bluuebunny/crossref_metadata_2025 huggingface dataset:
Using TextEvaluator® to Quantify Sources of Linguistic Complexity in Textbooks Targeted at First‐Grade Readers Over the Past Half Century
Authors: Sheehan Kathleen M. , Flor Michael , Napolitano Diane , Ramineni Chaitanya
Published: December 2015

This paper considers whether the sources of linguistic complexity presented within texts targeted at 1st‐grade readers have increased, decreased, or held steady over the 52‐year period from 1962 to 2013. A collection of more than 450 texts is examined. All texts were selected from Grade 1 textbooks published by Scott Foresman during the targeted time period. Analyses are implemented using the TextEvaluator® tool, a comprehensive text complexity evaluation tool designed to help teachers, textbook publishers, and test developers identify and quantify text‐based sources of comprehension difficulty within informational, literary, and mixed texts. Results suggest that 1st‐grade textbooks published over the past half century have included an increasing proportion of informational passages, and this shift has been accompanied by the following specific changes: (a) an increase in the proportion of words that tend to appear less frequently in printed text, (b) an increase in the proportion of words that are more characteristic of academic text as opposed to fiction or conversation, (c) lower levels of referential cohesion, (d) lower levels of narrativity, and (e) fewer instances of an interactive/conversational style. These findings suggest that, in contrast to the claim of a “general, steady decline” in textbook complexity, text‐based sources of comprehension difficulty within Grade 1 texts have either risen or held steady throughout the past half century.
The Prospects for Biogas Integration with Fuel Cells in the United Kingdom
Authors: Torija S. , Castillo‐Castillo A. , Brandon N. P.
Published: December 2015

Anaerobic digestion (AD) presence is emerging in the UK because it has numerous environmental benefits as a waste management strategy and produces valuable biogas. This work shows that up to 5.5% of UK primary energy could be met by biogas, representing 14.4% of gas consumption. Fuel cells (FCs) are the most efficient and environmentally benign energy convertor of any device of equivalent scale and in addition are well suited for biogas utilization, which has worldwide led to the emergence of numerous integrated commercial applications. Thus, biogas coupling with fuel cells is proposed as a unique and virtuous AD scheme. A techno‐economic model has been developed for the two types of AD plants with the highest development prospects in the UK, namely livestock and food waste plants, whose performance and feasibility at different scales are scrutinized under several policy scenarios, some of which incorporate supportive mechanisms for the introduction of FCs. Results confirm that conventional AD projects can already be profitable in the current market environment, while projects involving FCs proved environmentally superior, virtually suppressing harmful pollutant emissions and decreasing the CO2emissions from using grid electricity and natural gas, at a reasonable avoided carbon cost in the best suited cases.
Ewing sarcoma with ERG gene rearrangements: A molecular study focusing on the prevalence of FUS‐ERG and common pitfalls in detecting EWSR1‐ERG fusions by FISH
Authors: Chen Sonja , Deniz Kemal , Sung Yun‐Shao , Zhang Lei , Dry Sarah , Antonescu Cristina R.
Published: December 2015

The genetics of Ewing sarcoma (ES) are characterized by a canonical fusion involving EWSR1 gene and a member of the ETS family of transcription factors, such as FLI1 and ERG. In fact, ERG gene rearrangements represent the second most common molecular alteration, with EWSR1‐ERG being identified in 5–10% of cases, while only a handful of reports document a FUS‐ERG fusion. In this study, we focus on ES with ERG gene abnormalities, specifically to investigate the prevalence and clinicopathologic features of FUS‐ERG fusions in a large cohort of small blue round cell tumors (SBRCTs) and compare to the eight reported FUS‐positive ES. Among the 85 SBRCTs tested, seven (8.2%) cases harbored FUS gene rearrangements; six fused to ERG and one with FEV. During this investigation we came across a number of ERG‐rearranged ES lacking both EWSR1 and FUS abnormalities by FISH. In one case, RNA sequencing identified an EWSR1‐ERG transcript despite the negative EWSR1 rearrangements by FISH. Additional 3‐color FISH fusion assay demonstrated the fusion of EWSR1 and ERG signals in all four cases negative for break‐apart EWSR1 FISH. These results emphasize a potential pitfall of relying on EWSR1 FISH assay alone for diagnosis of ES. In cases with classic morphology and/or strong CD99 and ERG immunoreactivity, additional molecular testing should be applied, such as ERG FISH or RT‐PCR/next generation sequencing, for a more definitive diagnosis. Although our study group is small, there were no differences noted between the clinical, morphologic features and immunoprofile of the different subsets of ERG‐rearranged SBRCTs. © 2015 Wiley Periodicals, Inc.
Minimizing revision rates with the “Π” technique for bilateral vocal fold immobility: A new technique combining carbon dioxide and diode laser
Authors: Karkos Petros D. , Stavrakas Marios
Published: December 2015

Background

For more than 25 years, posterior laser transverse cordotomy has been generally considered the ideal endoscopic minimally invasive procedure of choice for bilateral vocal fold immobility. The main drawback of this procedure, when compared to more aggressive “glottic aperture improvement” operations, is the high revision rates, caused by granulations, adhesion, and scar, for example.

Methods

We describe a technique using a combination of conventional and flexible lasers. Our technique seems to minimize the revision rates.

