bluuebunny/crossref_metadata_2025 huggingface dataset:
London's Olympic Drug Testing Lab to Become National Phenome Center
Authors: Saini Angela
Published: August 2012

The U.K. Medical Research Council and the National Institute for Health Research will transform the Olympic antidoping laboratory into a national center dedicated to metabolic phenotyping.
Closing a Deadly Refuge
Authors: Roberts Leslie
Published: August 2012

On 17 July in the town of Gadap in Karachi, Pakistan, two gunmen shot at two men who were participating in a national polio vaccination campaign—sadly, a not uncommon occurrence.
Immunogenicity of a Monovalent Pandemic Influenza A H1N1 Virus Vaccine with or without Prior Seasonal Influenza Vaccine Administration
Authors: Igari Hidetoshi , Watanabe Akira , Segawa Shunsuke , Suzuki Akiko , Watanabe Mariko , Sakurai Takayuki , Watanabe Masaharu , Tatsumi Koichiro , Nakayama Mikio , Suzuki Kazuo , Sato Takeyuki
Published: August 2012

The immunogenicity of pandemic influenza A H1N1 virus (A/H1pdm) vaccine might be modified by prior seasonal trivalent influenza vaccine (sTIV) administration. We conducted a retrospective analysis of immunogenicity of 243 health care workers (number of sTIV-positive [sTIV+] subjects, 216; number of sTIV−subjects, 27) by hemagglutination inhibition. There was no significant difference in the ratios of antibody titers of ≥40 (41.2% versus 48.1%;P= 0.49) and fold increases in geometric mean titer (3.8 versus 4.5;P= 0.37). sTIV injected 7 to 10 days prior to A/H1pdm vaccine administration did not interfere with the immunogenicity of the latter.
Antibody in Middle Ear Fluid of Children Originates Predominantly from Sera and Nasopharyngeal Secretions
Authors: Kaur Ravinder , Kim Thomas , Casey Janet R. , Pichichero Michael E.
Published: August 2012

The human middle ear is devoid of any immunocompetent cells in normal mucosa. We sought to determine the source of antibody present in the middle ear of children. Total IgG, IgA, and secretory IgA antibodies were determined by enzyme-linked immunosorbent assay from the nasopharyngeal, middle ear, and serum samples of children with acute otitis media. The two-dimensional gel electrophoresis pattern of the entire array of IgA antibodies in the nasal wash (NW) and middle ear fluid (MEF) was compared from the MEF and NW samples using isoelectric focusing and Western blotting. The total IgG and IgA antibodies in the MEF and NW samples of 137 children were compared. The ratio of IgG to IgA in the MEF was significantly different (P< 0.008) compared to NW because IgA levels were higher and IgG levels lower in NW. The IgG/IgA ratio of MEF resembled serum consistent with transudation to the MEF. Small amounts of secretory IgA were detected in MEF but the electrophoresis patterns of the entire array of IgA antibodies in the MEF and NW were virtually identical in each child evaluated; thus, IgA in MEF derived predominantly from serum and the nasopharynx by reflux via the Eustachian tube. The IgG/IgA antibody levels in the MEF and the same composition of IgA antibody in the MEF and NW identifies the predominant source of antibody in the MEF as a transudate of serum combined with nasal secretions refluxed from the nasopharynx in children.
Genetic Characterization of Trichomonas vaginalis Isolates by Use of Multilocus Sequence Typing
Authors: Cornelius Denise C. , Robinson D. Ashley , Muzny Christina A. , Mena Leandro A. , Aanensen David M. , Lushbaugh William B. , Meade John C.
Published: August 2012

In this study, we introduce a multilocus sequence typing (MLST) scheme, comprised of seven single-copy housekeeping genes, to genetically characterize
Trichomonas vaginalis
. Sixty-eight historical and recent isolates of
T. vaginalis
were sampled from the American Type Culture Collection and female patients at area health care facilities, respectively, to assess the usefulness of this typing method. Forty-three polymorphic nucleotide sites, 51 different alleles, and 60 sequence types were distinguished among the 68 isolates, revealing a diverse
T. vaginalis
population. Moreover, this discriminatory MLST scheme retains the ability to identify epidemiologically linked isolates such as those collected from sexual partners. Population genetic and phylogenetic analyses determined that
T. vaginalis
population structure is strongly influenced by recombination and is composed of two separate populations that may be nonclonal. MLST is useful for investigating the epidemiology, genetic diversity, and population structure of
T. vaginalis
.
Prospective Evaluation of a Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry System in a Hospital Clinical Microbiology Laboratory for Identification of Bacteria and Yeasts: a Bench-by-Bench Study for Assessing the Impact on Time to Identification and Cost-Effectiveness
Authors: Tan K. E. , Ellis B. C. , Lee R. , Stamper P. D. , Zhang S. X. , Carroll K. C.
Published: August 2012

Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) has been found to be an accurate, rapid, and inexpensive method for the identification of bacteria and yeasts. Previous evaluations have compared the accuracy, time to identification, and costs of the MALDI-TOF MS method against standard identification systems or commercial panels. In this prospective study, we compared a protocol incorporating MALDI-TOF MS (MALDI protocol) with the current standard identification protocols (standard protocol) to determine the performance in actual practice using a specimen-based, bench-by-bench approach. The potential impact on time to identification (TTI) and costs had MALDI-TOF MS been the first-line identification method was quantitated. The MALDI protocol includes supplementary tests, notably for
Streptococcus pneumoniae
and
Shigella
, and indications for repeat MALDI-TOF MS attempts, often not measured in previous studies. A total of 952 isolates (824 bacterial isolates and 128 yeast isolates) recovered from 2,214 specimens were assessed using the MALDI protocol. Compared with standard protocols, the MALDI protocol provided identifications 1.45 days earlier on average (
P
< 0.001). In our laboratory, we anticipate that the incorporation of the MALDI protocol can reduce reagent and labor costs of identification by $102,424 or 56.9% within 12 months. The model included the fixed annual costs of the MALDI-TOF MS, such as the cost of protein standards and instrument maintenance, and the annual prevalence of organisms encountered in our laboratory. This comprehensive cost analysis model can be generalized to other moderate- to high-volume laboratories.
Cross-Species Transmission in the Speciation of the Currently Known Murinae-Associated Hantaviruses
Authors: Lin Xian-Dan , Wang Wen , Guo Wen-Ping , Zhang Xiao-He , Xing Jian-Guang , Chen Sheng-Ze , Li Ming-Hui , Chen Yi , Xu Jianguo , Plyusnin Alexander , Zhang Yong-Zhen
Published: August 2012

