bluuebunny/crossref_metadata_2025 huggingface dataset:
Steps Toward Harmonization for Clinical Development of Medicines in Pediatric Ulcerative Colitis—A Global Scientific Discussion, Part 1
Authors: Sun Haihao , Vesely Richard , Taminiau Jan , Szitanyi Peter , Papadopoulos Elektra J. , Isaac Maria , Klein Agnes , Uzu Shinobu , Griebel Donna , Mulberg Andrew E.
Published: January 2014

Objectives:

There is a pressing need for drug development in pediatric ulcerative colitis (UC). Lack of scientific consensus on efficacy endpoints and disease outcome assessments presents a hurdle for global drug development in pediatric UC. Scientists from 4 regulatory agencies convened an International Inflammatory Bowel Disease Working Group (i‐IBD Working Group) to harmonize present thinking about various aspects of drug development in pediatric UC globally.

Methods:

The i‐IBD Working Group was convened in 2012 by scientists from the US Food and Drug Administration, European Medicines Agency, Health Canada, and the Pharmaceuticals and Medical Devices Agency of Japan. The members of this group considered reasons for differences in their acceptance of efficacy endpoints and disease activity indices used in pediatric UC, reviewed the available literature, and developed consensus opinions regarding approaches for evaluating outcomes in pediatric UC trials.

Results:

There is lack of harmonization in using efficacy endpoint and outcome assessments including disease activity indices to assess clinical benefit in pediatric UC trials. Many disease activity indices have been developed, but their biometric properties, such as responsiveness, reliability, and validity, have not been properly validated. Biomarkers, such as fecal calprotectin and lactoferrin, are being investigated for their potential as noninvasive surrogate endpoints in UC.

Conclusions:

Consensus on the efficacy endpoints, disease activity indices, and outcome assessments is needed for globalization of pediatric UC trials. The i‐IBD Working Group offers several perspectives to facilitate harmonization across regions. The development of noninvasive biomarkers as reliable surrogate endpoints needs to be explored further.
Switching ferroelectric domain configurations using both electric and magnetic fields in Pb(Zr,Ti)O
3
–Pb(Fe,Ta)O
3
single-crystal lamellae
Authors: Evans D. M. , Schilling A. , Kumar Ashok , Sanchez D. , Ortega N. , Katiyar R. S. , Scott J. F. , Gregg J. M.
Published: January 2014

Thin single-crystal lamellae cut from Pb(Zr,Ti)O
3
–Pb(Fe,Ta)O
3
ceramic samples have been integrated into simple coplanar capacitor devices. The influence of applied electric and magnetic fields on ferroelectric domain configurations has been mapped, using piezoresponse force microscopy. The extent to which magnetic fields alter the ferroelectric domains was found to be strongly history dependent: after switching had been induced by applying electric fields, the susceptibility of the domains to change under a magnetic field (the effective magnetoelectric coupling parameter) was large. Such large, magnetic field-induced changes resulted in a remanent domain state very similar to the remanent state induced by an electric field. Subsequent magnetic field reversal induced more modest ferroelectric switching.
Magnetocapacitance without magnetism
Authors: Parish Meera M.
Published: January 2014

A substantial magnetodielectric effect is often an indication of coupled magnetic and elastic order, such as is found in the multi-ferroics. However, it has recently been shown that magnetism is not necessary to produce either a magnetoresistance or a magnetocapacitance when the material is inhomogeneous. Here, we will investigate the characteristic magnetic-field-dependent dielectric response of such an inhomogeneous system using exact calculations and numerical simulations of conductor–dielectric composites. In particular, we will show that even simple conductor–dielectric layers exhibit a magneto-capacitance, and thus random bulk inhomogeneities are not a requirement for this effect. Indeed, this work essentially provides a natural generalization of the Maxwell–Wagner effect to finite magnetic field. We will also discuss how this phenomenon has already been observed experimentally in some materials.
Evaluation of heterosubtypic cross-protection against highly pathogenic H5N1 by active infection with human seasonal influenza A virus or trivalent inactivated vaccine immunization in ferret models
Authors: Park Su-Jin , Kim Eun-Ha , Pascua Philippe Noriel Q. , Kwon Hyeok-Il , Lim Gyo-Jin , Decano Arun , Kim Se Mi , Song Man Ki , Shin Eui-Cheol , Choi Young-Ki
Published: January 2014

The threat of highly pathogenic avian influenza (HPAI) H5N1 viruses to cause the next pandemic remains a major concern. Here, we evaluated the cross-protection induced by natural infection of human seasonal influenza strains or immunization with trivalent inactivated influenza vaccine (TIV) against HPAI H5N1 (A/Vietnam/1203/2004) virus in ferrets. Groups were treated with PBS (group A), infected with H1N1 (group B) or H3N2 (group C) virus, or immunized with TIV (group D). Twelve weeks after the last treatment, serological assays revealed that groups B and C, but not group D, sustained moderate immunogenicity against homologous viruses; cross-reactivity against the H5N1 virus was not detected in any group. Following challenge with A/Vietnam/1203/2004 (H5N1) virus, only groups B and C exhibited attenuated viral loads leading to 100 % survival. Our data suggest that natural infection with human seasonal strains could potentially provide better heterosubtypic protection against HPAI H5N1 virus infection compared to TIV immunization.
Characterization of cell-to-cell variation in nuclear transport rates and identification of its sources
Authors: Durrieu Lucía , Bush Alan , Grande Alicia , Johansson Rikard , Janzén David , Katz Andrea , Cedersund Gunnar , Colman-Lerner Alejandro
Published: January 2014

