bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of Next-Generation Sequencing for Hepatitis B Virus Resistance Testing and Genotyping in a Clinical Microbiology Laboratory
Authors: Lowe Christopher F. , Merrick Linda , Harrigan P. Richard , Mazzulli Tony , Sherlock Christopher H. , Ritchie Gordon
Published: November 2015

Sanger sequencing or DNA hybridization have been the primary modalities for hepatitis B (HBV) resistance testing and genotyping; however, there are limitations, such as low sensitivity and the inability to detect novel mutations. Next-generation sequencing (NGS) for HBV can overcome these limitations, but there is limited guidance for clinical microbiology laboratories to validate this novel technology. In this study, we describe an approach to implementing deep pyrosequencing for HBV resistance testing and genotyping in a clinical virology laboratory. A nested PCR targeting the
pol
region of HBV (codons 143 to 281) was developed, and the PCR product was sequenced by the 454 Junior (Roche). Interpretation was performed by ABL TherapyEdge based on European Association for the Study of the Liver (EASL) guidelines. Previously characterized HBV samples by INNO-LiPA (LiPA) were compared to NGS with discordant results arbitrated by Sanger sequencing. Genotyping of 105 distinct samples revealed a concordance of 95.2% (100/105), with Sanger sequencing confirming the NGS result. Resistance testing by NGS was concordant with LiPA in 85% (68/80) of previously characterized samples. Additional mutations were found in 8 samples, which related to the identification of low-level mutant subpopulations present at <10% (6/8). To balance the costs of testing for the validation study, reproducibility of the NGS was investigated through an analysis of sequence variants at loci not associated with resistance in a single patient sample. Our validation approach attempts to balance costs with efficient data acquisition.
Evaluation of a Genus- and Group-Specific Rapid PCR Assay Panel on Synovial Fluid for Diagnosis of Prosthetic Knee Infection
Authors: Melendez Dante P. , Greenwood-Quaintance Kerryl E. , Berbari Elie F. , Osmon Douglas R. , Mandrekar Jayawant N. , Hanssen Arlen D. , Patel Robin
Published: November 2015

We evaluated a genus- and group-specific PCR assay panel using 284 prosthetic knee synovial fluid samples collected from patients presenting to our institution with implant failure. Using the Musculoskeletal Infection Society diagnostic criteria, 88 and 196 samples were classified as showing prosthetic joint infection (PJI) and aseptic failure (AF), respectively. Sensitivities of the synovial fluid PCR panel and culture were 55.6% and 76.1% (
P
≤ 0.001), respectively, and specificities were 91.8% and 97.4% (
P
= 0.016), respectively. Among the 70 subjects who had received antibiotics within the month preceding synovial fluid aspiration (48 of whom had PJI), PCR panel and synovial fluid culture sensitivities were 64.5% and 85.4%, respectively (
P
< 0.0001). In this group, the PCR panel detected
Staphylococcus aureus
in two culture-negative PJI cases. Overall, the evaluated molecular diagnostic tool had low sensitivity when applied to synovial fluid.
Genome-Wide Mapping of the Binding Sites and Structural Analysis of Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 2 Reveal that It Is a DNA-Binding Transcription Factor
Authors: Hu Haidai , Dong Jiazhen , Liang Deguang , Gao Zengqiang , Bai Lei , Sun Rui , Hu Hao , Zhang Heng , Dong Yuhui , Lan Ke
Published: November 2015

The oncogenic herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is known to encode four viral interferon regulatory factors (vIRF1 to -4) to subvert the host antiviral immune response, but their detailed DNA-binding profiles as transcription factors in the host remain uncharacterized. Here, we first performed genome-wide vIRF2-binding site mapping in the human genome using chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq). vIRF2 was capable of binding to the promoter regions of 100 putative target genes. Importantly, we confirmed that vIRF2 can specifically interact with the promoters of the genes encoding PIK3C3, HMGCR, and HMGCL, which are associated with autophagosome formation or tumor progression and metastasis, and regulate their transcription
in vivo
. The crystal structure of the vIRF2 DNA-binding domain (DBD) (referred to here as vIRF2
DBD
) showed variable loop conformations and positive-charge distributions different from those of vIRF1 and cellular IRFs that are associated with DNA-binding specificities. Structure-based mutagenesis revealed that Arg82 and Arg85 are required for the
in vitro
DNA-binding activity of vIRF2
DBD
and can abolish the transcription regulation function of vIRF2 on the promoter reporter activity of
PIK3C3
,
HMGCR
, and
HMGCL
. Collectively, our study provided unique insights into the DNA-binding potency of vIRF2 and suggested that vIRF2 could act as a transcription factor of its target genes in the host antiviral immune response.