Conclusion

This new technique combining CO2 and diode laser is a safe alternative for treating bilateral vocal fold palsies. © 2015 Wiley Periodicals, Inc. Head Neck 38: 801–803, 2016
The exponential decline in saturated hydraulic conductivity with depth: a novel method for exploring its effect on water flow paths and transit time distribution
Authors: Ameli A. A. , McDonnell J. J. , Bishop K.
Published: December 2015

The strong vertical gradient in soil and subsoil saturated hydraulic conductivity is characteristic feature of the hydrology of catchments. Despite the potential importance of these strong gradients, they have proven difficult to model using robust physically based schemes. This has hampered the testing of hypotheses about the implications of such vertical gradients for subsurface flow paths, residence times and transit time distribution. Here we present a general semi‐analytical solution for the simulation of 2D steady‐state saturated‐unsaturated flow in hillslopes with saturated hydraulic conductivity that declines exponentially with depth. The grid‐free solution satisfies mass balance exactly over the entire saturated and unsaturated zones. The new method provides continuous solutions for head, flow and velocity in both saturated and unsaturated zones without any interpolation process as is common in discrete numerical schemes. This solution efficiently generates flow pathlines and transit time distributions in hillslopes with the assumption of depth‐varying saturated hydraulic conductivity. The model outputs reveal the pronounced effect that changing the strength of the exponential decline in saturated hydraulic conductivity has on the flow pathlines, residence time and transit time distribution. This new steady‐state model may be useful to others for posing hypotheses about how different depth functions for hydraulic conductivity influence catchment hydrological response. Copyright © 2016 John Wiley & Sons, Ltd.
Long‐term administration of a Niemann‐Pick C1‐like 1 inhibitor, ezetimibe, does not worsen bile lithogenicity in dyslipidemic patients with hepatobiliary diseases
Authors: Kishikawa Nobusuke , Kanno Keishi , Sugiyama Akiko , Yokobayashi Kenichi , Mizooka Masafumi , Tazuma Susumu
Published: December 2015

Background

Certain lipid‐lowering drugs increase bile lithogenicity. Here we investigated whether long‐term administration of ezetimibe, a new class of hypocholesterolemic agents designed to inhibit intestinal cholesterol absorption by inhibiting Niemann‐Pick C1‐like 1, alters bile lithogenicity in patients with hepatobiliary diseases.

Methods

Eleven dyslipidemic patients with gallstones and/or fatty liver diseases were treated with ezetimibe (10 mg/day) for 12 months. Bile samples were collected by nasal endoscopy before and after 3 and 12 months of treatment. Serum and bile lipids and serum metabolic parameters were analyzed.

Results

Serum levels of campesterol, total cholesterol, and low‐density lipoprotein cholesterol were significantly decreased after 3 and 12 months of treatment. In contrast, serum lathosterol levels increased gradually. The lithogenic index of bile was unsaturated and unchanged in patients who were previously and concomitantly receiving ursodeoxycholic acid (UDCA). In patients who were not receiving UDCA, bile was initially supersaturated, but eventually was unsaturated. However, ezetimibe tended to elevate bile lithogenicity in cholecystectomy patients.

Conclusions

Long‐term treatment with ezetimibe improves lipid metabolism without significantly altering the bile lithogenicity. Therefore, inhibiting intestinal cholesterol absorption in dyslipidemic patients with hepatobiliary diseases is a safe therapeutic strategy without worsening biliary physiology.
Systematic review and meta‐analysis of the accuracy of MRI to diagnose appendicitis in the general population
Authors: Repplinger Michael D. , Levy Joseph F. , Peethumnongsin Erica , Gussick Megan E. , Svenson James E. , Golden Sean K. , Ehlenbach William J. , Westergaard Ryan P. , Reeder Scott B. , Vanness David J.
Published: December 2015

Purpose

To perform a systematic review and meta‐analysis of all published studies since 2005 that evaluate the accuracy of magnetic resonance imaging (MRI) for the diagnosis of acute appendicitis in the general population presenting to emergency departments.

Materials and Methods

All retrospective and prospective studies evaluating the accuracy of MRI to diagnose appendicitis published in English and listed in PubMed, Web of Science, Cinahl Plus, and the Cochrane Library since 2005 were included. Excluded studies were those without an explicitly stated reference standard, with insufficient data to calculate the study outcomes, or if the population enrolled was limited to pregnant women or children. Data were abstracted by one investigator and confirmed by another. Data included the number of true positives, true negatives, false positives, false negatives, number of equivocal cases, type of MRI scanner, type of MRI sequence, and demographic data including study setting and gender distribution. Summary test characteristics were calculated. Forest plots and a summary receiver operator characteristic plot were generated.

Results

Ten studies met eligibility criteria, representing patients from seven countries. Nine were prospective and two were multicenter studies. A total of 838 subjects were enrolled; 406 (48%) were women. All studies routinely used unenhanced MR images, although two used intravenous contrast‐enhancement and three used diffusion‐weighted imaging. Using a bivariate random‐effects model the summary sensitivity was 96.6% (95% confidence interval [CI]: 92.3%–98.5%) and summary specificity was 95.9% (95% CI: 89.4%–98.4%).