Nuclear transport is an essential part of eukaryotic cell function. Several assays exist to measure the rate of this process, but not at the single-cell level. Here, we developed a fluorescent recovery after photobleaching (FRAP)- based method to determine nuclear import and export rates independently in individual live cells. To overcome the inherent noise of single-cell measurements, we performed sequential FRAPs on the same cell. We found large cell-to-cell variation in transport rates within isogenic yeast populations. Our data suggest that a main determinant of this heterogeneity may be variability in the number of nuclear pore complexes (NPCs). For passive transport, this component explained most of the variability. Actively transported proteins were influenced by variability in additional components, including general factors such as the Ran-GTP gradient as well as specific regulators of the export rate. By considering mother-daughter pairs, we showed that mitotic segregation of the transport machinery is too noisy to control cellular inheritance. Finally, we studied mother-daughter cell asymmetry in the localization of the transcription factor Ace2, which is specifically concentrated in daughter cell nuclei. We found that this asymmetry is the outcome of a higher ratio of import rate to export rate in daughters. Interestingly, rather than reduced export in the daughter cell, as previously hypothesized, rates of both import and export are faster in daughter cells than in mother cells, but the magnitude of increase is greater for import. These results shed light into cell-to-cell variation in cellular dynamics and its sources.
Chromothripsis-like patterns are recurring but heterogeneously distributed features in a survey of 22,347 cancer genome screens
Authors: Cai Haoyang , Kumar Nitin , Bagheri Homayoun C. , von Mering Christian , Robinson Mark D. , Baudis Michael
Published: January 2014

Background

Chromothripsis is a recently discovered phenomenon of genomic rearrangement, possibly arising during a single genome-shattering event. This could provide an alternative paradigm in cancer development, replacing the gradual accumulation of genomic changes with a “one-off” catastrophic event. However, the term has been used with varying operational definitions, with the minimal consensus being a large number of locally clustered copy number aberrations. The mechanisms underlying these chromothripsis-like patterns (CTLP) and their specific impact on tumorigenesis are still poorly understood.

Results

Here, we identified CTLP in 918 cancer samples, from a dataset of more than 22,000 oncogenomic arrays covering 132 cancer types. Fragmentation hotspots were found to be located on chromosome 8, 11, 12 and 17. Among the various cancer types, soft-tissue tumors exhibited particularly high CTLP frequencies. Genomic context analysis revealed that CTLP rearrangements frequently occurred in genomes that additionally harbored multiple copy number aberrations (CNAs). An investigation into the affected chromosomal regions showed a large proportion of arm-level pulverization and telomere related events, which would be compatible to a number of underlying mechanisms. We also report evidence that these genomic events may be correlated with patient age, stage and survival rate.

Conclusions

Through a large-scale analysis of oncogenomic array data sets, this study characterized features associated with genomic aberrations patterns, compatible to the spectrum of “chromothripsis”-definitions as previously used. While quantifying clustered genomic copy number aberrations in cancer samples, our data indicates an underlying biological heterogeneity behind these chromothripsis-like patterns, beyond a well defined “chromthripsis” phenomenon.
Reconstructing complex regions of genomes using long-read sequencing technology
Authors: Huddleston John , Ranade Swati , Malig Maika , Antonacci Francesca , Chaisson Mark , Hon Lawrence , Sudmant Peter H. , Graves Tina A. , Alkan Can , Dennis Megan Y. , Wilson Richard K. , Turner Stephen W. , Korlach Jonas , Eichler Evan E.
Published: January 2014

Obtaining high-quality sequence continuity of complex regions of recent segmental duplication remains one of the major challenges of finishing genome assemblies. In the human and mouse genomes, this was achieved by targeting large-insert clones using costly and laborious capillary-based sequencing approaches. Sanger shotgun sequencing of clone inserts, however, has now been largely abandoned, leaving most of these regions unresolved in newer genome assemblies generated primarily by next-generation sequencing hybrid approaches. Here we show that it is possible to resolve regions that are complex in a genome-wide context but simple in isolation for a fraction of the time and cost of traditional methods using long-read single molecule, real-time (SMRT) sequencing and assembly technology from Pacific Biosciences (PacBio). We sequenced and assembled BAC clones corresponding to a 1.3-Mbp complex region of chromosome 17q21.31, demonstrating 99.994% identity to Sanger assemblies of the same clones. We targeted 44 differences using Illumina sequencing and find that PacBio and Sanger assemblies share a comparable number of validated variants, albeit with different sequence context biases. Finally, we targeted a poorly assembled 766-kbp duplicated region of the chimpanzee genome and resolved the structure and organization for a fraction of the cost and time of traditional finishing approaches. Our data suggest a straightforward path for upgrading genomes to a higher quality finished state.
(E)-N′-[4-(Dimethylamino)benzylidene]-2-(4-methylphenoxy)acetohydrazide
Authors: Usha M. K. , Madan Kumar S. , Nitinchandra  , Kalluraya B. , Lokanath N. K. , Revannasiddaiah D.
Published: January 2014