IMPORTANCE
The oncogenic herpesvirus KSHV is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. KSHV has developed a unique mechanism to subvert the host antiviral immune responses by encoding four homologues of cellular interferon regulatory factors (vIRF1 to -4). However, none of their DNA-binding profiles in the human genome have been characterized until now, and the structural basis for their diverse DNA-binding properties remain poorly understood. In this study, we performed the first genome-wide vIRF2-binding site mapping in the human genome and found vIRF2 can bind to the promoter regions of 100 target cellular genes. X-ray structure analysis and functional studies provided unique insights into its DNA-binding potency and regulation of target gene expression. Our study suggested that vIRF2 could act as a transcription factor of its target genes and contribute to KSHV infection and pathogenesis through versatile functions.
HIV-1 Vpr- and Reverse Transcription-Induced Apoptosis in Resting Peripheral Blood CD4 T Cells and Protection by Common Gamma-Chain Cytokines
Authors: Trinité Benjamin , Chan Chi N. , Lee Caroline S. , Levy David N.
Published: November 2015

HIV-1 infection leads to the progressive depletion of the CD4 T cell compartment by various known and unknown mechanisms.In vivo, HIV-1 infects both activated and resting CD4 T cells, butin vitro, in the absence of any stimuli, resting CD4 T cells from peripheral blood are resistant to infection. This resistance is generally attributed to an intracellular environment that does not efficiently support processes such as reverse transcription (RT), resulting in abortive infection. Here, we show thatin vitroHIV-1 infection of resting CD4 T cells induces substantial cell death, leading to abortive infection.In vivo, however, various microenvironmental stimuli in lymphoid and mucosal tissues provide support for HIV-1 replication. For example, common gamma-chain cytokines (CGCC), such as interleukin-7 (IL-7), render resting CD4 T cells permissible to HIV-1 infection without inducing T cell activation. Here, we find that CGCC primarily allow productive infection by preventing HIV-1 triggering of apoptosis, as evidenced by early release of cytochromecand caspase 3/7 activation. Cell death is triggered both by products of reverse transcription and by virion-borne Vpr protein, and CGCC block both mechanisms. When HIV-1 RT efficiency was enhanced by SIVmac239 Vpx protein, cell death was still observed, indicating that the speed of reverse transcription and the efficiency of its completion contributed little to HIV-1-induced cell death in this system. These results show that a major restriction on HIV-1 infection in resting CD4 T cells resides in the capacity of these cells to survive the early steps of HIV-1 infection.

IMPORTANCEA major consequence of HIV-1 infection is the destruction of CD4 T cells. Here, we show that delivery of virion-associated Vpr protein and the process of reverse transcription are each sufficient to trigger apoptosis of resting CD4 T cells isolated from peripheral blood. While these 2 mechanisms have been previously described in various cell types, we show for the first time their concerted effect in inducing resting CD4 T cell depletion. Importantly, we found that cytokines such as IL-7 and IL-4, which are particularly active in sites of HIV-1 replication, protect resting CD4 T cells from these cytopathic effects and, primarily through this protection, rather than through enhancement of specific replicative steps, they promote productive infection. This study provides important new insights for the understanding of the early steps of HIV-1 infection and T cell depletion.
Functional Characterization of the Serine-Rich Tract of Varicella-Zoster Virus IE62
Authors: Kim Seong K. , Shakya Akhalesh K. , Kim Seongman , O'Callaghan Dennis J.
Published: November 2015

The immediate early 62 protein (IE62) of varicella-zoster virus (VZV), a major viral
trans
-activator, initiates the virus life cycle and is a key component of pathogenesis. The IE62 possesses several domains essential for
trans
-activation, including an acidic
trans
-activation domain (TAD), a serine-rich tract (SRT), and binding domains for USF, TFIIB, and TATA box binding protein (TBP). Transient-transfection assays showed that the VZV IE62 lacking the SRT
trans
-activated the early VZV ORF61 promoter at only 16% of the level of the full-length IE62. When the SRT of IE62 was replaced with the SRT of equine herpesvirus 1 (EHV-1) IEP, its
trans
-activation activity was completely restored. Herpes simplex virus 1 (HSV-1) ICP4 that lacks a TAD very weakly (1.5-fold)
trans
-activated the ORF61 promoter. An IE62 TAD-ICP4 chimeric protein exhibited
trans
-activation ability (10.2-fold), indicating that the IE62 TAD functions with the SRT of HSV-1 ICP4 to
trans
-activate viral promoters. When the serine and acidic residues of the SRT were replaced with Ala, Leu, and Gly,
trans
-activation activities of the modified IE62 proteins IE62-SRTΔSe and IE62-SRTΔAc were reduced to 46% and 29% of wild-type activity, respectively. Bimolecular complementation assays showed that the TAD of IE62, EHV-1 IEP, and HSV-1 VP16 interacted with Mediator 25 in human melanoma MeWo cells. The SRT of IE62 interacted with the nucleolar-ribosomal protein EAP, which resulted in the formation of globular structures within the nucleus. These results suggest that the SRT plays an important role in VZV viral gene expression and replication.

IMPORTANCE
The immediate early 62 protein (IE62) of varicella-zoster virus (VZV) is a major viral
trans
-activator and is essential for viral growth. Our data show that the serine-rich tract (SRT) of VZV IE62, which is well conserved within the alphaherpesviruses, is needed for
trans
-activation mediated by the acidic
trans
-activation domain (TAD). The TADs of IE62, EHV-1 IEP, and HSV-1 VP16 interacted with cellular Mediator 25 in bimolecular complementation assays. The interaction of the IE62 SRT with nucleolar-ribosomal protein EAP resulted in the formation of globular structures within the nucleus. Understanding the mechanisms by which the TAD and SRT of IE62 contribute to the function of this essential regulatory protein is important in understanding the gene program of this human pathogen.
Identification of an HIV-1 Mutation in Spacer Peptide 1 That Stabilizes the Immature CA-SP1 Lattice
Authors: Fontana Juan , Keller Paul W. , Urano Emiko , Ablan Sherimay D. , Steven Alasdair C. , Freed Eric O.
Published: November 2015