Conclusion

MRI has a high sensitivity and specificity for the diagnosis of appendicitis, similar to that reported previously for computed tomography. J. Magn. Reson. Imaging 2016;43:1346–1354.
Relationship betweenIFNA1,IFNA5,IFNA10, andIFNA17gene polymorphisms and Crimean‐Congo hemorrhagic fever prognosis in a Turkish population range
Authors: Elaldi Nazif , Yilmaz Meral , Bagci Binnur , Yelkovan Izzet , Bagci Gokhan , Gozel Mustafa Gokhan , Engin Aynur , Bakir Mehmet , Dokmetas Ilyas
Published: December 2015

Crimean‐Congo hemorrhagic fever (CCHF) is a fatal emerging acute viral infection. Not much is known regarding the pathogenic mechanisms and the reasons behind severe or mild disease courses in CCHF. IFN‐alpha (IFNA) is one of the essential cytokines in the immune system. Existence of single nucleotide gene polymorphisms (SNPs) in cytokines can cause susceptibility or resistance to viral agents and different clinical courses. Hence, the relationship between SNPs in genes encoding cytokines (IFNA1‐1823G/A (rs1332190),IFNA5‐2529T/A (rs758236),IFNA10Cys20stop (rs10119910), andIFNA17Ile184Arg (rs9298814) SNPs and disease susceptibility were investigated. The associations between SNPs and CCHF prognosis were also studied. Total 150 patients with CCHF and 170 healthy individuals were enrolled. Genotyping was performed by PCR‐RFLP methods. The frequency ofIFNA1‐1823 (rs1332190) GG genotype was significantly higher in control subjects than CCHF patients (20% vs. 8%;P = 0.01). ForIFNA17Ile184Arg (rs9298814) polymorphism, CCHF patients having TG genotype had a higher frequency than the control subjects (38% vs. 32.4%;P = 0.039). The distribution of TT + TG genotype frequencies was also significantly higher in CCHF group than the controls (97.3% vs. 91.8%;P = 0.049). Genotype and allele frequencies for IFNA subtypes between fatal and survivors were the same (P > 0.05). Genotype and allele frequencies between severe and mild/moderate CCHF patients were also the same (P > 0.05). The results show thatIFNA1rs1332190 andIFNA17rs9298814 SNPs may play an important role in CCHF susceptibility. Determining the existence of other connections for IFNA SNPs and CCHF severity and fatality requires further investigations.J. Med. Virol. 88:1159–1167, 2016. © 2015 Wiley Periodicals, Inc.
Long‐term trends in precipitation and temperature across the Caribbean
Authors: Jones Philip D. , Harpham Colin , Harris Ian , Goodess Clare M. , Burton Aidan , Centella‐Artola Abel , Taylor Michael A. , Bezanilla‐Morlot Arnoldo , Campbell Jayaka D. , Stephenson Tannecia S. , Joslyn Ottis , Nicholls Keith , Baur Timo
Published: December 2015

This study considers long‐term precipitation and temperature variability across the Caribbean using two gridded data sets (CRU TS 3.21 and GPCCv5). We look at trends across four different regions (Northern, Eastern, Southern and Western), for three different seasons (May to July, August to October and November to April) and for three different periods (1901–2012, 1951–2012 and 1979–2012). There are no century‐long trends in precipitation in either data set, although all regions (with the exception of the Northern Caribbean) show decade‐long periods of wetter or drier conditions. The most significant of these is for the Southern Caribbean region which was wetter than the 1961–1990 average from 1940 to 1956 and then drier from 1957 to 1965. Temperature in contrast shows statistically significant warming everywhere for the periods 1901–2012, 1951–2012 and for over half the area during 1979–2012. Data availability is a limiting issue over much of the region and we also discuss the reliability of the series we use in the context of what is known to be available in the CRU TS 3.21 data set. More station data have been collected but have either not been fully digitized yet or not made freely available both within and beyond the region.
Pilot‐scale radio frequency pasteurisation of chili powder: heating uniformity and heating model
Authors: Li Yukun , Zhang Yongdi , Lei Yujie , Fu Hongfei , Chen Xiangwei , Wang Yunyang
Published: December 2015

BACKGROUND

Microbial contamination is a vital obstacle needed to overcome for food safety of condiments. Radio frequency (RF) pasteurisation is a new technology to solve this obstacle. Temperature distribution and heating uniformity of sample, which are influenced by different factors, are the most important things affecting the nutritional ingredients and microbial safety of sample in the process of RF pasteurisation. This study demonstrated the location of cold spot in chili powder by analysing temperature distribution in horizontal and vertical direction. The related models were established and the accuracy was verified.

RESULTS

Cold spot located on the centre of sample surface in the process of RF pasteurisation. The averaged temperature of sample increased linearly. The uniformity index decreased as the averaged temperature increased. Both the correlation coefficient of two equations were greater than 0.91. The error value of heating rate and heating uniformity index was 0.54% and 0.75% between the measured value and predicted value.

CONCLUSION

Electric field was not uniformly distributed between RF parallel‐plate electrodes in the RF pasteurisation of chili powder. The heating models were reliable to predict experiment results with high precision and accuracy. © 2015 Society of Chemical Industry
Supraglottoplasty for laryngomalacia with obstructive sleep apnea: A systematic review and meta‐analysis
Authors: Camacho Macario , Dunn Brandyn , Torre Carlos , Sasaki Jodie , Gonzales Raymond , Liu Stanley Yung‐Chuan , Chan Dylan K. , Certal Victor , Cable Benjamin B.
Published: December 2015

Objectives/Hypothesis

To determine if apnea‐hypopnea index (AHI) and lowest oxygen saturation (LSAT) improve following isolated supraglottoplasty for laryngomalacia with obstructive sleep apnea (OSA) in children.

Study Design

Systematic review and meta‐analysis.

Methods

Nine databases, including PubMed/MEDLINE, were searched through September 30, 2015.