In the title compound, C18H21N3O2, the dihedral angle between the benzene rings is 68.85 (11)°. In the crystal, the molecules are linked by C—H...O and N—H...O hydrogen bonds, as well as weak C—H...π contacts, forming a three-dimensional supramolecular architecture.
μ-1,6,7,12-Tetraazaperylene-κ4N1,N12:N6,N7-bis[chlorido(η6-p-cymene)ruthenium(II)] bis(hexafluoridophosphate) acetone disolvate
Authors: Brietzke Thomas , Kässler Daniel , Kelling Alexandra , Schilde Uwe , Holdt Hans-Jürgen
Published: January 2014

In the title compound, [Ru2(C10H14)2Cl2(C16H8N4)](PF6)2·2C3H6O, the binuclear RuIIcomplex dication, [{RuCl(η6-cym)}2(μ-tape)]2+, built up by a planar 1,6,7,12-tetraazaperylene (tape) bridge, two η6-bound cymene (cym) ligands and two chloride ligands, includes an inversion center. The RuIIatom shows the typical piano-stool motif for arene coordination. The counter-charge is provided by a hexafluoridophosphate anion and the asymmetric unit is completed by an acetone molecule of crystallization. The components of the structure are connected into a three-dimensional architecture by C—H...O/F/Cl interactions.
A second polymorph of (Z)-3-amino-4-(2-phenylhydrazinylidene)-1H-pyrazol-5(4H)-one
Authors: Elgazwy Abdel-Sattar S. Hamad , Jones Peter G.
Published: January 2014

The molecule of the title compound, C9H9N5O, is approximately planar (the r.m.s. deviation of all non-H atoms is 0.08 Å). The amine substituent is pyramidal at the N atom. An intramolecular N—Hhydrazine...O=C hydrogen bond is present. In the crystal, molecules are connectedviaN—H...N and N—H...O hydrogen bonds, forming infinite layers parallel to (010). This polymorph is triclinic, space groupP-1, whereas the previously reported form was monoclinic, space groupP21/c[Elgemeieet al.(2013).Acta Cryst. E69, o187], with stepped layers and a significantly lower density.
The mixed-metal tris(disulfide) thiophosphate, KNb1.77Ta0.23PS10
Authors: Lee Yoonjeong , Yoon Woojin , Yun Hoseop
Published: January 2014

The title compoundcatena-poly[potassium [tri-μ-disulfido-μ-tetrathiophosphato-di[niobate(IV)/tantalate(IV)(0.885/0.115)]]], has been obtained through the reaction of the elements with KCl. The title compound is isostructural with KNb2PS10, with the Nb sites occupied by statistically disordered Nb (88.5%) and Ta (11.5%) atoms. The structure is composed of anionic∞1[M2PS10]−chains along [100] (M= Nb/Ta) and K+ions. This chain is built up from distorted bicapped trigonal prisms [MS8] and [PS4] tetrahedra. There are no interchain bonding interactions, except for electrostatic and van der Waals forces. The S22−and S2−anionic species and theM4+–M4+pair [M—M= 2.8939 (3) Å] are observed. The classical charge balance is represented by [K+][M4+]2[PS43−][S22−]3.
PNPLA3 gene polymorphism accounts for fatty liver in community subjects without metabolic syndrome
Authors: Shen J. , Wong G. L.‐H. , Chan H. L.‐Y. , Chan H.‐Y. , Yeung D. K.‐W. , Chan R. S.‐M. , Chim A. M.‐L. , Chan A. W.‐H. , Choi P. C.‐L. , Woo J. , Chu W. C.‐W. , Wong V. W.‐S.
Published: January 2014

Background

The rs738409 GG variant in patatin‐like phospholipase 3 (PNPLA3) is associated with non‐alcoholic fatty liver disease (NAFLD) and disease severity. However, it remains unclear if it contributes to the development of NAFLD through affecting dietary pattern.

Aim

To examine the association among PNPLA3 gene polymorphism, dietary pattern, metabolic factors and NAFLD.

Methods

Liver fat and fibrosis were assessed by proton‐magnetic resonance spectroscopy and transient elastography in 920 subjects from a population screening project (251 had NAFLD). Dietary nutrient intake was recorded using a locally validated food‐frequency questionnaire.

Results

The prevalence of GG genotype in NAFLD subjects was 20.7%, compared to 10.6% in controls (P < 0.001). Macronutrient intake was similar among subjects with different PNPLA3 genotypes. The presence of G allele was a predictor of NAFLD independent of nutrient intake and other metabolic factors (adjusted odds ratio to CC: CG, 2.00; GG, 2.68). In subjects without metabolic syndrome, G allele was even more closely correlated with NAFLD diagnosis (adjusted odds ratio to CC: CG, 2.22; GG, 3.39). The prevalence of NAFLD was only 12% in subjects with CC genotype and no metabolic syndrome, and increased to 34% in those with GG genotype and no metabolic syndrome. While NAFLD subjects had significantly lower fibre intake, there was no significant interaction between PNPLA3 and dietary pattern.

Conclusions

The G allele in PNPLA3 rs738409 increases the risk of NAFLD in the general population, especially in subjects without metabolic syndrome, independent of dietary pattern and metabolic factors.
Absolute beat‐to‐beat variability and instability parameters of ECG intervals: biomarkers for predicting ischaemia‐induced ventricular fibrillation
Authors: Sarusi Annamária , Rárosi Ferenc , Szűcs Mónika , Csík Norbert , Farkas Attila S , Papp Julius Gy , Varró András , Forster Tamás , Curtis Michael J , Farkas András
Published: January 2014

Background and Purpose

Predicting lethal arrhythmia liability from beat‐to‐beat variability and instability (BVI) of the ECG intervals is a useful technique in drug assessment. Most investigators use only arrhythmia‐free ECGs for this. Recently, it was shown that drug‐induced torsades de pointes (TdP) liability can be predicted more accurately from BVI measured irrespective of rhythm, even during arrhythmias (absolute BVI). The present study tested the broader applicability of this assessment by examining whether absolute BVI parameters predict another potential lethal arrhythmia, ischaemia‐induced ventricular fibrillation (VF).

