bluuebunny/crossref_metadata_2025 huggingface dataset:
Conceptual Confusion: The case of Epigenetics
Authors: Pisco Angela Oliveira , Fouquier d’Hérouël Aymeric , Huang Sui
Published: May 2016

The observations of phenotypic plasticity have stimulated the revival of ‘epigenetics’. Over the past 70 years the term has come in many colors and flavors, depending on the biological discipline and time period. The meanings span from Waddington’s “epigenotype” and “epigenetic landscape” to the molecular biologists’ “epigenetic marks” embodied by DNA methylation and histone modifications. Here we seek to quell the ambiguity of the name. First we place “epigenetics” in the various historical contexts. Then, by presenting the formal concepts of dynamical systems theory we show that the “epigenetic landscape” is more than a metaphor: it has specific mathematical foundations. The latter explains how gene regulatory networks produce multiple attractor states, the self-stabilizing patterns of gene activation across the genome that account for “epigenetic memory”. This network dynamics approach replaces the reductionist correspondence of molecular epigenetic modifications with concept of the epigenetic landscape, by providing a concrete and crisp correspondence.
Deep Machine Learning provides state-of-the-art performance in image-based plant phenotyping
Authors: Pound Michael P. , Burgess Alexandra J. , Wilson Michael H. , Atkinson Jonathan A. , Griffiths Marcus , Jackson Aaron S. , Bulat Adrian , Tzimiropoulos yorgos , Wells Darren M. , Murchie Erik H. , Pridmore Tony P. , French Andrew P.
Published: May 2016

Deep learning is an emerging field that promises unparalleled results on many data analysis problems. We show the success offered by such techniques when applied to the challenging problem of image-based plant phenotyping, and demonstrate state-of-the-art results for root and shoot feature identification and localisation. We predict a paradigm shift in image-based phenotyping thanks to deep learning approaches.
3D Perception of Maximum Density Zone on Ramachandran Plots for Zika Virus Protein Structures
Authors: Mukhopadhyay Mayukh , Bhaumik Parama
Published: May 2016

The Ramachandran plot is among the most central concepts in structural biology which uses torsion angles to describe polypeptide and protein conformation. To help visualize the features of high-fidelity Ramachandran plots, it is helpful to look beyond the common two-dimensional psi-phi-plot, which for a large dataset does not serve very well to convey the true nature of the distribution. In particular, when a large subset of the observations is found very narrowly distributed within one small region, this is not well seen in the simple plot because the data points congest one another. Zika Virus (ZIKV) protein databank has been chosen as specimen for analysis. This is because the structure, tropism, and pathogenesis of ZIKV are largely unknown and are the focus of current investigations in an effort to address the need for rapid development of vaccines and therapeutics. After a brief survey on Zika Virus, it is shown that when a dense dataset of ZIKV protein databank is passed through a colour-coded scaled algorithm, a three dimensional plot gets generated which gives a much more compelling impression of the proportions of residues in the different parts of the protein rather than representing it in a normal two dimensional psi-phi plot.
The cryptic origins of evolutionary novelty: 1,000-fold-faster trophic diversification rates without increased ecological opportunity or hybrid swarm
Authors: Martin Christopher H.
Published: May 2016

Ecological opportunity is frequently proposed as the sole ingredient for adaptive radiation into novel niches. Alternatively, genome-wide hybridization resulting from ‘hybrid swarm’ may be the trigger. However, these hypotheses have been difficult to test due to the rarity of comparable control environments lacking adaptive radiations. Here I exploit such a pattern in microendemic radiations of Caribbean pupfishes. I show that a sympatric three-species radiation on San Salvador Island, Bahamas diversified 1,445 times faster than neighboring islands in jaw length due to evolution of a novel scale-eating adaptive zone from a generalist ancestral niche. I then sampled 22 generalist populations on seven neighboring islands and measured morphological diversity, stomach content diversity, dietary isotopic diversity, genetic diversity, lake/island areas, macroalgae richness, and Caribbean-wide patterns of gene flow. None of these standard metrics of ecological opportunity or gene flow were associated with adaptive radiation, except for slight increases in macroalgae richness. Thus, exceptional trophic diversification is highly localized despite myriad generalist populations in comparable environmental and genetic backgrounds. This study provides a strong counterexample to the ecological/hybrid-swarm theories of adaptive radiation and suggests that diversification of novel specialists on a sparse fitness landscape is constrained by more than ecological opportunity and gene flow.
Crystal structure and phase transition of thermoelectric SnSe
Authors: Sist Mattia , Zhang Jiawei , Brummerstedt Iversen Bo
Published: May 2016

Tin selenide-based functional materials are extensively studied in the field of optoelectronic, photovoltaic and thermoelectric devices. Specifically, SnSe has been reported to have an ultrahigh thermoelectric figure of merit of 2.6 ± 0.3 in the high-temperature phase. Here we report the evolution of lattice constants, fractional coordinates, site occupancy factors and atomic displacement factors with temperature by means of high-resolution synchrotron powder X-ray diffraction measured from 100 to 855 K. The structure is shown to be cation defective with a Sn content of 0.982 (4). The anisotropy of the thermal parameters of Sn becomes more pronounced approaching the high-temperature phase transition (∼ 810 K). Anharmonic Gram–Charlier parameters have been refined, but data from single-crystal diffraction appear to be needed to firmly quantify anharmonic features. Based on modelling of the atomic displacement parameters the Debye temperature is found to be 175 (4) K. Conflicting reports concerning the different coordinate system settings in the low-temperature and high-temperature phases are discussed. It is also shown that the high-temperatureCmcmphase is not pseudo-tetragonal as commonly assumed.
New multi-component solid forms of anti-cancer drug Erlotinib: role of auxiliary interactions in determining a preferred conformation
Authors: Sanphui Palash , Rajput Lalit , Gopi Shanmukha Prasad , Desiraju Gautam R
Published: May 2016