Results

A total of 517 studies were screened; 57 were reviewed; and 13 met criteria. One hundred thirty‐eight patients were included (age range: 1 month–12.6 years). Sixty‐four patients had sleep exclusive laryngomalacia, and in these patients: 1) AHI decreased from a mean (M) ± standard deviation (SD) of 14.0 ± 16.5 (95% confidence interval [CI] 10.0, 18.0) to 3.3 ± 4.0 (95% CI 2.4, 4.4) events/hour (relative reduction: 76.4% [95% CI 53.6, 106.4]); 2) LSAT improved from a M ± SD of 84.8 ± 8.4% (95% CI 82.8, 86.8) to 87.6 ± 4.4% (95% CI 86.6, 88.8); 3) standardized mean differences (SMD) demonstrated a small effect for LSAT and a large effect for AHI; and 4) cure (AHI < 1 event/hour) was 10.5% (19 patients with individual data). Seventy‐four patients had congenital laryngomalacia, and in these patients: 1) AHI decreased from a M ± SD of 20.4 ± 23.9 (95% CI 12.8, 28.0) to 4.0 ± 4.5 (95% CI 2.6, 5.4) events/hour (relative reduction: 80.4% [95% CI 46.6, 107.4]); 2) LSAT improved from a M ± SD of 74.5 ± 11.9% (95% CI 70.9, 78.1) to 88.4 ± 6.6% (95% CI 86.4, 90.4); 3) SMD demonstrated a large effect for both AHI and LSAT; and 4) cure was 26.5% (38 patients with individual data).

Conclusion

Supraglottoplasty has improved AHI and LSAT in children with OSA and either sleep exclusive laryngomalacia or congenital laryngomalacia; however, the majority of them are not cured. Laryngoscope, 126:1246–1255, 2016
Selective tissue ablation using laser radiation at 355 nm in lead extraction by a hybrid catheter; a preliminary report
Authors: Herzog Amir , Bogdan Stefan , Glikson Michael , Ishaaya Amiel Abraham , Love Charles
Published: December 2015

Background

Current lead extraction (LE) devices can harm the blood vessel endothelium, increasing the risk of perforation.

Objective

Proof of concept for using a solid‐state pulsed laser at 355 nm with a hybrid catheter in LE.

Methods

A hybrid catheter was used comprising optical fibers for the delivery of 355 nm laser pulses at 30 Hz and 6 J/cm2 combined with a blunt mechanical blade. Specific parameters were chosen to enable selectivity in ablation, thereby reducing the risk of blood vessel perforation. The design exploits differences in the mechanical properties of the fibrotic tissue and the normal blood vessel. Ex vivo ablation was performed to evaluate a hybrid catheter operation on various tissues. Two ex/in vivo pig studies used a free‐floating electrode to which three bovine tendon pieces were glued. Finally, two in vivo dog model studies were performed on specimens with 4‐5‐year‐old pacing lead implants, followed by a histopathology study.

Results

Catheter penetration rate in the ex vivo experiments was 0.1 mm/seconds for bovine tendon, 0.025 mm/seconds for porcine superior vena cava and 0.033 mm/seconds for porcine aorta. In the ex/in vivo pig study, the three tissue blocks were successfully dissected. In the in vivo dog study, the two leads were successfully extracted. In all in vivo tests, hemodynamic stability was maintained. Gross histopathology did not reveal any injury.

Conclusions

Ablation using 355 nm laser pulses in combination with a mechanical blunt blade may potentially constitute a viable alternative for LE. Lasers Surg. Med. 48:281–287, 2016. © 2015 Wiley Periodicals, Inc.
Solar Light Responsive Polymer Composites with Three Shape‐Memory Effects
Authors: Fang Liang , Fang Tianyu , Fang Zhenggang , Lu Chunhua , Xu Zhongzi
Published: December 2015

Solar light responsive polymer composites which can deform their shape according to the variation in sunlight power density are prepared by incorporating the solar light photothermal filler of Sm0.5Sr0.5CoO3 (SSC) into crosslinked poly[ethylene‐ran‐(vinyl acetate)] (EVA). Dual shape‐memory effect, temperature‐memory effect, and reversible bidirectional shape‐memory effect are all achieved in such EVA‐SSC composites. Dual shape‐memory effect with fixation ratio over 99% and recovery ratio over 95% is presented, while the responsive power density is adjusted from 0.4 to 0.1 w cm−2 by simply decreasing the programming temperature from 140 to 50 °C. Furthermore, during a cyclic variation in power density from 0 to 0.3 w cm−2 and back to 0 w cm−2 in 6 min, the composite specimens show a reversible angle deformation. Finally, a sunlight‐adaptive circuit switch is demonstrated using such composites, automatically turning off the LED lamp and turning on the motor fan according to the sunlight power density.

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Lysosomal alterations in peripheral blood mononuclear cells of Parkinson's disease patients
Authors: Papagiannakis Nikolaos , Xilouri Maria , Koros Christos , Stamelou Maria , Antonelou Roubina , Maniati Matina , Papadimitriou Dimitra , Moraitou Marina , Michelakakis Helen , Stefanis Leonidas
Published: December 2015

Background

Reduced expression of lysosomal‐associated membrane protein 2a and heatshock‐cognate 70 proteins, involved in chaperone‐mediated autophagy and of glucocerebrosidase, is reported in PD brains. The aim of this study was to identify systemic alterations in lysosomal‐associated membrane protein 2a, heatshock cognate‐70, and glucocerebrosidase levels/activity in peripheral blood mononuclear cells from PD patients.