Experimental Approach

Langendorff‐perfused rat hearts were subjected to regional ischaemia for 15 min. Absolute BVI parameters were derived from ECG intervals measured in 40 consecutive ventricular complexes (irrespective of rhythm) immediately preceding VF onset and compared with time‐matched values in hearts not expressing VF.

Key Results

Increased frequency of non‐sinus beats and ‘R on T’ arrhythmic beats, shortened mean RR and electrical diastolic intervals, and increased BVI of cycle length and repolarization predicted VF occurrence. Absolute BVI parameters that quantify variability of repolarization (e.g. ‘short‐term variability’ of QT interval) had the best predictive power with high sensitivity and specificity. In contrast, VF was not predicted by any BVI parameter derived from the last arrhythmia‐free interlude before VF.

Conclusions and Implications

The novel absolute BVI parameters that predicted TdP in rabbit also predict ischaemia‐induced VF in rat, indicating a diagnostic and mechanistic congruence. Repolarization inhomogeneity represents a pivotal biomarker of ischaemia‐induced VF. The newly validated biomarkers could serve as surrogates for VF in pre‐clinical drug investigations.
Assessing the Distribution and Protection Status of two Types of Cool Environment to Facilitate Their Conservation under Climate Change
Authors: GOLLAN JOHN R. , RAMP DANIEL , ASHCROFT MICHAEL B.
Published: January 2014

Strategies to mitigate climate change can protect different types of cool environments. Two are receiving much attention: protection of ephemeral refuges (i.e., places with low maximum temperatures) and of stable refugia (i.e., places that are cool, have a stable environment, and are isolated). Problematically, they are often treated as equivalents. Careful delineation of their qualities is needed to prevent misdirected conservation initiatives; yet, no one has determined whether protecting one protects the other. We mapped both types of cool environments across a large (∼3.4M ha) mixed‐use landscape with a geographic information system and conducted a patch analysis to compare their spatial distributions; examine relations between land use and their size and shape; and assess their current protection status. With a modest, but arbitrary, threshold for demarcating both types of cool environments (i.e., values below the 0.025 quantile) there were 146,523 ha of ephemeral refuge (62,208 ha) and stable refugia (62,319 ha). Ephemeral refuges were generally aggregated at high elevation, and more refuge area occurred in protected areas (55,184 ha) than in unprotected areas (7,024 ha). In contrast, stable refugia were scattered across the landscape, and more stable‐refugium area occurred on unprotected (40,135 ha) than on protected land (22,184 ha). Although sensitivity analysis showed that varying the thresholds that define cool environments affected outcomes, it also exposed the challenge of choosing a threshold for strategies to address climate change; there is no single value that is appropriate for all of biodiversity. The degree of overlap between ephemeral refuges and stable refugia revealed that targeting only the former for protection on currently unprotected land would capture ∼17% of stable refugia. Targeting only stable refugia would capture ∼54% of ephemeral refuges. Thus, targeting one type of cool environment did not fully protect the other.

Evaluación de la Distribución y Estado de Protección de Dos Tipos de Ambientes Fríos para Facilitar su Conservación bajo el Cambio Climático
Assessment of Association between Common Variants at 17q12 and Prostate Cancer Risk—Evidence from Serbian Population and Meta‐Analysis
Authors: Nikolić Zorana Z. , Branković Ana S. , Savić‐Pavićević Dušanka L.J. , Preković Stefan M. , Vukotić Vinka D. , Cerović Snežana J. , Filipović Nataša N. , Tomović Saša M. , Romac Stanka P. , Brajušković Goran N.
Published: January 2014

This study aimed to evaluate possible association between genotypes and alleles of two 17q12 polymorphisms (rs3760511 and rs7501939) and prostate cancer (PCa) risk and progression. Two hundred seventy‐one patients with PCa, 261 patients with benign prostatic hyperplasia (BPH), and 171 controls were included in the study. Single nucleotide polymorphisms (SNPs) were genotyped by using PCR followed by restriction fragment length (PCR‐RFLP) analysis. We conducted meta‐analysis of published studies regarding association of these SNPs with PCa risk. Evidence of positive association between the AC genotype of the SNP rs3760511 and BPH risk for the best‐fitting overdominant model of association (BPH vs. controls comparison, p = 0.026; odds ratio [OR] = 1.58; 95% confidence interval [95%CI] 1.05–2.36) were obtained. The association between T allele of rs7501939 and PCa risk was determined in PCa versus controls comparison (p = 0.0032; OR = 0.66, 95%CI 0.50–0.87) with the best‐fitting model of inheritance being log‐additive. This variant was also found to be associated with the risk of BPH (p = 0.0023; OR = 0.65, 95%CI 0.49–0.86). We found no association between parameters of PCa progression and the analyzed SNPs. Meta‐analysis showed strong association between these variants and PCa risk. Our study shows association between SNPs at locus 17q12 and the risk of prostatic diseases in Serbian population. At the same time, results of meta‐analysis suggest the association of these SNPs with PCa risk.
Serum 25‐hydroxyvitamin D3 levels affect treatment outcome in pegylated interferon/ribavirin combination therapy for compensated cirrhotic patients with hepatitis C virus genotype 1b and high viral load
Authors: Atsukawa Masanori , Tsubota Akihito , Shimada Noritomo , Kondo Chisa , Itokawa Norio , Nakagawa Ai , Hashimoto Satomi , Fukuda Takeshi , Matsushita Yoko , Narahara Yoshiyuki , Iwakiri Katsuhiko , Nakatsuka Katsuhisa , Kawamoto Chiaki , Sakamoto Choitsu
Published: January 2014