Erlotinib is a BCS (biopharmaceutical classification system) class II drug used for the treatment of non-small cell lung cancer. There is an urgent need to obtain new solid forms of higher solubility to improve the bioavailability of the API (active pharmaceutical ingredient). In this context, cocrystals with urea, succinic acid, and glutaric acid and salts with maleic acid, adipic acid, and saccharin were preparedviawet granulation and solution crystallizations. Crystal structures of the free base (Z′ = 2), cocrystals of erlotinib–urea (1:1), erlotinib–succinic acid monohydrate (1:1:1), erlotinib–glutaric acid monohydrate (1:1:1) and salts of erlotinib–adipic acid adipate (1:0.5:0.5) are determined and their hydrogen-bonding patterns are analyzed. Self recognitionviathe (amine) N—H...N (pyridine) hydrogen bond between the API molecules is replaced by several heterosynthons such as acid–pyridine, amide–pyridine and carboxylate–pyridinium in the new binary systems. Auxiliary interactions play an important role in determining the conformation of the API in the crystal. FT–IR spectroscopy is used to distinguish between the salts and cocrystals in the new multi-component systems. The new solid forms are characterized by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) to confirm their unique phase identity.
Hydrogen bonding at C=Se acceptors in selenoureas, selenoamides and selones
Authors: Bibelayi Dikima , Lundemba Albert S. , Allen Frank H. , Galek Peter T. A. , Pradon Juliette , Reilly Anthony M. , Groom Colin R. , Yav Zéphyrin G.
Published: May 2016

In recent years there has been considerable interest in chalcogen and hydrogen bonding involving Se atoms, but a general understanding of their nature and behaviour has yet to emerge. In the present work, the hydrogen-bonding ability and nature of Se atoms in selenourea derivatives, selenoamides and selones has been explored using analysis of the Cambridge Structural Database andab initiocalculations. In the CSD there are 70 C=Se structures forming hydrogen bonds, all of them selenourea derivatives or selenoamides. Analysis of intramolecular geometries andab initiopartial charges show that this bonding stems from resonance-induced Cδ+=Seδ−dipoles, much like hydrogen bonding to C=S acceptors. C=Se acceptors are in many respects similar to C=S acceptors, with similar vdW-normalized hydrogen-bond lengths and calculated interaction strengths. The similarity between the C=S and C=Se acceptors for hydrogen bonding should inform and guide the use of C=Se in crystal engineering.
Supramolecular hydrogen-bonding patterns of co-crystals containing the active pharmaceutical ingredient (API) phloroglucinol andN-heterocycles
Authors: Cvetkovski Aleksandar , Bertolasi Valerio , Ferretti Valeria
Published: May 2016

The active pharmaceutical ingredient phloroglucinol (PHL) has been taken as an illustrative molecule to explore the intermolecular interactions which can be established with other molecular entities to build PHL pharmaceutical co-crystals. The crystal structures of five newly synthesized co-crystals are reported, where PHL is crystallized withN-heterocycles, namely 2-hydroxy-6-methylpyridine (1), 2,4-dimethyl-6-hydroxypyrimidine (2), 4-phenylpyridine (3), 2-hydroxypyridine (4) and 2,3,5,6-tetramethylpyrazine (5). The structural characteristics of these co-crystals, as far as the hydrogen-bonding networks and the crystalline architectures are concerned, are strongly dependent on the chemical features of the coformer molecules, as well as on their size and shape. A detailed analysis of the intermolecular interactions established in all the PHL co-crystals of known structures has allowed the recognition of some regularities in the packing modes that can be useful in the design of new supramolecular adducts forming predictable structural motifs.
A new one-dimensional CdIIcoordination polymer with a two-dimensional layered structure incorporating 2-[(1H-imidazol-1-yl)methyl]-1H-benzimidazole and benzene-1,2-dicarboxylate ligands
Authors: Huang Qiu-Ying , Lin Xiao-Yi , Meng Xiang-Ru
Published: May 2016

The N-heterocyclic ligand 2-[(1H-imidazol-1-yl)methyl]-1H-benzimidazole (imb) has a rich variety of coordination modes and can lead to polymers with intriguing structures and interesting properties. In the coordination polymercatena-poly[[cadmium(II)-bis[μ-benzene-1,2-dicarboxylato-κ4O1,O1′:O2,O2′]-cadmium(II)-bis{μ-2-[(1H-imidazol-1-yl)methyl]-1H-benzimidazole}-κ2N2:N3;κ2N3:N2] dimethylformamide disolvate], {[Cd(C8H4O4)(C11H10N4)]·C3H7NO}n, (I), each CdIIion exhibits an irregular octahedral CdO4N2coordination geometry and is coordinated by four O atoms from two symmetry-related benzene-1,2-dicarboxylate (1,2-bdic2−) ligands and two N atoms from two symmetry-related imb ligands. Two CdIIions are connected by two benzene-1,2-dicarboxylate ligands to generate a binuclear [Cd2(1,2-bdic)2] unit. The binuclear units are further connected into a one-dimensional chain by pairs of bridging imb ligands. These one-dimensional chains are further connected through N—H...O hydrogen bonds and π–π interactions, leading to a two-dimensional layered structure. The dimethylformamide solvent molecules are organized in dimeric pairsviaweak interactions. In addition, the title polymer exhibits good fluorescence properties in the solid state at room temperature.
12-(3,4,5-Trimethoxyphenyl)-2,3,4,12-tetrahydro-1H-5-oxatetraphen-1-one: crystal structure and Hirshfeld surface analysis
Authors: Jotani Mukesh M. , Iniyavan P. , Vijayakumar V. , Sarveswari S. , Tan Yee Seng , Tiekink Edward R. T.
Published: May 2016