Methods

Protein/mRNA levels were assessed in PD patients from genetically undetermined background, alpha‐synuclein (G209A/A53T), or glucocerebrosidase mutation carriers and age‐/sex‐matched controls.

Results

Heatshock cognate 70 protein levels were reduced in all PD groups, whereas its mRNA levels were decreased only in the genetically undetermined group. Glucocerebrosidase protein levels were decreased only in the genetic PD groups, whereas increased mRNA levels and decreased activity were detected only in the glucocerebrosidase mutation group.

Conclusions

Reduced heatshock cognate‐70 levels are suggestive of an apparent systemic chaperone‐mediated autophagy dysfunction irrespective of genetic background. Glucocerebrosidase activity may serve as a screening tool to identify glucocerebrosidase mutation carriers with PD. © 2015 International Parkinson and Movement Disorder Society
CISD1 in association with obesity‐associated dysfunctional adipogenesis in human visceral adipose tissue
Authors: Moreno‐Navarrete José María , Moreno María , Ortega Francisco , Sabater Mònica , Xifra Gemma , Ricart Wifredo , Fernández‐Real José Manuel
Published: December 2015

Objective

To investigate CISD1 mRNA and protein in human adipose tissue in association with obesity and adipogenesis.

Methods

Subcutaneous (SAT) and visceral (VAT) adipose tissue CISD1 gene expression (real‐time PCR) and protein (Western blot) levels were investigated in human adipose tissue and during human adipocyte differentiation.

Results

SAT and VAT CISD1 mRNA and protein levels were significantly decreased in subjects with obesity and negatively correlated with BMI after controlling for age and sex. In participants with morbid obesity, VAT CISD1 gene expression was positively correlated with insulin sensitivity (r = 0.47, P = 0.01), and bariatric surgery‐induced weight loss led to increased SAT CISD1 mRNA levels. In both VAT and SAT, CISD1 gene expression was significantly associated with SIRT1, ISCA2, and mitochondrial biogenesis‐related (PPARGC1A, TFAM, and MT‐CO3) and browning‐related (PRDM16 and UCP1) gene expression. In addition, VAT CISD1 gene expression was significantly associated with adipogenic and iron metabolism‐related genes. Importantly, these correlations were replicated in a second cohort. At the cellular level, CISD1 gene expression increased during human adipocyte differentiation in correlation with adipogenic genes (r > 0.60, P < 0.005).

Conclusions

These data suggest a possible role of CISD1 in obesity‐associated dysfunctional adipogenesis in human VAT.
HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials
Authors: Richman Susan D , Southward Katie , Chambers Philip , Cross Debra , Barrett Jennifer , Hemmings Gemma , Taylor Morag , Wood Henry , Hutchins Gordon , Foster Joseph M , Oumie Assa , Spink Karen G , Brown Sarah R , Jones Marc , Kerr David , Handley Kelly , Gray Richard , Seymour Matthew , Quirke Philip
Published: December 2015

HER2 overexpression/amplification is linked to trastuzumab response in breast/gastric cancers. One suggested anti‐EGFR resistance mechanism in colorectal cancer (CRC) is aberrant MEK–AKT pathway activation through HER2 up‐regulation. We assessed HER2‐amplification/overexpression in stage II–III and IV CRC patients, assessing relationships to KRAS/BRAF and outcome. Pathological material was obtained from 1914 patients in the QUASAR stage II–III trial and 1342 patients in stage IV trials (FOCUS and PICCOLO). Tissue microarrays were created for HER2 immunohistochemistry. HER2‐amplification was assessed using FISH and copy number variation. KRAS/BRAF mutation status was assessed by pyrosequencing. Progression‐free survival (PFS) and overall survival (OS) data were obtained for FOCUS/PICCOLO and recurrence and mortality for QUASAR; 29/1342 (2.2%) stage IV and 25/1914 (1.3%) stage II–III tumours showed HER2 protein overexpression. Of the HER2‐overexpressing cases, 27/28 (96.4%) stage IV tumours and 20/24 (83.3%) stage II–III tumours demonstrated HER2 amplification by FISH; 41/47 (87.2%) also showed copy number gains. HER2‐overexpression was associated with KRAS/BRAF wild‐type (WT) status at all stages: in 5.2% WT versus 1.0% mutated tumours (p < 0.0001) in stage IV and 2.1% versus 0.2% in stage II–III tumours (p = 0.01), respectively. HER2 was not associated with OS or PFS. At stage II–III, there was no significant correlation between HER2 overexpression and 5FU/FA response. A higher proportion of HER2‐overexpressing cases experienced recurrence, but the difference was not significant. HER2‐amplification/overexpression is identifiable by immunohistochemistry, occurring infrequently in stage II–III CRC, rising in stage IV and further in KRAS/BRAF WT tumours. The value of HER2‐targeted therapy in patients with HER2‐amplified CRC must be tested in a clinical trial. © 2015 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
FN1–EGF gene fusions are recurrent in calcifying aponeurotic fibroma
Authors: Puls Florian , Hofvander Jakob , Magnusson Linda , Nilsson Jenny , Haywood Elaine , Sumathi Vaiyapuri P , Mangham D Chas , Kindblom Lars‐Gunnar , Mertens Fredrik
Published: December 2015