Upon release of HIV-1 particles from the infected cell, the viral protease cleaves the Gag polyprotein at specific sites, triggering maturation. During this process, which is essential for infectivity, the capsid protein (CA) reassembles into a conical core. Maturation inhibitors (MIs) block HIV-1 maturation by interfering with protease-mediated CA-spacer peptide 1 (CA-SP1) processing, concomitantly stabilizing the immature CA-SP1 lattice; virions from MI-treated cells retain an immature-like CA-SP1 lattice, whereas mutational abolition of cleavage at the CA-SP1 site results in virions in which the CA-SP1 lattice converts to a mature-like form. We previously reported that propagation of HIV-1 in the presence of MI PF-46396 selected for assembly-defective, compound-dependent mutants with amino acid substitutions in the major homology region (MHR) of CA. Propagation of these mutants in the absence of PF-46396 resulted in the acquisition of second-site compensatory mutations. These included a Thr-to-Ile substitution at SP1 residue 8 (T8I), which results in impaired CA-SP1 processing. Thus, the T8I mutation phenocopies PF-46396 treatment in terms of its ability to rescue the replication defect imposed by the MHR mutations and to impede CA-SP1 processing. Here, we use cryo-electron tomography to show that, like MIs, the T8I mutation stabilizes the immature-like CA-SP1 lattice. These results have important implications for the mechanism of action of HIV-1 MIs; they also suggest that T8I may provide a valuable tool for structural definition of the CA-SP1 boundary region, which has thus far been refractory to high-resolution analysis, apparently because of conformational flexibility in this region of Gag.

IMPORTANCE
HIV-1 maturation involves dissection of the Gag polyprotein by the viral protease and assembly of a conical capsid enclosing the viral ribonucleoprotein. Maturation inhibitors (MIs) prevent the final cleavage step at the site between the capsid protein (CA) and spacer peptide 1 (SP1), apparently by binding at this site and denying the protease access. Additionally, MIs stabilize the immature-like CA-SP1 lattice, preventing release of CA into the soluble pool. We previously found that T8I, a mutation in SP1, rescues a PF-46396-dependent CA mutant and blocks CA-SP1 cleavage. In this study, we imaged T8I virions by cryo-electron tomography and showed that T8I mutants, like MI-treated virions, contain an immature CA-SP1 lattice. These results lay the groundwork needed to understand the structure of the CA-SP1 interface region and further illuminate the mechanism of action of MIs.
Structural Studies of Chikungunya Virus-Like Particles Complexed with Human Antibodies: Neutralization and Cell-to-Cell Transmission
Authors: Porta Jason , Mangala Prasad Vidya , Wang Cheng-I , Akahata Wataru , Ng Lisa F. P. , Rossmann Michael G.
Published: November 2015

Chikungunya virus is a positive-stranded RNA alphavirus. Structures of chikungunya virus-like particles in complex with strongly neutralizing antibody Fab fragments (8B10 and 5F10) were determined using cryo-electron microscopy and X-ray crystallography. By fitting the crystallographically determined structures of these Fab fragments into the cryo-electron density maps, we show that Fab fragments of antibody 8B10 extend radially from the viral surface and block receptor binding on the E2 glycoprotein. In contrast, Fab fragments of antibody 5F10 bind the tip of the E2 B domain and lie tangentially on the viral surface. Fab 5F10 fixes the B domain rigidly to the surface of the virus, blocking exposure of the fusion loop on glycoprotein E1 and therefore preventing the virus from becoming fusogenic. Although Fab 5F10 can neutralize the wild-type virus, it can also bind to a mutant virus without inhibiting fusion or attachment. Although the mutant virus is no longer able to propagate by extracellular budding, it can, however, enter the next cell by traveling through junctional complexes without being intercepted by a neutralizing antibody to the wild-type virus, thus clarifying how cell-to-cell transmission can occur.

IMPORTANCE
Alphaviral infections are transmitted mainly by mosquitoes. Chikungunya virus (CHIKV), which belongs to the
Alphavirus
genus, has a wide distribution in the Old World that has expanded in recent years into the Americas. There are currently no vaccines or drugs against alphaviral infections. Therefore, a better understanding of CHIKV and its associated neutralizing antibodies will aid in the development of effective treatments.
Structural Insights into HIV-1 Vif-APOBEC3F Interaction
Authors: Nakashima Masaaki , Ode Hirotaka , Kawamura Takashi , Kitamura Shingo , Naganawa Yuriko , Awazu Hiroaki , Tsuzuki Shinya , Matsuoka Kazuhiro , Nemoto Michiko , Hachiya Atsuko , Sugiura Wataru , Yokomaku Yoshiyuki , Watanabe Nobuhisa , Iwatani Yasumasa
Published: November 2015