In the title compound, C26H24O5, the pyran ring has a flattened-boat conformation, with the 1,4-related ether O and methine C atoms lying 0.1205 (18) and 0.271 (2) Å, respectively, above the least-squares plane involving the doubly bonded C atoms (r.m.s deviation = 0.0208 Å). An envelope conformation is found for the cyclohexene ring, with the flap atom being the middle methylene C atom, lying 0.616 (2) Å out of the plane defined by the remaining atoms (r.m.s. deviation = 0.0173 Å). The fused four-ring system is approximately planar, with the dihedral angle between the least-squares planes through the cyclohexene and naphthyl rings being 10.78 (7)°. The trisubstituted benzene ring occupies a position almost perpendicular to the pyran ring [dihedral angle = 83.97 (4)°]. The most prominent feature of the packing is the formation of zigzag supramolecular chains mediated by aryl-C—H...O(methoxy) interactions; chains are connected into a three-dimensional architecture by methylene- and methyl-C—H...π interactions. The prevalence of C—H...O and C—H...π interactions is confirmed by an analysis of the Hirshfeld surface. A comparison with related structures suggests that the molecular conformation of the title compound is relatively robust with respect to varying substitution patterns at the methine C atom of the pyran ring.
6-Bromo-2-(4-chlorophenyl)-3-methyl-3H-imidazo[4,5-b]pyridine
Authors: Bourichi Selma , Kandri Rodi Youssef , Ouzidan Younes , Mague Joel T. , Essassi El Mokhtar , Zouihri Hafid
Published: May 2016

In the title compound, C13H9BrClN3, the imidazopyridine fused-ring system is almost planar, with r.m.s. deviation of 0.006 (19) Å, and makes a dihedral angle of 29.32 (8)° with the mean plane of the 4-chlorophenyl group. In the crystal, C—H...N hydrogen bonds link the molecules into chains propagating in the [100] direction. Weak intermolecular π–π interactions between the five- and six-membered rings of the 3H-imidazo[4,5-b]pyridine moieties of neighbouring molecules [centroid–centroid distance = 3.8648 (12) Å] further consolidate the packing into layers parallel to theabplane.
External constraints on Spanish municipal sports agencies’ finances
Authors: García-Unanue Jorge , Felipe José Luis , Gómez-González Carlos , del Corral Julio , Gallardo Leonor
Published: May 2016

Purpose

The purpose of this paper is to analyse the influence of the environment on the financial performance in public sports agencies at the local level.

Design/methodology/approach

The influence of the socio-demographic, socio-economic and political environment on the financial condition of municipal sports agencies in Spain from 2003 to 2011 was studied by several regression models.

Findings

The results show a negative influence of the size of the population and a positive influence of the municipal taxes per capita. The influence of the political context is not demonstrated. However, the set of variables only explain a small percentage of the variance.

Research limitations/implications

The main limitation of this study is the possible existence of other non-controlled environmental variables. However, this study approaches genuinely the effect of the environment on municipal sports agencies, which has important research implications as it shows additional information to be contrasted with other researches in different countries or regions.

Practical implications

The information provided in this study will be of great importance for managers to select more objectively other entities in benchmarking development.

Originality/value

Finally, this study uses a non-exploited database and redirects performance management studies to other areas of service provision such as sport.
Corporate sustainability and responsibility toward education
Authors: Camilleri Mark Anthony
Published: May 2016

Purpose

This paper aims to deliberate on how corporate social responsibility (CSR) ought to be reconceived for better educational outcomes. It suggests that there are win-win opportunities for corporations and national governments to nurture human capital and address any skill gaps and mismatches in the labour market.

Design/methodology/approach

The businesses’ involvement in setting curriculum programmes may help to improve the quality and effectiveness of extant educational systems. This contribution reports on how different organisations are already engaging in responsible behaviours with varying degrees of intensity and success across many contexts.

Findings

Many firms are often training and sponsoring individuals to pursue further studies for their career advancement. It also indicated that there are businesses that are engaging in laudable behaviours to attract prospective employees. Moreover, this paper contends that the provision of education, professional development and training will boost the employees’ morale and job satisfaction, which may, in turn, lead to lower staff turnover rates and greater productivity levels in workplace environments.

Social implications

This contribution implies that organisational cultures and their business ethos could be attuned with the governments’ educational policies to actively respond to the diverse needs of today’s learners and tomorrow’s human resources.