Calcifying aponeurotic fibroma (CAF) is a soft tissue neoplasm with a predilection for the hands and feet in children and adolescents. Its molecular basis is unknown. We used chromosome banding analysis, fluorescence in situ hybridization (FISH), mRNA sequencing (RNA‐seq), RT‐PCR, and immunohistochemistry to characterize a series of CAFs. An insertion ins(2;4)(q35;q25q?) was identified in the index case. Fusion of the FN1 and EGF genes, mapping to the breakpoint regions on chromosomes 2 and 4, respectively, was detected by RNA‐seq and confirmed by RT‐PCR in the index case and two additional cases. FISH on five additional tumours identified FN1–EGF fusions in all cases. CAFs analysed by RT‐PCR showed that FN1 exon 23, 27 or 42 was fused to EGF exon 17 or 19. High‐level expression of the entire FN1 gene in CAF suggests that strong FN1 promoter activity drives inappropriate expression of the biologically active portion of EGF, which was detected immunohistochemically in 8/9 cases. The FN1–EGF fusion, which has not been observed in any other neoplasm, appears to be the main driver mutation in CAF. Although further functional studies are required to understand the exact pathogenesis of CAF, the composition of the chimera suggests an autocrine/paracrine mechanism of transformation. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Project Stakeholder Management—Past and Present
Authors: Eskerod Pernille , Huemann Martina , Savage Grant
Published: December 2015

In this special issue on project stakeholder management, the aim is to advance the understanding of this topic by looking into theory outside the project management field and by presenting findings from case studies. In this overview article, we identify the theoretical roots of the stakeholder concept and the current state of the field. We point to early proponents of stakeholder thinking. In addition, we point to recent concepts and developments outside the project management field that are relevant in the project management context; then, we introduce the articles included in the special issue; and, finally, we identify other relevant publications.
Topochemical effect in thermalE–Zisomerization of azodioxides in solid state
Authors: Varga Katarina , Vančik Hrvoj
Published: December 2015

The thermally inducedE–Zisomerization of the benzeneazodioxide derivatives is studied in the solid polycrystalline state. The reactions are studied from the kinetic and mechanistic aspects. In contrast to the solution, where isomerizations of azodioxides occur through the formation of corresponding nitroso monomers, the topochemical effect in solid state lead to the mechanism that includes formation of the “torsional” transition state, as it is the case in other known cis–trans isomerizations. It is proposed that both the reactions in solid state, the nitroso monomer–dimer equilibrium, and isomerization about the azodioxide NN bond tentatively involve similar transition states. Copyright © 2015 John Wiley & Sons, Ltd.
Polymers for application in organic solar cells: Bithiophene can work better than thienothiophene when coupled to benzodithiophene
Authors: Parenti Francesca , Ricciardi Rosa , Diana Rosita , Morvillo Pasquale , Fontanesi Claudio , Tassinari Francesco , Schenetti Luisa , Minarini Carla , Mucci Adele
Published: December 2015

The synthesis and characterization of two low band gap copolymers (P1 and P2) incorporating benzo[1,2‐b:4,5‐b']dithiophene unit substituted with octylsulfanylthienyl groups (OSBT) are here reported. These materials, designed to be employed in polymer solar cells (PSCs), were obtained from alternating OSBT and bithiophene (P1) or thienothiophene (P2) units. Their structural electrochemical and photophysical properties were investigated. They are thermally stable and soluble in organic solvents from which they easily form films. They also form π‐stacks in solution, in film and display a moderate solvatochromism. These polymers were tested with [70]PCBM in bulk‐heterojunction (BHJ) PSCs where they act as donor materials and [70]PCBM is the electron acceptor. The best device, obtained using a 1:3 weight ratio for the P1:[70]PCBM blend, shows a PCE around 1.5%. A broad response from 350 to 700 nm is also observed in the external quantum efficiency (EQE) curves, wider for P1 with respect to P2. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 1603–1614
Fragment Velocity Distribution of Velocity Enhanced Warhead under Double Symmetric Initiations
Authors: Wang Li , Han Feng , Chen Fang
Published: December 2015

Cylindrical casing filled with charge under eccentric point initiation is a kind of velocity enhanced warhead (VEW). The initial velocity distribution of fragments from VEW is a key issue in the field of explosive technology. Most of the formulas existed can predict the fragment velocity distribution from VEW with a single eccentric initiation point, but the fragment velocity distribution of the VEWs with double symmetric eccentric initiation points is not studied well. In this paper, a new formula is established to predict the radial distribution of the fragment velocities from VEW under double symmetric initiation points. Not only the maximum velocity gains, but also the velocity gains with azimuth angle can be calculated using this formula. The formula applies a correctional function in consideration of both the angle 2ϕ between the two symmetric initiation points and the ratio of the mass charge to that of metal casing β. Finally, the X‐ray experiments were conducted to verify the formula established in this paper, and the predictions agree well with the experimental data. According to the comparisons between the calculated results from the formula and the published data, the formula also shows good agreement.
Prognostic factors for clinical outcomes in patients with metastatic castration resistant prostate cancer treated with sequential novel androgen receptor‐directed therapies
Authors: Nadal Rosa , Tsai Hua‐Ling , Sinibaldi Victoria J. , Paller Channing J. , Antonarakis Emmanuel S. , Denmeade Sammuel R. , Carducci Michael A. , Eisenberger Mario A.
Published: December 2015

BACKGROUND

Prognostic factors associated with clinical outcomes in patients with metastatic castration‐resistant prostate cancer (mCRPC) treated with a novel androgen receptor‐directed therapies (ARDT) in the second line setting has not been formally evaluated.