The HIV-1 Vif protein inactivates the cellular antiviral cytidine deaminase APOBEC3F (A3F) in virus-infected cells by specifically targeting it for proteasomal degradation. Several studies identified Vif sequence motifs involved in A3F interaction, whereas a Vif-binding A3F interface was proposed based on our analysis of highly similar APOBEC3C (A3C). However, the structural mechanism of specific Vif-A3F recognition is still poorly understood. Here we report structural features of interaction interfaces for both HIV-1 Vif and A3F molecules. Alanine-scanning analysis of Vif revealed that six residues located within the conserved Vif F1-, F2-, and F3-box motifs are essential for both A3C and A3F degradation, and an additional four residues are uniquely required for A3F degradation. Modeling of the Vif structure on an HIV-1 Vif crystal structure revealed that three discontinuous flexible loops of Vif F1-, F2-, and F3-box motifs sterically cluster to form a flexible A3F interaction interface, which represents hydrophobic and positively charged surfaces. We found that the basic Vif interface patch (R17, E171, and R173) involved in the interactions with A3C and A3F differs. Furthermore, our crystal structure determination and extensive mutational analysis of the A3F C-terminal domain demonstrated that the A3F interface includes a unique acidic stretch (L291, A292, R293, and E324) crucial for Vif interaction, suggesting additional electrostatic complementarity to the Vif interface compared with the A3C interface. Taken together, these findings provide structural insights into the A3F-Vif interaction mechanism, which will provide an important basis for development of novel anti-HIV-1 drugs using cellular cytidine deaminases.

IMPORTANCE
HIV-1 Vif targets cellular antiviral APOBEC3F (A3F) enzyme for degradation. However, the details on the structural mechanism for specific A3F recognition remain unclear. This study reports structural features of interaction interfaces for both HIV-1 Vif and A3F molecules. Three discontinuous sequence motifs of Vif, F1, F2, and F3 boxes, assemble to form an A3F interaction interface. In addition, we determined a crystal structure of the wild-type A3F C-terminal domain responsible for the Vif interaction. These results demonstrated that both electrostatic and hydrophobic interactions are the key force driving Vif-A3F binding and that the Vif-A3F interfaces are larger than the Vif-A3C interfaces. These findings will allow us to determine the configurations of the Vif-A3F complex and to construct a structural model of the complex, which will provide an important basis for inhibitor development.
Differential Recognition of Influenza A Viruses by M158–66Epitope-Specific CD8+T Cells Is Determined by Extraepitopic Amino Acid Residues
Authors: van de Sandt Carolien E. , Kreijtz Joost H. C. M. , Geelhoed-Mieras Martina M. , Nieuwkoop Nella J. , Spronken Monique I. , van de Vijver David A. M. C. , Fouchier Ron A. M. , Osterhaus Albert D. M. E. , Rimmelzwaan Guus F.
Published: November 2015

Natural influenza A virus infections elicit both virus-specific antibody and CD4+and CD8+T cell responses. Influenza A virus-specific CD8+cytotoxic T lymphocytes (CTLs) contribute to clearance of influenza virus infections. Viral CTL epitopes can display variation, allowing influenza A viruses to evade recognition by epitope-specific CTLs. Due to functional constraints, some epitopes, like the immunodominant HLA-A*0201-restricted matrix protein 1 (M158–66) epitope, are highly conserved between influenza A viruses regardless of their subtype or host species of origin. We hypothesized that human influenza A viruses evade recognition of this epitope by impairing antigen processing and presentation by extraepitopic amino acid substitutions. Activation of specific T cells was used as an indication of antigen presentation. Here, we show that the M158–66epitope in the M1 protein derived from human influenza A virus was poorly recognized compared to the M1 protein derived from avian influenza A virus. Furthermore, we demonstrate that naturally occurring variations at extraepitopic amino acid residues affect CD8+T cell recognition of the M158–66epitope. These data indicate that human influenza A viruses can impair recognition by M158–66-specific CTLs while retaining the conserved amino acid sequence of the epitope, which may represent a yet-unknown immune evasion strategy for influenza A viruses. This difference in recognition may have implications for the viral replication kinetics in HLA-A*0201 individuals and spread of influenza A viruses in the human population. The findings may aid the rational design of universal influenza vaccines that aim at the induction of cross-reactive virus-specific CTL responses.

IMPORTANCEInfluenza viruses are an important cause of acute respiratory tract infections. Natural influenza A virus infections elicit both humoral and cellular immunity. CD8+cytotoxic T lymphocytes (CTLs) are directed predominantly against conserved internal proteins and confer cross-protection, even against influenza A viruses of various subtypes. In some CTL epitopes, mutations occur that allow influenza A viruses to evade recognition by CTLs. However, the immunodominant HLA-A*0201-restricted M158–66epitope does not tolerate mutations without loss of viral fitness. Here, we describe naturally occurring variations in amino acid residues outside the M158–66epitope that influence the recognition of the epitope. These results provide novel insights into the epidemiology of influenza A viruses and their pathogenicity and may aid rational design of vaccines that aim at the induction of CTL responses.
Correlation between Virus Replication and Antibody Responses in Macaques following Infection with Pandemic Influenza A Virus
Authors: Koopman Gerrit , Mooij Petra , Dekking Liesbeth , Mortier Daniëlla , Nieuwenhuis Ivonne G. , van Heteren Melanie , Kuipers Harmjan , Remarque Edmond J. , Radošević Katarina , Bogers Willy M. J. M.
Published: November 2015

Influenza virus infection of nonhuman primates is a well-established animal model for studying pathogenesis and for evaluating prophylactic and therapeutic intervention strategies. However, usually a standard dose is used for the infection, and there is no information on the relation between challenge dose and virus replication or the induction of immune responses. Such information is also very scarce for humans and largely confined to evaluation of attenuated virus strains. Here, we have compared the effect of a commonly used dose (4 × 10
6
50% tissue culture infective doses) versus a 100-fold-higher dose, administered by intrabronchial installation, to two groups of 6 cynomolgus macaques. Animals infected with the high virus dose showed more fever and had higher peak levels of gamma interferon in the blood. However, virus replication in the trachea was not significantly different between the groups, although in 2 out of 6 animals from the high-dose group it was present at higher levels and for a longer duration. The virus-specific antibody response was not significantly different between the groups. However, antibody enzyme-linked immunosorbent assay, virus neutralization, and hemagglutination inhibition antibody titers correlated with cumulative virus production in the trachea. In conclusion, using influenza virus infection in cynomolgus macaques as a model, we demonstrated a relationship between the level of virus production upon infection and induction of functional antibody responses against the virus.