Originality/value

There is a business case for CSR as the corporations’ strategies realign their economic success with societal progress. Arguably, there is potential that such responsible behaviours can bring reputational benefits, enhance the firms’ image among external stakeholders and could lead to a favourable climate of trust and cooperation within the company itself.
The utilization of the double focal transformation for sparse data representation and data reconstruction
Authors: Kutscha H. , Verschuur D.J.
Published: May 2016

In many cases, seismic measurements are coarsely sampled in at least one dimension. This leads to aliasing artefacts and therefore to problems in the subsequent processing steps. To avoid this, seismic data reconstruction can be applied in advance. The success and reliability of reconstruction methods are dependent on the assumptions they make on the data. In many cases, wavefields are assumed to (locally) have a linear space–time behaviour. However, field data are usually complex, with strongly curved events. Therefore, in this paper, we propose the double focal transformation as an efficient way for complex data reconstruction. Hereby, wavefield propagation is formulated as a transformation, where one‐way propagation operators are used as its basis functions. These wavefield operators can be based on a macro velocity model, which allows our method to use prior information in order to make the data decomposition more effective. The basic principle of the double focal transformation is to focus seismic energy along source and receiver coordinates simultaneously. The seismic data are represented by a number of localized events in the focal domain, whereas aliasing noise spreads out. By imposing a sparse solution in the focal domain, aliasing noise is suppressed, and data reconstruction beyond aliasing is achieved. To facilitate the process, only a few effective depth levels need to be included, preferably along the major boundaries in the data, from which the propagation operators can be calculated. Results on 2D and 3D synthetic data illustrate the method's virtues. Furthermore, seismic data reconstruction on a 2D field dataset with gaps and aliased source spacing demonstrates the strength of the double focal transformation, particularly for near‐offset reflections with strong curvature and for diffractions.
Fast approximate 1D modelling and inversion of transient electromagnetic data
Authors: Christensen Niels B.
Published: May 2016

A novel, fast, and approximate forward modelling routine for time‐domain electromagnetic responses is presented. It is based on the separation of the forward problem into a configuration‐independent part, mapping conductivity as a function of depth onto apparent conductivity as a function of time, and a configuration‐dependent part, i.e., the half‐space step response. The response of a layered model is then found as the half‐space response for a half‐space conductivity equal to the apparent conductivity. The mapping is ten times faster than traditional accurate forward modelling routines, and through stochastic modelling, it is found that the standard deviation of the modelling error is 0.7 %. The forward mapping lends itself to integration in a modern state‐of‐the‐art inversion formulation in exactly the same way as traditionally computed responses, and a field example is included where inversion results using the approximate forward response are compared with those of an accurate forward response for helicopterborne transient electromagnetic data. In addition to being used in its own right in inversion of transient data, the speed and accuracy of the approximate inversion mean that it is well suited for quality control and fast turnaround data delivery of survey results to a client. It can also be used in hybrid inversion formulations by supplying initial iterations and high‐quality derivatives in an inversion based on accurate forward modelling.
Brexit or Bremain? Future Options for UK Agricultural Policy and the CAP
Authors: Swinbank Alan
Published: May 2016

The outcome of the UK's referendum on continued EU membership is at the time of writing uncertain, and the consequences of a vote to remain (‘Bremain’) or leave (‘Brexit’) difficult to predict. Polarised views have been voiced about the impact of Brexit on UK agriculture, and on the nature and level of funding, of future policy. Policymakers would not have the luxury of devising a new policy from scratch. WTO rules and commitments, the nature of any future accord with the EU, budget constraints, the rather different perspectives of the UK's devolved administrations in Scotland, Wales and Northern Ireland, and the expectations of farmers, landowners and the environmental lobby, will all impact the policymaking process. The WTO dimension, and the UK's future relationship with the EU, are particularly difficult to predict, and – some commentators believe – may take years to resolve. Brexit's impact on the future CAP is also unclear. A vote to remain within the EU would not necessarily assuage the Eurosceptics’ criticisms of the EU, or the UK's perception of the CAP. Whatever the outcome, future agricultural, food and rural land use policies will remain key preoccupations of European governments.
The Challenges Facing UK Farmers from Brexit
Authors: Grant Wyn
Published: May 2016

The prospect of exit from the European Union faces UK farmers with a number of additional challenges to add to those they are already coping with in terms of income and price volatility and increases the uncertainties that they face. It is difficult to predict the consequences of Brexit for agriculture with any precision, given the absence of contingency plans by the UK Government and the uncertainties that would follow a vote to leave. However, it is difficult to see that they would, on balance, be advantageous. CAP Pillar 1 farm subsidies would be placed in jeopardy and there would not be a substantial reduction in the level of regulation. The availability of plant protection products could become more restricted and firms would be reluctant to develop distinctive products purely for the UK market. Brexit would serve as a distraction from the many practical challenges facing the UK farming sector. It will not eliminate many of the structural and competitive challenges facing UK and other European farmers such as relationships with supermarkets and processors, the scale of operations and the Russian import ban.
The Religious Retinue of Leicester House: Chaplains of Frederick Louis, Prince of Wales, 1729‐51
Authors: Lees J. C.
Published: May 2016

This prosopographical study of the chaplains of Frederick Louis, prince of Wales (1707‐51), explores their political, cultural, theological and intellectual significance. It examines their dual allegiance to George II (as the Supreme Governor of the Church of England) and to Leicester House. It advances Frederick's credentials as a significant patron of the British Enlightenment and demonstrates that his clerical patronage made an important contribution to the cultural and intellectual dynamism of his rival court and to his conscious self‐fashioning as a connoisseur of the arts and as an enlightened Patriot Prince.
Family‐assisted inference of the genetic architecture of major histocompatibility complex variation
Authors: Gaigher A. , Burri R. , Gharib W. H. , Taberlet P. , Roulin A. , Fumagalli L.
Published: May 2016