Aim

Much is unknown about the effect of 25‐hydroxyvitamin D3 levels on the outcome of pegylated interferon/ribavirin (PEG IFN/RBV) therapy for hepatitis C virus‐related cirrhosis. The purpose of the present study was to analyze and elucidate factors, including 25‐hydroxyvitamin D3, that contribute to a sustained virological response (SVR) in patients with cirrhosis.

Methods

We analyzed whether 25‐hydroxyvitamin D3 contributes to the response to PEG IFN/RBV therapy among 134 cirrhotic patients.

Results

SVR was achieved in 43 patients. The median 25‐hydroxyvitamin D3 level was 20 ng/mL. Univariate analysis showed that the following factors contributed to SVR: low‐density lipoprotein cholesterol, albumin, 25‐hydroxyvitamin D3, core a.a.70 (a.a.70) substitutions, the number of mutations at the interferon sensitivity‐determining region and IL28B genotype. Multivariate analysis identified IL28B genotype and 25‐hydroxyvitamin D3 as independent factors contributing to SVR. Subsequently, SVR rate was examined by using 25‐hydroxyvitamin D3 and other important factors. The SVR rate was 51.8% in patients with core a.a.70 wild and ≥15 ng/mL of 25‐hydroxyvitamin D3, whereas the SVR rate was 7.1% in patients with core a.a.70 wild and <15 ng/mL of 25‐hydroxyvitamin D3. The SVR rate was 56.9% in patients with IL28B major genotype and ≥15 ng/mL of 25‐hydroxyvitamin D3. Surprisingly, the SVR rate was 0% in patients with IL28B minor genotype and <15 ng/mL of 25‐hydroxyvitamin D3.

Conclusion

IL28B genotype and 25‐hydroxyvitamin D3 were identified as independent factors contributing to SVR. Stratified analyses according to core a.a.70 substitution and IL28B genotype suggested that 25‐hydroxyvitamin D3 influences the outcome of PEG IFN/RBV therapy for cirrhosis.
Living and dying in a multi‐predator landscape of fear: roe deer are squeezed by contrasting pattern of predation risk imposed by lynx and humans
Authors: Lone Karen , Loe Leif Egil , Gobakken Terje , Linnell John D. C. , Odden John , Remmen Jørgen , Mysterud Atle
Published: January 2014

The theory of predation risk effects predicts behavioral responses in prey when risk of predation is not homogenous in space and time. Prey species are often faced with a tradeoff between food and safety in situations where food availability and predation risk peak in the same habitat type. Determining the optimal strategy becomes more complex if predators with different hunting mode create contrasting landscapes of risk, but this has rarely been documented in vertebrates. Roe deer in southeastern Norway face predation risk from lynx, as well as hunting by humans. These two predators differ greatly in their hunting methods. The predation risk from lynx, an efficient stalk‐and‐ambush predator is expected to be higher in areas with dense understory vegetation, while predation risk from human hunters is expected to be higher where visual sight lines are longer. Based on field observations and airborne LiDAR data from 71 lynx predation sites, 53 human hunting sites, 132 locations from 15 GPS‐marked roe deer, and 36 roe deer pellet locations from a regional survey, we investigated how predation risk was related to terrain attributes and vegetation classes/structure. As predicted, we found that increasing cover resulted in a contrasting lower predation risk from humans and higher predation risk from lynx. Greater terrain ruggedness increased the predation risk from both predators. Hence, multiple predators may create areas of contrasting risk as well as double risk in the same landscape. Our study highlights the complexity of predator–prey relationship in a multiple predator setting.

Synthesis

In this study of risk effects in a multi‐predator context, LiDAR data were used to quantify cover in the habitat and relate it to vulnerability to predation in a boreal forest. We found that lynx and human hunters superimpose generally contrasting landscapes of fear on a common prey species, but also identified double‐risk zones. Since the benefit of anti‐predator responses depends on the combined risk from all predators, it is necessary to consider complete predator assemblages to understand the potential for and occurrence of risk effects across study systems.
Inflammatory cytokines promote growth of intestinal smooth muscle cells by induced expression of PDGF‐Rβ
Authors: Nair Dileep G. , Miller Kurtis G. , Lourenssen Sandra R. , Blennerhassett Michael G.
Published: January 2014

