coat it on boron particles. The morphology and coating results of the B/NiO nanocomposite thermite were characterized using different approaches such as SEM, X‐ray Diffraction (XRD), and EDS. The results indicated that the boron particles were well distributed and coated completely by nanocomposite NiO. The B/NiO nanocomposite thermite reaction process was tested by TG‐DTA. The results showed that the reaction temperature of B/NiO particles is about 30 °C lower than that of boron particles. The B/NiO thermite and boron powder were added to Mg/PTFE propellant to be measured for their respective combustion performance. The results showed that the burning rate of the B/NiO‐Mg/PTFE propellant increased by 22.8–25.2 %, mass burning rate by 26.7–30.8 %, and combustion temperature increased by 8–56 °C compared to the B‐Mg/PTFE propellant. The above results indicate that NiO coating of boron particles has a significant effect on the combustion behavior and increases the combustion performance of the propellant compared with uncoated particles.
Thermal recovery process of electron irradiated Si1‐xCx source/drain n‐MOSFETs
Authors: Takakura Kenichiro , Hori Masato , Yoneoka Masashi , Tsunoda Isao , Nakashima Toshiyuki , Simoen Eddy , Claeys Cor
Published: September 2015

In this study, the performance degradation by electron irradiation and the thermal recovery process of Si0.99C0.01 source/drain (S/D) n‐MOSFETs are reported. The electron mobility is 15% enhanced by 1%‐C doping in the S/D stressor region. The electron mobility is degraded by 2‐MeV electron irradiation, but the relative change was the same irrespective of C doping and electron fluence. This fact indicates that tensile‐strain relaxation by displacement damage in the Si:C stressors is not significantly impacting the mobility degradation by electron irradiation. Evidence is given that increased scattering in the channel is the main cause of mobility degradation by 2‐MeV electron irradiation. In addition, it is shown that for a fluence of 5x1017 e/cm2, the electrical performance is recovered by thermal annealing. After 323 K for 15 min annealing, the mobility amounts to 95% of the pre‐irradiation value. In the case of Si0.7Ge0.3 S/D p‐MOSFETs, it has been shown before that the device performance is recovered to the same degree for the same irradiation/thermal annealing conditions of this study. CMOS circuits are fabricated by a combination of n‐MOSFETs and p‐MOSFETs, therefore, it can be confirmed that strained CMOS devices using Si:C S/D n‐MOSFETs and SiGe S/D p‐MOSFETs, respectively, can operate in the radiation environment studied here. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Stably stratified airflow over a waved water surface. Part 1: Stationary turbulence regime
Authors: Druzhinin O. A. , Troitskaya Y. I. , Zilitinkevich S. S.
Published: September 2015

Stably stratified turbulent boundary‐layer flows over both a waved water surface and a flat smooth surface are investigated through direct numerical simulation (DNS) for the bulk Reynolds numbers, Re, from 15000 to 80000. DNS expose the following basic properties of the flow. A statistically stationary turbulent regime is sustained if the turbulent Reynolds number, ReL, based on the Obukhov length‐scale and friction velocity, is larger than 102. At ReL < 102, turbulence over a flat surface degenerates completely, but over a waved surface it survives in the form of residual fluctuations, which are weaker for smaller wave slopes. In the stationary turbulent regime, at ReL > 102, vertical profiles of the mean‐flow velocity and temperature have a log‐linear shape, as predicted by the Monin‐Obukhov similarity theory, with the same empirical dimensionless constants as in laboratory and field experiments. The velocity and temperature roughness lengths, vertical turbulent fluxes of momentum and heat, and root mean square turbulent velocity and temperature fluctuations increase with increasing slope of the surface waves. At the same time, vertical profiles of the mean velocity and temperature keep the self‐similar shape predicted by the Monin–Obukhov theory, irrespective of the wave slope.
Impacts of orography and rain intensity on rainfall structure. The case of the HyMeX IOP7a event
Authors: Zwiebel J. , Van Baelen J. , Anquetin S. , Pointin Y. , Boudevillain B.
Published: September 2015