With their direct link to individual fitness, genes of the major histocompatibility complex (MHC) are a popular system to study the evolution of adaptive genetic diversity. However, owing to the highly dynamic evolution of the MHC region, the isolation, characterization and genotyping of MHC genes remain a major challenge. While high‐throughput sequencing technologies now provide unprecedented resolution of the high allelic diversity observed at the MHC, in many species, it remains unclear (i) how alleles are distributed among MHC loci, (ii) whether MHC loci are linked or segregate independently and (iii) how much copy number variation (CNV) can be observed for MHC genes in natural populations. Here, we show that the study of allele segregation patterns within families can provide significant insights in this context. We sequenced two MHC class I (MHC‐I) loci in 1267 European barn owls (Tyto alba), including 590 offspring from 130 families using Illumina MiSeq technology. Coupled with a high per‐individual sequencing coverage (~3000×), the study of allele segregation patterns within families provided information on three aspects of the architecture of MHC‐I variation in barn owls: (i) extensive sharing of alleles among loci, (ii) strong linkage of MHC‐I loci indicating tandem architecture and (iii) the presence of CNV in the barn owl MHC‐I. We conclude that the additional information that can be gained from high‐coverage amplicon sequencing by investigating allele segregation patterns in families not only helps improving the accuracy of MHC genotyping, but also contributes towards enhanced analyses in the context of MHC evolutionary ecology.
Cholinergic urticaria: More than a simple inducible urticaria
Authors: Kim Hee Joo , Lee Min‐Geol
Published: May 2016

Background

Cholinergic urticaria (ChU) is characterized by small wheals induced by an elevated core temperature. Its pathomechanism and various aspects of its clinical manifestations are still poorly understood. This study aimed to evaluate the spectrum of symptoms and signs of ChU in Korean patients.

Methods

We retrospectively reviewed the medical records of patients diagnosed with ChU.

Results

Among 203 patients (188 male and 15 female), 29 (14%) complained only of an itching or burning sensation without visible skin eruption. The prevalence of ChU was highest in patients in their twenties (56%), while most patients first developed their symptoms during their teens (65%). Patients with a visible skin eruption showed better responses to antihistamines than those without skin lesions.

Conclusions

Physicians should consider the varying manifestations of ChU, including cholinergic pruritus and erythema as minor variants, to provide better management of ChU.
Haemolytic and nonhaemolytic neonatal jaundice have different risk factor profiles
Authors: Lee Brian K. , Le Ray Isabelle , Sun Ji Yu , Wikman Agneta , Reilly Marie , Johansson Stefan
Published: May 2016

Aim

This study examined maternal and pregnancy risk factors for haemolytic and nonhaemolytic neonatal jaundice in a large population‐based cohort study.

Methods

We conducted a cohort study of 1 019 220 singleton live births from the Swedish medical birth register from 1987 to 2002, using information on neonatal jaundice and maternal and pregnancy characteristics. Diagnoses of gestational hypertensive disorders were obtained by linkage to the national inpatient register. Multivariate logistic regression analysis provided odds ratios for the risk factors of both forms of jaundice.

Results

A total of 6057 (0.6%) births were affected by haemolytic jaundice and 36 869 (3.6%) by nonhaemolytic jaundice. The strongest risk factors for haemolytic jaundice were maternal alloimmunisation, blood group O and neonatal jaundice in older siblings. For nonhaemolytic jaundice, the strongest risk factors were preterm birth, neonatal jaundice in older siblings, maternal origin from East or South‐East Asia and maternal obesity. We estimated that 13% of haemolytic jaundice was attributable to alloimmunisation and 39% of nonhaemolytic jaundice was attributable to preterm birth.

Conclusion

Haemolytic and nonhaemolytic neonatal jaundice had different risk factor profiles. Interventions to reduce maternal alloimmunisation, preterm birth and maternal obesity may lower the prevalence of neonatal jaundice and the risk of consequent neurological complications.
Using the Rochester criteria to evaluate infantile fever is more effective in males than females
Authors: Dotan Miri , Ashkenazi‐Hoffnung Liat , Yarden‐Bilavsky Havazelet , Amir Jacob , Tirosh Naama , Mor Meirav , Bilavsky Efraim
Published: May 2016

Aim

The reliability of low‐risk and high‐risk criteria in evaluating febrile infants aged up to 60 days has been well documented. The aim of this study was to evaluate gender differences in the reliability of these criteria in order to exclude serious bacterial infection (SBI) in febrile infants.

Methods

This study used the Rochester risk criteria, the study group was divided into low‐ or high‐risk status for SBI, and the data were stratified by gender. SBI was defined as a urinary tract infection, bacteraemia, meningitis or bacterial enteritis.

Results

We enrolled 1896 infants (58.3% males), and SBIs were found in 10.6% of the males and 8% of the females (p = 0.21). The sensitivity of the risk criteria was 91.5% for the males and 73.4% (p < 0.05) for the females, and the positive likelihood ratio was 2.64 in the males versus 2.14 in the females (p < 0.001). A multivariable analysis showed that high‐risk male patients were more than two times more likely to develop a bacterial infection than high‐risk females.