PATIENTS AND METHODS

We retrospectively reviewed and analyzed medical records of all patients with mCRPC who received sequential treatment with ARDT. We analyzed potential clinical factors associated with post treatment endpoints including 50% decline in prostatic‐specific antigen (PSA), PSA‐progression‐free survival (PFS), clinical or radiographic PFS and overall survival (OS). Prognostic univariate and multivariate Cox proportional hazard models were developed and assessed.

RESULTS

One hundred twenty‐six patients with mCRPC treated with a second‐line novel ARDT were included. Overall, 50% decline in PSA was observed in 22% of patients and a median PSA‐PFS of 2.9 months and a PFS of 3.6 months. After adjusting for potential confounders including prior exposure to docetaxel and number of prior antiandrogen agents, time to development of CRPC was an independent factor associated with PSA‐PFS (hazard ratio [HR]: 0.99; 95% confidence interval [CI]: 0.99–1; P = 0.02) and PFS (HR: 0.99; CI: 0.98–1; P= 0.01). PSA response (50% decline) to first‐line novel ARDT correlated negatively with PSA‐PFS with second‐line novel ARDT (HR: 1.7; 95% CI: 1.14–2.53; P = 0.009) and lower pre‐treatment levels of albumin were associated with shorter PFS (HR: 0.56; 95% CI: 0.32‐0.97; P = 0.03). Performance status, pre‐treatment levels of albumin, extent of disease and time to development CRPC were associated with OS.

CONCLUSIONS

Second‐line ARDT is associated with modest outcomes in patients with mCRPC. Time to development of CRPC is the strongest predictor of PSA response, PSA‐PFS and OS which suggest that intrinsic resistance to AR directed treatment is the major treatment outcome factor in these patients. Future studies in patients receiving long term ARTD should include the identification of predictive biomarkers to facilitate treatment selection. Prostate 76:512–520, 2016. © 2015 Wiley Periodicals, Inc.
Chronic P‐glycoprotein inhibition increases the brain concentration of escitalopram: potential implications for treating depression
Authors: O'Brien Fionn E. , Moloney Gerard M. , Scott Karen A. , O'Connor Richard M. , Clarke Gerard , Dinan Timothy G. , Griffin Brendan T. , Cryan John F.
Published: December 2015

Recent preclinical studies have revealed a functionally important role for the drug efflux pump P‐glycoprotein (P‐gp) at the blood–brain barrier in limiting brain levels and thus antidepressant‐like activity of certain antidepressant drugs. Specifically, acute administration of P‐gp inhibitors, such as verapamil and cyclosporin A (CsA), has been shown to augment brain concentrations and functional activity of the antidepressant escitalopram in rodents. However, depression is a chronic disorder and current treatments require prolonged administration to elicit their full therapeutic effect. Thus, it is important to investigate whether acute findings in relation to P‐gp inhibition translate to chronic paradigms. To this end, the present study investigates whether chronic treatment with the P‐gp inhibitor verapamil and the antidepressant escitalopram results in enhanced brain distribution and antidepressant‐like effects of escitalopram. Verapamil (10 mg·kg−1 i.p.) and escitalopram (0.1 mg·kg−1 i.p.) were administered once daily for 22 days. On the final day of treatment, brain regions and plasma were collected for analysis of cortical and plasma escitalopram concentrations, and to determine the hippocampal expression of genes previously reported to be altered by chronic antidepressant treatment. Verapamil treatment resulted in a greater than twofold increase in brain levels of escitalopram, without altering plasma levels. Neither gene expression analysis nor behavioral testing revealed an augmentation of responses to escitalopram treatment due to verapamil administration. Taken together, these data demonstrate for the first time that P‐gp inhibition can yield elevated brain concentrations of an antidepressant after chronic treatment. The functional relevance of these increased brain levels requires further elaboration.
Green laser diodes with low operation voltage obtained by suppressing carbon impurity in AlGaN: Mg cladding layer
Authors: Tian Aiqin , Liu Jianping , Zhang Liqun , Ikeda Masao , Zhang Shuming , Li Deyao , Fan Xiaowang , Zhou Kun , Wen Pengyan , Zhang Feng , Yang Hui
Published: December 2015

Electrical properties of Al0.07Ga0.93N: Mg samples with different carbon impurity concentrations were investigated by Hall measurements. By reducing carbon impurity concentration from 2×1018 cm‐3 to 5×1016 cm‐3, the resistivity of p‐Al0.07Ga0.93N decreases from 7.4 Ω·cm to 2.2 Ω·cm. By applying the growth conditions of low‐temperature AlGaN: Mg with low carbon incorporation to cladding layer of green LD structure, we have obtained green LDs with series resistance as low as 2.4 Ω and operation voltage of 4.9 V at 4 kA/cm2. The green LDs lased at 508 nm with a threshold current density of 8.5 kA/cm2and a slope efficiency of 0.22 W/A. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Design of GaN‐based surface plasmon LEDs to enhance the modulation bandwidth and light output
Authors: Liu Lei , Zhao Lixia , Zhu Shichao , Yu Zhiguo , An Pingbo , Yang Chao , Wu Chunhui , Li Jinmin
Published: December 2015