Thickening of the inflamed intestinal wall involves growth of smooth muscle cells (SMC), which contributes to stricture formation. Earlier, the growth factor platelet‐derived growth factor (PDGF)‐BB was identified as a key mitogen for SMC from the rat colon (CSMC), and CSMC growth in colitis was associated with both appearance of its receptor, PDGF‐Rβ and modulation of phenotype. Here, we examined the role of inflammatory cytokines in inducing and modulating the growth response to PDGF‐BB. CSMC were enzymatically isolated from Sprague–Dawley rats, and the effect of tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β, transforming growth factor (TGF), IL‐17A and IL‐2 on CSMC growth and responsiveness to PDGF‐BB were assessed using proliferation assays, PCR and western blotting. Conditioned medium (CM) was obtained at 48 hrs of trinitrobenzene sulphonic acid‐induced colitis. Neither CM alone nor cytokines caused proliferation of early‐passage CSMC. However, CM from inflamed, but not control colon significantly promoted the effect of PDGF‐BB. IL‐1β, TNF‐α and IL‐17A, but not other cytokines, increased the effect of PDGF‐BB because of up‐regulation of mRNA and protein for PDGF‐Rβ without change in receptor phosphorylation. PDGF‐BB was identified in adult rat serum (RS) and RS‐induced CSMC proliferation was inhibited by imatinib, suggesting that blood‐derived PDGF‐BB is a local mitogen in vivo. In freshly isolated CSMC, CM from the inflamed colon as well as IL‐1β and TNF‐α induced the early expression of PDGF‐Rβ, while imatinib blocked subsequent RS‐induced cell proliferation. Thus, pro‐inflammatory cytokines both initiate and maintain a growth response in CSMC via PDGF‐Rβ and serum‐derived PDGF‐BB, and control of PDGF‐Rβ expression may be beneficial in chronic intestinal inflammation.
The Self‐Efficacy Scale for Preschool Teachers Regarding Asthma Care: Instrument Development and Validation
Authors: Gau Bih‐Shya , Hung Chao‐Chia
Published: January 2014

BACKGROUND

The purpose of this study was to develop and test the psychometric properties of a questionnaire that assesses preschool teachers' self‐efficacy in providing asthma care.

METHODS

A total of 407 teachers from 54 preschools in Taiwan participated in the study by completing the asthma management self‐efficacy scale. We assessed validity of the scale through expert opinion, exploratory factor analysis, and confirmatory factor analysis. The reliability of the scale was assessed using Cronbach's alpha.

RESULTS

A 10‐items questionnaire was developed to assess self‐efficacy concerning asthma treatment. On the basis of explorative factor analysis, 2 major factors emerged from the 10 self‐efficacy items that together explained 61.68% of the total variance in teachers' self‐efficacy with regard to asthma care. We named these factors “prevention of an asthma episode” and “the treatment of an asthma exacerbation.” Confirmatory factor analysis revealed that the 2‐factor model provided the best goodness‐of‐fit.

CONCLUSIONS

This scale could provide health professionals with useful information concerning preschool teachers' self‐efficacy with respect to the management of asthma in the preschool setting.
A phytochemical comparison of saw palmetto products using gas chromatography and 1H nuclear magnetic resonance spectroscopy metabolomic profiling
Authors: Booker Anthony , Suter Andy , Krnjic Ana , Strassel Brigitte , Zloh Mire , Said Mazlina , Heinrich Michael
Published: January 2014

Objectives

Preparations containing saw palmetto berries are used in the treatment of benign prostatic hyperplasia (BPH). There are many products on the market, and relatively little is known about their chemical variability and specifically the composition and quality of different saw palmetto products notwithstanding that in 2000, an international consultation paper from the major urological associations from the five continents on treatments for BPH demanded further research on this topic. Here, we compare two analytical approaches and characterise 57 different saw palmetto products.

Methods

An established method – gas chromatography – was used for the quantification of nine fatty acids, while a novel approach of metabolomic profiling using 1H nuclear magnetic resonance (NMR) spectroscopy was used as a fingerprinting tool to assess the overall composition of the extracts.

Key findings

The phytochemical analysis determining the fatty acids showed a high level of heterogeneity of the different products in the total amount and of nine single fatty acids. A robust and reproducible 1H NMR spectroscopy method was established, and the results showed that it was possible to statistically differentiate between saw palmetto products that had been extracted under different conditions but not between products that used a similar extraction method. Principal component analysis was able to determine those products that had significantly different metabolites.

Conclusions

The metabolomic approach developed offers novel opportunities for quality control along the value chain of saw palmetto and needs to be followed further, as with this method, the complexity of a herbal extract can be better assessed than with the analysis of a single group of constituents.
Fitness costs of rifampicin resistance in Mycobacterium tuberculosis are amplified under conditions of nutrient starvation and compensated by mutation in the β′ subunit of RNA polymerase
Authors: Song Taeksun , Park Yumi , Shamputa Isdore Chola , Seo Sunghwa , Lee Sun Young , Jeon Han‐Seung , Choi Hongjo , Lee Myungsun , Glynne Richard J. , Barnes S. Whitney , Walker John R. , Batalov Serge , Yusim Karina , Feng Shihai , Tung Chang‐Shung , Theiler James , Via Laura E. , Boshoff Helena I. M. , Murakami Katsuhiko S. , Korber Bette , Barry Clifton E. , Cho Sang‐Nae
Published: January 2014

Rifampicin resistance, a defining attribute of multidrug‐resistant tuberculosis, is conferred by mutations in the β subunit of RNA polymerase. Sequencing of rifampicin‐resistant (RIF‐R) clinical isolates of Mycobacterium tuberculosis revealed, in addition to RIF‐R mutations, enrichment of potential compensatory mutations around the double‐psi β‐barrel domain of the β′ subunit comprising the catalytic site and the exit tunnel for newly synthesized RNA. Sequential introduction of the resistance allele followed by the compensatory allele in isogenic Mycobacterium smegmatis showed that these mutations respectively caused and compensated a starvation enhanced growth defect by altering RNA polymerase activity. While specific combinations of resistance and compensatory alleles converged in divergent lineages, other combinations recurred among related isolates suggesting transmission of compensated RIF‐R strains. These findings suggest nutrient poor growth conditions impose larger selective pressure on RIF‐R organisms that results in the selection of compensatory mutations in a domain involved in catalysis and starvation control of RNA polymerase transcription.
Biological and clinical significance of the intratumour heterogeneity of PTEN protein expression and the corresponding molecular abnormalities of the PTEN gene in glioblastomas
Authors: Idoate Miguel A. , Echeveste Jose , Diez‐Valle Ricardo , Lozano Maria Dolores , Aristu José
Published: January 2014

Aims

Glioblastomas display marked phenotypic and molecular heterogeneity. The expression of the PTEN protein in glioblastomas also shows great intratumour heterogeneity, but the significance of this heterogeneity has so far received little attention.