Conclusion

The Rochester risk criteria had a significantly higher sensitivity and positive likelihood ratio in males. Our findings suggest that clinicians should take gender into account when evaluating febrile infants.
Elk‐1‐mediated 15‐lipoxygenase expression is required for hypoxia‐induced pulmonary vascular adventitial fibroblast dynamics
Authors: Li Y. , Zhang L. , Wang X. , Chen M. , Liu Y. , Xing Y. , Wang X. , Gao S. , Zhu D.
Published: May 2016

Aim

15‐Lipoxygenase (15‐LO) is an important factor in the pathogenesis of pulmonary artery hypertension (PAH). However, the role of 15‐LO in the adventitia of the pulmonary arterial wall is unclear. The aim of this study was to explore the role of 15‐LO in the modulation of pulmonary adventitial fibroblast (PAF) dynamics.

Methods

Rats were exposed to normoxic or hypoxic (fraction of inspired O2 = 0.12) treatments for 7 days. PAF proliferation and cell cycle alterations were measured by MTT assay, cell immunofluorescence, flow cytometry and Western blot analysis. The 15‐LO promoter was analysed by luciferase reporter and ChIP assays.

Results

Our results showed that hypoxia induced 15‐LO expression in PAFs both in vivo and in vitro. In addition, hypoxia stimulated JNK phosphorylation in PAFs. Blocking 15‐LO or JNK suppressed 15‐LO‐induced PAF proliferation and cell cycle alterations. The inhibition of p27kipl by gene silencing attenuated 15‐LO‐induced PAF proliferation and cell cycle alterations. Furthermore, JNK inhibition or Elk‐1 knockdown suppressed hypoxia‐induced 15‐LO expression in PAFs. Luciferase reporter and ChIP assays revealed that the 15‐LO promoter contains Elk‐1‐binding sites and also that Elk‐1 increased the hypoxia‐induced activity of the 15‐LO promoter.

Conclusion

These results suggest that hypoxia promotes changes in the cellular dynamics of PAFs by inducing 15‐LO expression, which leads to vascular adventitial remodelling. The modulation of p27kipl expression by 15‐LO enhances PAF proliferation and cell cycle alterations. Furthermore, the JNK‐dependent increase in Elk‐1 signalling is required for hypoxia‐induced 15‐LO expression in PAFs.
Potential pitfalls of serum free light chain analysis to assess treatment response for multiple myeloma
Authors: Abbi Kamal Kant Singh , Silverman Margarida , Farooq Umar , Tricot Annick , Dozeman Lindsey , Nadiminti Kalyan , Krasowski Matthew D. , Tricot Guido J.
Published: May 2016

Response to treatment in patients with a plasma cell disorder is typically measured by evaluating the bone marrow and myeloma markers, including monoclonal protein spike and immunofixation (IFE) in blood and urine, and serum free light chains (sFLCs). Stringent complete response criteria for Multiple Myeloma (MM) patients require a normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. We performed a retrospective chart review to further evaluate these criteria. A total of 142 patient charts were analysed. Of these, 17 patients were found to have an abnormal sFLC ratio, but no other evidence of disease, including normal flow cytometry and normal fluorescence in situ hybridization (FISH) analysis on highly selected plasma cells. In all patients, the abnormal sFLC ratio was caused by abnormalities in the serum kappa light chains. These results suggest that current definitions may need to be revised to take aberrancies related to abnormal immune recovery into account.
Novel relaxant effects of RPL554 on guinea pig tracheal smooth muscle contractility
Authors: Venkatasamy R , Spina D
Published: May 2016

Background and Purpose

We investigated the effectiveness of RPL554, a dual PDE3 and 4 enzyme inhibitor, on airway smooth muscle relaxation and compared it with that induced by salbutamol, ipratropium bromide, glycopyrrolate or their combination on bronchomotor tone induced by different spasmogenic agents.

Experimental Approach

Guinea pig tracheal preparations were suspended under 1 g tension in Krebs–Henseleit solution maintained at 37°C and aerated with 95% O2/5% CO2 and incubated in the presence of indomethacin (5 μM). Relaxation induced by cumulative concentrations of muscarinic receptor antagonists (ipratropium bromide or glycopyrrolate), β2‐adrenoceptor agonists (salbutamol or formoterol), PDE3 inhibitors (cilostamide, cilostazol or siguazodan) or a PDE4 inhibitor (roflumilast) was evaluated in comparison with RPL554. Maximal relaxation was calculated (% Emax papaverine) and expressed as mean ± SEM.

Key Results

Bronchomotor tone induced by the various spasmogens was reduced by the different bronchodilators to varying degrees. RPL554 (10‐300 μM) caused near maximum relaxation irrespective of the spasmogen examined, whereas the efficacy of the other relaxant agents varied according to the contractile stimulus used. During the evaluation of potential synergistic interactions between bronchodilators, RPL554 proved superior to salbutamol when either was combined with muscarinic receptor antagonists.

Conclusions and implications

RPL554 produced near maximal relaxation of highly contracted respiratory smooth muscle and provided additional relaxation compared with that produced by other clinically used bronchodilator drugs. This suggests that RPL554 has the potential to produce additional beneficial bronchodilation over and above that of maximal clinical doses of standard bronchodilators in highly constricted airways of patients.
A description of methods for deriving air pollution land use regression model predictor variables from remote sensing data in Ulaanbaatar, Mongolia
Authors: Yuchi Weiran , Knudby Anders , Cowper Joanna , Gombojav Enkhjargal , Amram Ofer , Walker Blake Byron , Allen Ryan W.
Published: May 2016

Key Messages

Air pollution is a leading risk factor for death and disease globally.