Gallium nitride based light emitting diodes have shown their advantages in the application of visible light communication (VLC) besides general illumination. However, the modulation bandwidth of current commercial GaN based LEDs still cannot meet daily application of VLC. It has been reported that the modulation bandwidth can be enhanced by the surface plasmon due to the coupling between the surface plasmon and the active region of LEDs. However, the light output may be decreased. In this study, we designed a GaN‐based surface plasmon LEDs using lateral coupling to both increase the light output and the modulation bandwidth. The finite difference time domain method was utilized to investigate the modulation bandwidth of the GaN‐based surface plasmon LEDs as well as the light output. Simulation results show that the modulation bandwidth was estimated to be ∼2.3 GHz with 2.5 times enhancement of the light output compared with conventional LED structure. This design of surface plasmon LEDs will be useful for applications in high frequency visible light communication. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
LTQ Orbitrap Velos in routine de novo sequencing of non‐tryptic skin peptides from the frog Rana latastei with traditional and reliable manual spectra interpretation
Authors: Samgina Tatiana Yu. , Tolpina Miriam D. , Trebse Polonca , Torkar Gregor , Artemenko Konstantin A. , Bergquist Jonas , Lebedev Albert T.
Published: December 2015

Rationale

Mass spectrometry has shown itself to be the most efficient tool for the sequencing of peptides. However, de novo sequencing of novel natural peptides is significantly more challenging in comparison with the same procedure applied for the tryptic peptides. To reach the goal in this case it is essential to select the most efficient methods of triggering fragmentation and combine all the possible complementary techniques.

Methods

Collision‐induced dissociation (CID), high‐energy collision dissociation (HCD), and electron‐transfer dissociation (ETD) tandem mass spectra recorded with a LTQ Orbitrap Velos instrument were used for the elucidation of the sequence of the natural non‐tryptic peptides from the skin secretion of Rana latastei. Manual interpretation of the spectra was applied.

Results

The combined approach using CID, HCD, and ETD tandem mass spectra of the multiprotonated peptides in various charge states, as well as of their proteolytic fragments, allowed the sequences of seven novel peptides from the skin secretion of Rana latastei to be established.

Conclusions

Manual mass spectrometry sequencing of natural non‐tryptic peptides from the skin secretion of Rana latastei provided the opportunity to work successfully with these species and demonstrated once again its advantage over automatic approaches. Copyright © 2015 John Wiley & Sons, Ltd.
Ontogenic growth as the root of fundamental differences between childhood and adult cancer
Authors: Werner Benjamin , Traulsen Arne , Dingli David
Published: December 2015

Cancer, the unregulated proliferation of cells, can occur at any age and may arise from almost all cell types. However, the incidence and types of cancer differ with age. Some cancers are predominantly observed in children, others are mostly restricted to older ages. Treatment strategies of some cancers are very successful and cure is common in childhood, while treatment of the same cancer type is much more challenging in adults. Here, we develop a stochastic model of stem cell proliferation that considers both tissue development and homeostasis and discuss the disturbance of such a system by mutations. Due to changes in population size, mutant fitness becomes context dependent and consequently the effects of mutations on the stem cell population can vary with age. We discuss different mutant phenotypes and show the age dependency of their expected abundances. Most importantly, fitness of particular mutations can change with age and advantageous mutations can become deleterious or vice versa. This perspective can explain unique properties of childhood disorders, for example, the frequently observed phenomenon of a self-limiting leukemia in newborns with trisomy 21, but also explains other puzzling observations such as the increased risk of leukemia in patients with bone marrow failure or chemotherapy induced myelodysplasia.
Early experiences and integration in the persistence of first‐generation college students in STEM and non‐STEM majors
Authors: Dika Sandra L. , D'Amico Mark M.
Published: December 2015

Representation of diverse groups in science, technology, engineering, and mathematics (STEM) fields is a persistent concern in the United States. Although there have been some strides toward more diverse representation, significant problems of underrepresentation remain in particular STEM fields: physical sciences, engineering, math, and computer sciences (PEMC). The purpose of this study is to understand the significance of pre‐college personal and academic factors along with early college experiences to explain persistence among first‐generation college students (FGCS) considering possible differences among PEMC‐STEM majors, other‐STEM majors, and non‐STEM majors. Using institutional and survey data from one 4‐year urban research institution in the Southeast, logistic regression models demonstrate the importance of early academic performance (first‐semester GPA) to increase odds of FGCS persistence across majors; and also reveal important differences. Besides early academic performance, the only other significant factor for persistence of PEMC‐STEM majors was perceived preparation in math. Perceived social fit was significant for persistence for the other‐STEM and non‐STEM majors, whereas perceived academic fit was only significant for non‐STEM majors. These results align generally with previous research, and also suggest that examining differences among STEM subgroups may help develop more nuanced understandings of the needs of different groups. © 2015 Wiley Periodicals, Inc. J Res Sci Teach 53: 368–383, 2016
What do we mean by science education for civic engagement?
Authors: Rudolph John L. , Horibe Shusaku
Published: December 2015

One of the most frequently cited goals for science education over the years has been to provide students with the understanding and skills necessary to engage in science‐related civic issues. Despite the repeated insistence on the importance of this kind of democratic participation, there has been little effort in the research community either to define just what science‐related civic engagement entails or to ask whether the research or practices in the field are suited to accomplishing this goal. In this paper we take a step toward this end by offering a precise definition of science‐related civic engagement drawing on work from the fields of philosophy and political theory. We argue that such engagement can be found in instances requiring both the use and production of scientific knowledge and examine the various avenues of that engagement. We then explore some implications such a definition might have for thinking about science education research and practice. © 2015 Wiley Periodicals, Inc. J Res Sci Teach 53: 805–820, 2016