Methods

We conducted a comparative study on paraffin and frozen samples from 60 glioblastomas. Based on PTEN immunostaining, paraffin glioblastomas were divided into positive (homogeneous staining) and both positive and negative (heterogeneous staining) tumours. DNA was extracted from manually microdissected samples from representative areas, and from frozen samples taken randomly from the same tumours. Loss of heterozygosity (LOH) of 10q23 and hypermethylation status of the PTEN promoter were studied, and the molecular findings were correlated with overall survival.

Results

PTEN protein was present heterogeneously in 42 cases and homogeneously in 18 cases. In homogeneous glioblastomas, no correlation was found between PTEN protein expression and the LOH of the gene. Surprisingly, in the heterogeneous glioblastomas, LOH was found significantly more frequently (P < 0.001) in PTEN‐positive areas (81%) than in PTEN‐negative ones (35.7%). In general, molecular results of frozen tissue were representative of the tumour. Only two cases of methylation of the PTEN promoter were identified. A significant difference was found for overall survival for LOH10q23 status (P = 0.005) and for homogeneous vs. heterogeneous tumours (P = 0.014).

Conclusion

The expression of PTEN protein does not correlate with the abnormalities of the LOH of the gene. Interestingly, patients with glioblastomas presenting either LOH of 10q23 or heterogeneous PTEN expression have a poorer prognosis.
Self‐reported sun‐related knowledge, attitudes and behaviours among schoolchildren attending South African primary schools
Authors: Wright Caradee Y. , Albers Patricia N. , Oosthuizen Maria A. , Phala Nelvia
Published: January 2014

Background

Skin cancer and other adverse health effects result from excess solar ultraviolet radiation exposure. Sun protective practices are important interventions for skin cancer prevention, particularly when implemented early in life. Several international studies have assessed children's sun‐related knowledge, attitudes and behaviours in school settings but never before in Southern Africa, where multiethnic populations exist.

Purpose

The purpose of this study is to describe the sun‐related knowledge, attitudes and behaviours as self‐reported by South African primary schoolchildren and consider the roles of sex and skin type.

Methods

A randomly selected sample of 707 schoolchildren from 24 government, urban schools in all nine provinces of South Africa were surveyed regarding their sun‐related knowledge, attitudes and behaviours.

Results

Approximately 56% of students reported experience of sunburn last summer and 59% stated that they had got a suntan. Many students (64.5%) believed that one could protect oneself from getting skin cancer by avoiding getting sunburnt. Other means reported to do so by the students were to use sunscreen (65.4%), stay out of the summer sun (48.0%), cover up with clothing (45.5%) and eat the right foods (38.0%). Only about a quarter of the students (22.4%) wrongly agreed that it is safe to get sunburnt once or twice a year. Few students (8.7%) agreed that they like to have a suntan because they feel healthier and agreed that they think a suntan makes them feel more attractive to others (17.3%). Few also agreed that most of their friends (16.1%) and family (14.2%) think that a suntan is a good thing. Children reporting to have white/light brown skin (69.4%) were more likely to agree that they used sunscreen to protect themselves from getting sunburnt compared with children having brown/dark brown/black skin (54.8%) (P = 0.0005).

Conclusion

South African schoolchildren at urban government schools do have some knowledge about sun protection, and they do have some positive sun behaviours; however, the reported occurrence of sunburn, a risk factor for skin cancer, was relatively high. There were few differences in responses by sex and some differences by skin type. These findings are important for the development of appropriate sun protection programmes aimed at schoolchildren in South Africa and other countries with similar multi‐ethnic populations.
Capital and Consumption Tax Reforms in a Small Open Economy
Authors: Chao Chi‐Chur , Yu Eden S. H.
Published: January 2014

The effects of a reform in capital and consumption taxes on private welfare and government tax revenue are examined for a small open, capital‐importing economy. A trade‐off between private welfare and tax revenue is encountered in maximizing social welfare. Nonetheless, lowering capital taxes and raising consumption taxes can increase both private welfare and tax revenue if the initial tax rates are not optimal. In addition, a tax reform by this fashion is a likely response to a rise in the foreign rate of return on capital.
Economic Determinants of Free Trade Agreements Revisited: Distinguishing Sources of Interdependence
Authors: Baier Scott L. , Bergstrand Jeffrey H. , Mariutto Ronald
Published: January 2014