IMPORTANCE
There is only very limited information on the effect of virus inoculation dose on the level of virus production and the induction of adaptive immune responses in humans or nonhuman primates. We found only a marginal and variable effect of virus dose on virus production in the trachea but a significant effect on body temperature. The induction of functional antibody responses, including virus neutralization titer, hemagglutination inhibition titer, and antibody-dependent cell-mediated cytotoxicity, correlated with the level of virus replication measured in the trachea. The study reveals a relationship between virus production and functional antibody formation, which could be relevant in defining appropriate criteria for new influenza virus vaccine candidates.
Spore Germination
Authors: Moir Anne , Cooper Gareth
Published: November 2015

Despite being resistant to a variety of environmental insults, the bacterial endospore can sense the presence of small molecules and respond by germinating, losing the specialized structures of the dormant spore, and resuming active metabolism, before outgrowing into vegetative cells. Our current level of understanding of the spore germination process in bacilli and clostridia is reviewed, with particular emphasis on the germinant receptors characterized in
Bacillus subtilis
,
Bacillus cereus
, and
Bacillus anthracis
. The recent evidence for a local clustering of receptors in a “germinosome” would begin to explain how signals from different receptors could be integrated. The SpoVA proteins, involved in the uptake of Ca
2+
-dipicolinic acid into the forespore during sporulation, are also responsible for its release during germination. Lytic enzymes SleB and CwlJ, found in bacilli and some clostridia, hydrolyze the spore cortex: other clostridia use SleC for this purpose. With genome sequencing has come the appreciation that there is considerable diversity in the setting for the germination machinery between bacilli and clostridia.
Exposure to secondhand smoke from neighbours and respiratory symptoms in never-smoking adolescents in Hong Kong: a cross-sectional study
Authors: Leung Lok Tung , Ho Sai Yin , Wang Man Ping , Lo Wing Sze , Lam Tai Hing
Published: November 2015

Objectives

To investigate secondhand smoke (SHS) exposure at home from neighbours in Hong Kong adolescents and its association with respiratory symptoms in never-smokers.

Design

A cross-sectional study.

Setting

79 randomly selected secondary schools in Hong Kong.

Participants

61 810 secondary 1 (USA grade 7) to 7 students, in which 50 762 never-smokers were identified and included in the analysis of the association between SHS exposure at home from neighbours and respiratory symptoms.

Main outcome measures

Smoking status, family smoking status, SHS exposure at home from inside the home and from neighbours in the past 7 days, respiratory symptoms and sociodemographic characteristics were reported. Adjusted ORs (AORs) of respiratory symptoms for SHS exposure from the 2 sources in never-smokers were calculated using logistic regression.

Results

In all students, 33.2% were exposed to SHS at home, including 16.2% from inside the home only, 10.0% from neighbours only and 7.0% from both. The prevalence of SHS exposure from neighbours was 17.1%, including 13.5% for 1–4 days/week and 3.6% for 5–7 days/week. In never-smokers (n=50 762), respiratory symptoms were significantly associated with SHS exposure from neighbours with AORs (95% CI) of 1.29 (1.20 to 1.39) for any exposure (p<0.001), 1.21 (1.12 to 1.31) for 1–4 days/week (p<0.001) and 1.63 (1.44 to 1.86) for 5–7 days/week (p<0.001) (P for trend <0.001). Compared with no SHS exposure at home from any source, the AORs were 1.16 (1.07 to 1.25) for SHS from inside the home only (p<0.001), 1.20 (1.11 to 1.31) from neighbours only (p<0.001), and 1.74 (1.56 to 1.94) from both (p<0.001).

Conclusions

SHS exposure at home from neighbours was prevalent in Hong Kong adolescents, and was associated with respiratory symptoms in never-smokers. SHS exposure at home may be underestimated by ignoring the neighbouring source. Smoke-free housing policy is needed to protect children and adolescents from harms of SHS.
Supervised pharmacy student-led medication review in primary care for patients with type 2 diabetes: a randomised controlled pilot study
Authors: Adams R P , Barton G , Bhattacharya D , Grassby P F , Holland R , Howe A , Norris N , Shepstone L , Wright D J
Published: November 2015

Objective

To pilot and feasibility-test supervised final year undergraduate pharmacy student-led medication reviews for patients with diabetes to enable definitive trial design.