The first Special Observation Period of the HyMeX campaign took place during autumn 2012. A specific observational network was set up in the south of France with the aim of better understanding the role and impact of complex terrain on the horizontal and vertical structure of rainfall and the associated microphysical processes. The event, referred to as IOP7a, which occurred on 26 September 2012, is studied in this article. A first analysis, based on two reference parameters of the drop‐size distribution (DSD), shows that the topography of the region has an impact on the rainfall structure at the fine scale and that rainfall intensity also has an influence on the DSD parameters. A more detailed study, based on the evolution of the shape of the DSD and of the liquid water content (LWC) within different rainfall intensities, reveals that the coalescence mechanism is of significant importance for different rainfall regimes and for different topographic areas. As we get closer to the ground, the modification of the DSD shows that other microphysical and dynamical processes (such as evaporation, break‐up, turbulence in the presence of vertical wind) might compete with the coalescence mechanism or enhance it. The respective strengths of these processes depend on the local environment; coalescence seems enhanced by a layer with higher LWC as the local terrain becomes more complex, and evaporation appears more important above flatter terrain. Thus, both the orography and the rainfall intensity can impact the rainfall structure and the associated microphysical and dynamical processes.
Data storytelling
Authors: Heeg Robert
Published: September 2015

Presenting data to audiences does not have to be a mind‐numbing PowerPoint affair.
Research: Provider of, or in need of, revelation?
Authors: Raben Finn
Published: September 2015

Will research continue to be perceived as an essential contributor to the success of the business?
Rheology, morphology, and mechanical properties of reactive compatibilized polypropylene/polystyrene blends via Friedel–Crafts alkylation reaction in the presence of clay
Authors: Abbasi Fatemeh , Tavakoli Akram , Razavi Aghjeh Mir Karim
Published: September 2015

Attempts were made to study the effect of reactive compatibilization via Friedel–Crafts alkylation reaction, using AlCl3 as a catalyst, on rheology, morphology, and mechanical properties of polypropylene/polystyrene (PP/PS) blends in the presence of an organoclay (Cloisite 15A). During the reactive compatibilization process, PS showed much more degradation than that of PP in the presence of AlCl3. It was found that the effect of generation of PP‐g‐PS copolymer at the interface of the PP/PS blend dominates the effects of degradation of PS and PP phases, which manifested itself by increased toughness as well as uniform dispersion of the dispersed PS particles in the PP matrix. Generation of PP‐g‐PS copolymer was confirmed by using Fourier‐transform infrared analysis. By using rheological and X‐ray diffraction analyses, it was shown that the clay had higher affinity to PS than that of PP. It was also shown that the clay located at the interface of PP and PS phases, leading to increased relaxation time of the deformed PS dispersed particles, exhibited higher dispersion in PP/PS blend, which resulted in higher ductility of the blend. By using the results of rheological studies, it was concluded that during reactive compatibilization of the blend nanocomposite, the clay migrated into the dispersed PS phase, which was confirmed by scanning electron microscopy analysis. It was demonstrated that the rheological studies have a reliable sensitivity to the clay partitioning and phase morphology of the studied blends and blend nanocomposites. J. VINYL ADDIT. TECHNOL., 24:18–26, 2018. © 2015 Society of Plastics Engineers
Communicating climate change: conduits, content, and consensus
Authors: Pearce Warren , Brown Brian , Nerlich Brigitte , Koteyko Nelya
Published: September 2015

Climate change has been the subject of increasing efforts by scientists to understand its causes and implications; it has been of growing interest to policymakers, international bodies, and a variety of nongovernment organizations; and it has attracted varied amounts of attention from traditional and, increasingly, online media. These developments have been aligned with shifts in the nature of climate change communication, with changes in how researchers study it and how a variety of actors try to influence it. This article situates the theory and practice of climate change communication within developments that have taken place since we first reviewed the field in 2009. These include the rise of new social media conduits for communication, research, and practice aimed at fine tuning communication content, and the rise to prominence of scientific consensus as part of that content. We focus in particular on continuing tensions between a focus on the part of communicators to inform the public and more dialogic strategies of public engagement. We also consider the tension between efforts to promote consensus and certainty in climate science and approaches that attempt to engage with uncertainty more fully. We explore the lessons to be learnt from climate communication since 2009, highlighting how the field remains haunted by the deficit model of science communication. Finally, we point to more fruitful future directions for climate change communication, including more participatory models that acknowledge, rather than ignore, residual uncertainties in climate science in order to stimulate debate and deliberation. WIREs Clim Change 2015, 6:613–626. doi: 10.1002/wcc.366

This article is categorized under:

Perceptions, Behavior, and Communication of Climate Change > Communication