One of the most notable international economic events since 1990 has been the enormous increase in the number of free trade agreements (FTAs). While Baier and Bergstrand were the first to show empirically the impact of a country‐pair's economic characteristics on the likelihood of the pair having an FTA, the literature has been extended to demonstrate the importance empirically of FTA “interdependence”—the effect of other FTAs on the probability of a pair having an FTA. In the context of the Baier–Bergstrand framework, this paper delves deeper into the sources of interdependence—an “own‐FTA” effect and a “cross‐FTA” effect. The authors argue that the own‐FTA effect (the impact on the net welfare gains of an FTA between two countries owing to either already having other FTAs) likely dwarfs the cross‐FTA effect (the impact on the net welfare gains of an FTA between the pair owing to other FTAs existing in the rest of the world, or ROW). Augmenting a parsimonious logit model with simple “multilateral FTA” and “ROW FTA” terms to differentiate the own and cross effects empirically, it is shown that the marginal impact on the probability of a country‐pair having an agreement of either country having one more FTA with a third country is 50 times that of one more FTA between another pair in ROW. The results suggest that “domino (own‐FTA) effects” have far exceeded “competitive liberalization (cross‐FTA) effects” in the proliferation of FTAs.
“Out of Sync”: The Breakdown of Economic Sentiment Cycles in the EU
Authors: Thomakos Dimitrios D. , Papailias Fotis
Published: January 2014

Empirical evidence is presented about the properties of economic sentiment cycle synchronization for Germany, France and the UK and they are compared with the “crisis” countries Italy, Spain, Portugal and Greece. Instead of using output data it is preferred to focus on the economic sentiment indicator (ESI), a forward‐looking, survey‐based variable consistently available from 1985. The cyclical nature of the ESI allowed the analyis of the presence or not of synchronicity among country pairs before and after the onset of the financial crisis. The results show that ESI movements were mostly synchronous before 2008 but they exhibit a breakdown after 2008, with this feature being more prominent in Greece. It is also found that, after the political maneuvering of the past two years, a cycle re‐integration or re‐synchronization is on the way. An analysis of the evolution of the synchronicity measures indicates that they can potentially be used to identify sudden phase breaks in ESI co‐movement and they can offer a signal as to when the EU economies are getting “in” or “out of sync”.
The Negative Effects of Privilege on Educational Attainment: Gender, Race, Class, and the Bachelor's Degree
Authors: Mangino William
Published: January 2014

Objective

To show that in the contemporary United States, traditionally privileged categories of people—men, whites, and the super‐rich—complete four‐year college degrees at rates lower than their nonprivileged counterparts—women, nonwhites, and the “99 percent.”

Methods

Logistic regression and an educational transitions method are used on the National Longitudinal Study of Adolescent Health (Waves 1 and 4) to predict, given college entrance, who completes a bachelor's degree.

Results

Women, the lower 99 percent of the income distribution, and when economic resources are present, nonwhites all complete college at higher rates than men, the richest 1 percent, and whites, respectively. In a final model, rich white men as a single category are shown to complete college less than everyone else.

Conclusion

As previously excluded categories of people have gained access to higher education, the privileged are shifting their reproduction strategies away from schooling.
Individual Activity Patterns and the Meaning of Residential Environments for Inter‐Ethnic Contact
Authors: Heringa Aafke , Bolt Gideon , Dijst Martin , van Kempen Ronald
Published: January 2014

Past research has indicated that the ethnic composition of residential neighbourhoods influences inter‐ethnic contact. However, little attention has been paid to individual activity and travel patterns which encompass encounters with others at physical and virtual activity sites, such as sports clubs and online chat rooms. By analysing a Dutch dataset on the life of urban ethnic minorities, we found that individual activity patterns are important factors in explaining inter‐ethnic contact. Activities such as sports, attending parties or religious gatherings, using Internet, and hosting friends and neighbours influence the extent of inter‐ethnic contact. The effect of ethnic composition of neighbourhoods and educational qualification on relative frequency of contact with native Dutch is strongly reduced when individual activity and travel patterns are taken into account. For receiving practical help from native Dutch, neighbourhood effects were insignificant.
Removal of biological response modifiers associated with platelet transfusion reactions by columns containing adsorption beads
Authors: Tanaka Shigenori , Hayashi Tomoya , Tani Yoshihiko , Hirayama Fumiya
Published: January 2014

Background

Biological response modifiers (BRMs), such as soluble CD40 ligand (sCD40L); regulated upon activation, normal T‐cell expressed, and secreted (RANTES); and transforming growth factor‐β1 (TGF‐β1), are released from platelets (PLTs) during storage and may trigger adverse effects after PLT transfusion. Although washing PLTs is effective at reducing the level of BRMs and the incidence of transfusion reactions, the washing procedure is time‐consuming and may induce PLT activation. Furthermore, some BRMs continue to accumulate during the storage of washed PLTs. A method to remove BRMs using adsorbent columns has not yet been developed.

Study Design and Methods

We evaluated the ability of columns packed with Selesorb and Liposorber beads, which are both clinically used, to remove BRMs from PLT concentrates (PCs) stored for 5 days. The levels of these BRMs were determined before and after adsorption.

Results

The adsorption columns significantly reduced the levels of RANTES and sCD40L and partially reduced TGF‐β1. There were no significant effects on PLT activation, aggregation, morphology, and plasma lactate dehydrogenase (an indicator of PLT lysis) levels, or hypotonic shock response. Adsorption, however, reduced the PLT recovery to approximately 60% of the untreated value.

Conclusions

This study showed that the levels of BRMs were substantially reduced using columns of clinically available adsorption beads. PLT functions and the quality of PCs were maintained after adsorption. The use of adsorption columns may be useful in reducing the incidence of nonhemolytic transfusion reactions.