Method

Third year pharmacy students were recruited from one UK School of Pharmacy and trained to review patient's medical records and provide face-to-face consultations under supervision while situated within the patient's medical practice. Patients with type 2 diabetes were recruited by postal invitation letter from their medical practice and randomised via automated system to intervention or usual care. Diabetes-related clinical data, quality of life, patient reported beliefs, adherence and satisfaction with medicines information were collected with validated tools at baseline and 6 months postintervention. The process for collecting resource utilisation data was tested. Stakeholder meetings were held before and after intervention to develop study design and learn from its implementation. Recruitment and attrition rates were determined plus the quality of the outcome data. Power calculations for a definitive trial were performed on the different outcome measures to identify the most appropriate primary outcome measure.

Results

792 patients were identified as eligible from five medical practices. 133 (16.8%) were recruited and randomised to control (n=66) or usual care (n=67). 32 students provided the complete intervention to 58 patients. Initial data analysis showed potential for impact in the right direction for some outcomes measured including glycated haemoglobin, quality of life and patient satisfaction with information about medicines. The intervention was found to be feasible and acceptable to patients. The pilot and feasibility study enabled the design of a future full randomised controlled trial.

Conclusions

Student and patient recruitment are possible. The intervention was well received and demonstrated some potential benefits. While the intervention was relatively inexpensive and provided an experiential learning opportunity for pharmacy students, its cost-effectiveness remains to be determined.

Trial registration number

ISRCTN26445805; Results.
Republished: Solitaire salvage: a stent retriever-assisted catheter reduction technical report
Authors: Parry Phillip Vaughan , Morales Alejandro , Jankowitz Brian Thomas
Published: November 2015

The endovascular management of giant aneurysms often proves difficult with standard techniques. Obtaining distal access to allow catheter reduction is often key to approaching these aneurysms, but several anatomic challenges make this task unsafe and not feasible. Obtaining distal anchor points and performing catheter reduction maneuvers using adjunctive devices is not a novel concept, however using the Solitaire in order to do so may have some distinct advantages compared with previously described methods. Here we describe our novel Solitaire salvage technique, which allowed successful reduction of a looped catheter within an aneurysm in three cases. While this technique is expensive and therefore best performed after standard maneuvers have failed, in our experience it was effective, safe, and more efficient than other methods.
Second‐year student diary
Authors: Perrett Rosie
Published: November 2015

Rosie Perrett is back in the swing of things at Liverpool vet school.
The rise of the referral sector
Authors: White Dick
Published: November 2015

The private referral sector in the UK has grown rapidly over the past 20 years. Continuing Veterinary Record's series of articles discussing the state of different sectors of the veterinary profession, Dick White considers how the sector has evolved and how it might continue to develop
Seasonality affects phytotoxic potential of five native species of Neotropical savanna
Authors: Pinto Graciele Fernanda de Souza , Kolb Rosana Marta
Published: November 2015

Phytotoxic secondary metabolites produced by plants have been studied as possible sources of bioherbicides. However, several environmental factors can change the secondary metabolism of plants, and thus, the production of these compounds. Among these factors, seasonality can be a source of variation in the content of all classes of secondary metabolites. In this study, we evaluated the phytotoxic effect of aqueous extracts of leaves from Byrsonima intermedia A. Juss. (Malpighiaceae), Gochnatia polymorpha (Less.) Cabrera (Asteraceae), Luehea candicans Mart. (Tiliaceae), Miconia chamissois Naudin (Melastomataceae), and Qualea cordata Spreng (Vochysiaceae) (species of the Brazilian savanna), collected both during the dry and the rainy season, on germination and seedling growth of maize and cucumber. The analysed parameters were affected by all leaf extracts collected during both seasons. However, a greater phytotoxic effect was observed when leaves were collected during the dry or during the rainy season, depending on the savanna species studied, on the target species, and on the parameters evaluated. The phytochemical screening of all extracts was also evaluated and allowed the identification of anthraquinones, triterpenoids, saponins, and tannins. The composition of extracts differed between the seasons for all species. This study highlights the importance of considering savanna seasonality when studying the phytotoxicity of the species of this biome.
A Two-Stage Combining Classifier Model for the Development of Adaptive Dialog Systems
Authors: Griol David , Iglesias José Antonio , Ledezma Agapito , Sanchis Araceli
Published: November 2015

This paper proposes a statistical framework to develop user-adapted spoken dialog systems. The proposed framework integrates two main models. The first model is used to predict the user’s intention during the dialog. The second model uses this prediction and the history of dialog up to the current moment to predict the next system response. This prediction is performed with an ensemble-based classifier trained for each of the tasks considered, so that a better selection of the next system can be attained weighting the outputs of these specialized classifiers. The codification of the information and the definition of data structures to store the data supplied by the user throughout the dialog makes the estimation of the models from the training data and practical domains manageable. We describe our proposal and its application and detailed evaluation in a practical spoken dialog system.
Mixed integral identities involving unit spheres and balls in complex context
Authors: Oliveira C. P. , Buescu Jorge
Published: November 2015

In this paper, we derive integral identities relating both unit spheres and unit balls of several dimensions in the complex setting. More specifically, we find a chain of equations involving either balls or balls and spheres of different dimensions. In addition, as a result almost independent we prove a prototype of the Funk–Hecke formula for embedded subspheres within the unit sphere of [Formula: see text], allowing for a closed-form expression for the computation of the eigenvalues.
THE GREAT TRANSITION: IMPLICATIONS FROM ENVIRONMENTAL POLICY FOR THE QUALITY–QUANTITY TRADE-OFF IN CHILDREN-REARING
Authors: TOURNEMAINE FREDERIC , TSOUKIS CHRISTOPHER
Published: November 2015