Land use regression (LUR) modelling is a commonly used exposure assessment tool, but spatially resolved data are required to generate predictor variables in LUR models.

LUR model predictors can be derived at little or no cost from satellite data and high‐resolution imagery.
CD8+T cells with distinct cytokine‐producing features and low cytotoxic activity in eosinophilic and non‐eosinophilic chronic rhinosinusitis with nasal polyps
Authors: Ma J. , Shi L.‐L. , Deng Y.‐K. , Wang H. , Cao P.‐P. , Long X.‐B. , Zhang X.‐H. , Liu Y. , Zeng M. , Liu Z.
Published: May 2016

Background

CD8+T cells are important effectors of cell‐mediated immunity; however, their contribution to the pathogenesis ofCRSis unclear.

Objective

This study aimed to characterize the cytokine‐producing features and cytotoxic activity ofCD8+T cells, and their correlation with inflammation patterns inCRSwith nasal polyps.

Methods

The expression ofIFN‐γ,IL‐4,IL‐5,IL‐17A, forkhead box P3 (FOXP3), perforin, and granzyme B inCD8+T cells was studied by means of flow cytometry, immunohistochemistry, and immunofluorescence. The expression ofCD8+T‐cell subset relevant chemokines and chemokine receptors was detected by means of real‐timeRT‐PCRorELISA. The cytotoxic activity of sortedCD8+T cells was defined by anti‐CD3‐redirected killing assay.

Results

Compared with controls, elevated percentages of totalCD8+T cells and cytotoxic T lymphocyte (Tc) 1 (IFN‐γ+), Tc2 (IL‐4+), and Tc17 (IL‐17A+) cell subset, and decreased percentages ofFOXP3+CD8+regulatory T cells, were found in both eosinophilic and non‐eosinophilic polyps with a Tc2‐skewed and Tc1/Tc17‐dominated response in eosinophilic and non‐eosinophilic polyps, respectively. NasalCD8+T cells were found to produce similar or even higher levels ofIFN‐γ andIL‐4 compared withCD4+T cells. Tc1 and Tc17, and Tc2 (IL‐4+andIL‐5+) cell subset percentages positively correlated with neutrophil and eosinophil counts in sinonasal mucosa, respectively. Strikingly, the expression of perforin and granzyme B and cytotoxic activity were significantly reduced in nasalCD8+T cells compared with their counterparts in peripheral blood. The expression ofCXCL16,CCL17, andCCL20 positively correlated with Tc1, Tc2, and Tc17 cell subset number in sinonasal mucosa, respectively.

Conclusion and Clinical Relevance

CD8+T cells have low cytotoxic activity; nevertheless, they are a significant and previously underappreciated source of inflammatory cytokine production in polyps. Different Tc cell subset domination may contribute to distinctly biased granulocyte inflammation in eosinophilic and non‐eosinophilic polyps.
Serum 25‐hydroxyvitamin D and insulin resistance in people at high risk of cardiovascular disease: a euglycaemic hyperinsulinaemic clamp study
Authors: Wallace I.R. , McKinley M.C. , McEvoy C.T. , Hamill L.L. , Ennis C.N. , McGinty A. , Bell P.M. , Patterson C.C. , Woodside J.V. , Young I.S. , Hunter S.J.
Published: May 2016

Context

In observational studies, low serum 25‐hydroxyvitamin D (25‐OHD) concentration is associated with an increased risk of type 2 diabetes mellitus (DM). Increasing serum 25‐OHD may have beneficial effects on insulin resistance or beta‐cell function. Cross‐sectional studies utilizing suboptimal methods for assessment of insulin sensitivity and serum 25‐OHD concentration provide conflicting results.

Objective

This study examined the relationship between serum 25‐OHD concentration and insulin resistance in healthy overweight individuals at increased risk of cardiovascular disease, using optimal assessment techniques.

Methods

A total of 92 subjects (mean age 56·0, SD 6·0 years), who were healthy but overweight (mean body mass index 30·9, SD 2·3 kg/m2), underwent assessments of insulin sensitivity (two‐step euglycaemic hyperinsulinaemic clamp, HOMA2‐IR), beta‐cell function (HOMA2%B), serum 25‐OHD concentration and body composition (DEXA).

Results

Mean total 25‐OHD concentration was 32·2, range 21·8–46·6 nmol/l. No association was demonstrated between serum 25‐OHD concentration and insulin resistance.