We develop an overlapping-generations model with human capital accumulation and endogenous fertility containing a pollution externality. We study the effects of an environmental policy on individuals’ quality–quantity trade-off on children. In a Malthusian poverty trap, we show that a more stringent policy induces a reduction of fertility. In a state of perpetual development, we find a similar result and show that higher environmental quality, growth and welfare are compatible goals. Moreover, we show that the policy can be used as an instrument for initiating a country’s great transition from a state of poverty to a state of development.
Jet energy calibration at the LHC
Authors: Schwartzman Ariel
Published: November 2015

Jets are one of the most prominent physics signatures of high energy proton–proton (p–p) collisions at the Large Hadron Collider (LHC). They are key physics objects for precision measurements and searches for new phenomena. This review provides an overview of the reconstruction and calibration of jets at the LHC during its first Run. ATLAS and CMS developed different approaches for the reconstruction of jets, but use similar methods for the energy calibration. ATLAS reconstructs jets utilizing input signals from their calorimeters and use charged particle tracks to refine their energy measurement and suppress the effects of multiple p–p interactions (pileup). CMS, instead, combines calorimeter and tracking information to build jets from particle flow objects. Jets are calibrated using Monte Carlo (MC) simulations and a residual in situ calibration derived from collision data is applied to correct for the differences in jet response between data and Monte Carlo. Large samples of dijet, [Formula: see text]+jets, and [Formula: see text]+events at the LHC allowed the calibration of jets with high precision, leading to very small systematic uncertainties. Both ATLAS and CMS achieved a jet energy calibration uncertainty of about 1% in the central detector region and for jets with transverse momentum [Formula: see text]. At low jet [Formula: see text], the jet energy calibration uncertainty is less than 4%, with dominant contributions from pileup, differences in energy scale between quark and gluon jets, and jet flavor composition.
Search for physics beyond the Standard Model using jet observables
Authors: Kousouris Konstantinos
Published: November 2015

Jet observables have been exploited extensively during the LHC Run 1 to search for physics beyond the Standard Model. In this article, the most recent results from the ATLAS and CMS collaborations are summarized. Data from proton–proton collisions at 7 and 8 TeV center-of-mass energy have been analyzed to study monojet, dijet, and multijet final states, searching for a variety of new physics signals that include colored resonances, contact interactions, extra dimensions, and supersymmetric particles. The exhaustive searches with jets in Run 1 did not reveal any signal, and the results were used to put stringent exclusion limits on the new physics models.
A review and analysis on growth and optical absorption properties of silicon nanowire array for photovoltaic applications
Authors: Sharma Ritu , Dusad Lalit Kumar
Published: November 2015

In this paper, optical absorptions in silicon nanowires (SiNWs) arrays obtained from theoretical studies and experimental approaches have been reviewed. A brief description on the different growth techniques for SiNW arrays reported so far is presented. Comparative analysis based on major research findings has been done and the advantages of SiNW-based solar cells over thin film solar cells are presented. Furthermore, future aspects of the use of SiNWs for photovoltaic applications are discussed.
Exploring social influence on evolutionary prisoner’s dilemma games in networks
Authors: Zong Hengshan , Jia Guozhu , Cheng Yang
Published: November 2015

Though numerous studies demonstrate the importance of social influence in deciding individual decision-making process in networks, little has been done to explore its impact on players’ behavioral patterns in evolutionary prisoner’s dilemma games (PDGs). This study investigates how social influenced strategy updating rules may affect the final equilibrium of game dynamics. The results show that weak social influence usually inhibits cooperation, while strong social influence has a mediating effect. The impacts of network structure and the existence of rebels in social influence scenarios are also tested. The paper provides a comprehensive interpretation on social influence effects on evolutionary PDGs in networks.
Crystallization process and magnetic property of Fe81Zr3Nb6B10 alloy
Authors: Sun Y. M. , Yu W. Q. , Long D. , Zhang Y. , Hua Z.
Published: November 2015

[Formula: see text] amorphous alloy was prepared by melt-spinning and annealed at various temperatures. The thermal property, microstructure and magnetic property were investigated by differential thermal analysis (DTA), X-ray diffraction (XRD) and vibrating sample magnetometer (VSM). The crystallization process of [Formula: see text] alloy is as follow: Amorphous [Formula: see text] residual amorphous [Formula: see text]-[Formula: see text]-[Formula: see text]-[Formula: see text] solid solution. Coercivity [Formula: see text] of [Formula: see text] alloy changes complexly, which abruptly deteriorates at 843 K and then softens with increasing annealing temperature [Formula: see text].
Optical spectrum evolution induced by altering input light wavelength spacing
Authors: Wang Minjie , Ma Caiwen
Published: November 2015

This study explored the optical spectrum evolution process using a pump-modulated light and a continuous-wave probe, launched simultaneously into a 1 km highly nonlinear fiber. A total of 70 optical spectra were obtained by each changing the wavelength spacing (0.4 nm) between the probe and pump lights. Simulation results indicated that wavelength spacing between the two beams caused a cyclical optical spectrum evolution process induced by cross-phase modulation. As input light wavelength spacing increased, the coupling between the two optical fields showed obvious attenuation in each neat, multi-peak cycle.
Finite convergent presentation of plactic monoid for type C
Authors: Hage Nohra
Published: November 2015

We give an explicit presentation for the plactic monoid for type C using admissible column generators. Thanks to the combinatorial properties of symplectic tableaux, we prove that this presentation is finite and convergent. We obtain as a corollary that plactic monoids for type C satisfy homological finiteness properties.
Decision Theory, an Unprecedented Validation Scheme for Rough-Fuzzy Clustering
Authors: Revathy S. , Parvathavarthini B. , Caroline S. Shiny
Published: November 2015

Cluster validation is an essential technique in all cluster applications. Several validation methods measure the accuracy of cluster structure. Typical methods are geometric, where only distance and membership form the core of validation. Yao's decision theory is a novel approach for cluster validation, which evolved loss calculations and probabilistic based measure for determining the cluster quality. Conventional rough set algorithms have utilized this validity measure. This paper propagates decision theory, an unprecedented validation scheme for Rough-Fuzzy clustering by resolving loss and probability calculations to predict the risk measure in clustering techniques. Experiments with synthetic and UCI datasets have been performed, proven to deduce the optimal number of clusters overcoming the downsides of traditional validation frameworks. The proposed index can also be applied to other clustering algorithms and extends the usefulness in business oriented data mining.
An Integrated Hybrid Algorithm Based on Nature Inspired Evolutionary for Radial Basis Function Neural Network Learning
Authors: Chen Zhen-Yao , Kuo R. J. , Hu Tung-Lai
Published: November 2015

This paper intends to propose an integrated hybrid algorithm for training radial basis function neural network (RBFNN) learning. The proposed integrated of particle swarm and genetic algorithm based optimization (IPGO) algorithm is composed of two approaches based on particle swarm optimization (PSO) and genetic algorithm (GA) for gathering both their virtues to improve the learning performance of RBFNN. The diversity of individuals results in higher chance to search in the direction of global optimal instead of being confined to local optimal particularly in problem with higher complexity. The IPGO algorithm with PSO-based and GA-based approaches has shown promising results in some benchmark problems with three continuous test functions. After proposing the algorithm for these problems with result providing its outperforming performance, this paper supplements a practical application case for the papaya milk sales forecasting to expound the superiority of the IPGO algorithm. In addition, model evaluation results of the case have showed that the IPGO algorithm outperforms other algorithms and auto-regressive moving average (ARMA) models in terms of forecasting accuracy and execution time.
Groups all of whose undirected Cayley graphs are determined by their spectra
Authors: Abdollahi Alireza , Janbaz Shahrooz , Jazaeri Mojtaba
Published: November 2015

The adjacency spectrum [Formula: see text] of a graph [Formula: see text] is the multiset of eigenvalues of its adjacency matrix. Two graphs with the same spectrum are called cospectral. A graph [Formula: see text] is “determined by its spectrum” (DS for short) if every graph cospectral to it is in fact isomorphic to it. A group is DS if all of its Cayley graphs are DS. A group [Formula: see text] is Cay-DS if every two cospectral Cayley graphs of [Formula: see text] are isomorphic. In this paper, we study finite DS groups and finite Cay-DS groups. In particular we prove that a finite DS group is solvable, and every non-cyclic Sylow subgroup of a finite DS group is of order [Formula: see text], [Formula: see text], [Formula: see text] or [Formula: see text]. We also give several infinite families of non-Cay-DS solvable groups. In particular we prove that there exist two cospectral non-isomorphic [Formula: see text]-regular Cayley graphs on the dihedral group of order [Formula: see text] for any prime [Formula: see text].
Nonnoetherian geometry
Authors: Beil Charlie
Published: November 2015

We introduce a theory of geometry for nonnoetherian commutative algebras with finite Krull dimension. In particular, we establish new notions of normalization and height: depiction (a special noetherian overring) and geometric codimension. The resulting geometries are algebraic varieties with positive-dimensional points, and are thus inherently nonlocal. These notions also give rise to new equivalent characterizations of noetherianity that are primarily geometric. We then consider an application to quiver algebras whose simple modules of maximal dimension are one dimensional at each vertex. We show that the vertex corner rings of [Formula: see text] are all isomorphic if and only if [Formula: see text] is noetherian, if and only if the center [Formula: see text] of [Formula: see text] is noetherian, if and only if [Formula: see text] is a finitely generated [Formula: see text]-module. Furthermore, we show that [Formula: see text] is depicted by a commutative algebra generated by the cycles in its quiver. We conclude with an example of a quiver algebra where projective dimension and geometric codimension, rather than height, coincide.
Hierarchical Fuzzy Hidden Markov Chain for Web Applications
Authors: Sujatha R. , Rajalaxmi T. M.
Published: November 2015

Fuzzy sets, a scheme for handling nonstatistical vague concepts, provide a natural basis for the theory of possibility space. In this paper, on possibility space, a hierarchical generalization of the fuzzy hidden Markov chain (HFHMC) which is named as FHMC is proposed. For the proposed model, three problems which naturally arise in any kind of hidden Markov models (HMMs) are discussed. To solve these problems, generalized Baum–Welch and generalized Viterbi algorithms are formulated; further it is observed that the generalized Viterbi algorithm itself solves the first two problems namely the likelihood of a given observation sequence and finding the most likelihood state sequence, which exhibits that the time complexity involved in the computation of two problems reduces to a single problem. In order to ensure the ease of models use, the proposed model is applied to our institution website and simulation is performed to analyze the accessibility of the website among the users.