Conclusions

In this study using optimal assessment techniques to measure 25‐OHD concentration, insulin sensitivity and body composition, there was no association between serum 25‐OHD concentration and insulin resistance in healthy, overweight individuals at high risk of developing cardiovascular disease. This study suggests the documented inverse association between serum 25‐OHD concentration and risk of type 2 DM is not mediated by a relationship between serum 25‐OHD concentration and insulin resistance.
Generating spatially optimized habitat in a trade‐off between social optimality and budget efficiency
Authors: Drechsler Martin
Published: May 2016

Auctions have been proposed as alternatives to payments for environmental services when spatial interactions and costs are better known to landowners than to the conservation agency (asymmetric information). Recently, an auction scheme was proposed that delivers optimal conservation in the sense that social welfare is maximized. I examined the social welfare and the budget efficiency delivered by this scheme, where social welfare represents the difference between the monetized ecological benefit and the conservation cost incurred to the landowners and budget efficiency is defined as maximizing the ecological benefit for a given conservation budget. For the analysis, I considered a stylized landscape with land patches that can be used for agriculture or conservation. The ecological benefit was measured by an objective function that increases with increasing number and spatial aggregation of conserved land patches. I compared the social welfare and the budget efficiency of the auction scheme with an agglomeration payment, a policy scheme that considers spatial interactions and that was proposed recently. The auction delivered a higher level of social welfare than the agglomeration payment. However, the agglomeration payment was more efficient budgetarily than the auction, so the comparative performances of the 2 schemes depended on the chosen policy criterion–social welfare or budget efficiency. Both policy criteria are relevant for conservation. Which one should be chosen depends on the problem at hand, for example, whether social preferences should be taken into account in the decision of how much money to invest in conservation or whether the available conservation budget is strictly limited.
Experimental skin deposition of chromium on the hands following handling of samples of leather and metal
Authors: Bregnbak David , Thyssen Jacob P. , Jellesen Morten S. , Zachariae Claus , Johansen Jeanne D.
Published: May 2016

Background

Chromium is an important skin sensitizer. Exposure to it has been regulated in cement, and recently in leather. Studies on the deposition of chromium ions on the skin as a result of handling different chromium‐containing materials are sparse, but could improve the risk assessment of contact sensitization and allergic contact dermatitis caused by chromium.

Objectives

To determine whether the handling of chromium‐containing samples of leather and metal results in the deposition of chromium onto the skin.

Methods

Five healthy volunteers participated. For 30 min, they handled samples of leather and metal known to contain and release chromium. Skin deposition of chromium was assessed with the acid wipe sampling technique.

Results

Acid wipe sampling of the participants' fingers showed chromium deposition on the skin in all participants who had been exposed to leather (range 0.01–0.20 µg/cm2) and in 3 of 5 participants after they had manually handled metal discs (range 0.02–0.04 µg/cm2).

Conclusions

We found that samples of leather and metal had the ability to deposit chromium on the skin at significant levels, in spite of a short duration of exposure.
The Contributions of the EU Nature Directives to the CBD and Other Multilateral Environmental Agreements
Authors: Beresford Alison E. , Buchanan Graeme M. , Sanderson Fiona J. , Jefferson Rebecca , Donald Paul F.
Published: May 2016

Through a review of published studies and new analyses of publicly available data, we assess how the European Union (EU) Nature Directives complements the CBD strategic goals for 2020 as set out in the 20 Aichi Targets, thereby addressing a question posed by the European Commission about the coherence of the Directives with other international biodiversity commitments. We find evidence that the Directives complement several Aichi Targets and other Multilateral Environmental Agreements (MEAs). For example, 92% of the EU's Important Bird and Biodiversity Areas (IBAs), many of them otherwise unprotected, are partly or wholly covered by the Natura 2000 network of protected areas (contributing to Aichi Target 11). Species listed on Annex I of the Birds Directive have fared better than other species (Aichi Target 12). As 65% of EU citizens live within 5 km of a Natura 2000 site, and 98% within 20 km, these sites have the potential to raise awareness of biodiversity (Aichi Target 1) and to deliver ecosystem services to a high proportion of the EU's population (Aichi Target 14). The Nature Directives provide a regulatory framework that, with fuller implementation, will help EU Member States to meet their obligations under the CBD and other MEAs.
The Left Atrial Septal Pouch as a Possible Risk Factor for Stroke
Authors: Strachinaru Mihai , Catez Emmanuel , Jousten Iris , Pavel Oana , Janssen Christophe , Morissens Marielle , Gazagnes Marie‐Dominique
Published: May 2016

Background

The left atrial septal pouch (LASP) is formed by the caudal fusion of the area of overlap of the septum primum and the septum secundum, leaving an opening toward the left atrium. The association between LASP and stroke has not been validated by the previous studies.

Methods

The prevalence of the LASP was determined in 223 ischemic stroke patients and 223 control subjects with other cardiac pathologies, in a monocentric retrospective case–control study design. Stroke subtypes were defined according to the modified TOAST criteria.

Results

The mean age was 66 ± 15, 54% males, with a high prevalence of cardiovascular risk factors. The prevalence of the LASP was 81 (18%), irrespective of age or pathology. The number of LASP was similar in the stroke and control groups (18% vs. 19%, P = 0.7), as well as in the cryptogenic stroke subgroup (16%, P = 0.6). LASP was not associated with ischemic stroke on univariate (OR = 1.095; 95% CI = 0.676–1.772; P = 0.7) and multivariate logistic regression analysis (OR = 1.004; 95%CI = 0.574–1.758, P = 0.98). There was no statistical association between LASP and cryptogenic stroke on univariate (OR = 1.26; 95%CI = 0.526–3.016; P = 0.6) or multivariate analysis (OR = 0.705; 95%CI = 0.193–2.577, P = 0.6). The association of LASP to AF, left ventricular dysfunction, and thrombophilia did not lead to a higher incidence of stroke (OR = 0.99; 95%CI = 0.37–2.66; P = 0.99).

Conclusion

Our study did not show any association between LASP and ischemic stroke. A septal pouch was present in 18% of the population. Other associated risk factors need to be considered to incriminate the septal pouch as the etiology of a stroke.