To gain more insight into the phylogeny of Dabieshan virus (DBSV), carried byNiviventer confucianusand otherMurinae-associated hantaviruses, genome sequences of novel variants of DBSV were recovered fromNiviventerrats trapped in the mountainous areas of Wenzhou, China. Genetic analyses show that all known genetic variants of DBSV, including the ones identified in this study, are distinct from otherMurinae-associated hantaviruses. DBSV variants show geographic clustering and high intraspecies diversity. The data suggest that DBSV is a distinct species in the genusHantavirus. Interestingly, DBSV shows the highest sequence identity to Hantaan virus (HTNV), with a >7% difference in the sequences of the N, GPC, and L proteins, whileN. confucianusis more closely related toRattus norvegicus(the host of Seoul virus [SEOV]) than toApodemus agrarius(the host of HTNV and Saaremaa virus [SAAV]). Further genetic analyses of all knownMurinae-associated hantaviruses (both established and tentative species) show that many of them, including DBSV, may have originated from host switching. The estimation of evolutionary rates and divergence time supports the role of cross-species transmission in the evolution ofMurinae-associated hantaviruses. The detection of positive selection suggests that genetic drift may contribute to the speciation ofMurinae-associated hantaviruses and that adaptation has a role as well.
Structural Basis for the Recognition of Lewis Antigens by Genogroup I Norovirus
Authors: Kubota Tomomi , Kumagai Akiko , Ito Hiromi , Furukawa Sanae , Someya Yuichi , Takeda Naokazu , Ishii Koji , Wakita Takaji , Narimatsu Hisashi , Shirato Haruko
Published: August 2012

Noroviruses (NoVs) bind to histo-blood group antigens, namely, ABH antigens and Lewis antigens. We previously showed the NoVs GI/2, GI/3, GI/4, and GI/8 were able to strongly bind to Lewis a (Le
a
) antigen, which is expressed by individuals who are nonsecretors. In this study, to investigate how Lewis antigens interact with GI NoV virion protein 1 (VP1), we determined the crystal structures of the P domain of the VP1 protein from the Funabashi 258 (FUV258) strain (GI/2) in complexes with Le
a
, Le
b
, H type 1, or A type 1 antigens. The structures were compared with those of the NV/68 strain (GI/1), which does not bind to the Le
a
antigen. The four loop structures, loop P, loop S, loop A, and loop B, continuously deviated by more than 2 Å in length between the Cα atoms of the corresponding residues of the FUV258 and NV/68 P domains. The most pronounced differences between the two VP1 proteins were observed in the structures of loop P. In the FUV258 P domain, loop P protruded toward the next protomer, forming a Le
a
antigen-binding site. The Gln389 residue make a significant contribution to the binding of the Le
a
antigen through the stabilization of loop P as well as through direct interactions with the α4-fucosyl residue (α4Fuc) of the Le
a
antigen. Mutation of the Gln389 residue dramatically affected the degree of binding of the Lewis antigens. Collectively, these results suggest that loop P and the amino acid residue at position 389 affect Lewis antigen binding.
Symmetry-Related Clustering of Positive Charges Is a Common Mechanism for Heparan Sulfate Binding in Enteroviruses
Authors: McLeish Nigel J. , Williams Çiğdem H. , Kaloudas Dimitrios , Roivainen Merja M. , Stanway Glyn
Published: August 2012

Coxsackievirus A9 (CAV9), a member of the
Picornaviridae
family, uses an RGD motif in the VP1 capsid protein to bind to integrin αvβ6 during cell entry. Here we report that two CAV9 isolates can bind to the heparan sulfate/heparin class of proteoglycans (HSPG). Sequence analysis identified an arginine (R) at position 132 in VP1 in these two isolates, rather than a threonine (T) as seen in the nonbinding strains tested. We introduced a T132R substitution into the HSPG-nonbinding strain Griggs and recovered infectious virus capable of binding to immobilized heparin, unlike the parental Griggs strain. The known CAV9 structure was used to identify the location of VP1 position 132, 5 copies of which were found to cluster around the 5-fold axis of symmetry, presumably producing a region of positive charge which can interact with the negatively charged HSPG. Analysis of several enteroviruses of the same species as CAV9,
Human enterovirus B
(HEV-B), identified examples from 5 types in which blocking of infection by heparin was coincident with an arginine (or another basic amino acid, lysine) at a position corresponding to 132 in VP1 in CAV9. Together, these data show that membrane-associated HSPG can serve as a (co)receptor for some CAV9 and other HEV-B strains and identify symmetry-related clustering of positive charges as one mechanism by which HSPG binding can be achieved. This is a potentially powerful mechanism by which a single amino acid change could generate novel receptor binding capabilities, underscoring the plasticity of host-cell interactions in enteroviruses.
Large-Scale Spatial and Temporal Genetic Diversity of Feline Calicivirus
Authors: Coyne Karen P. , Christley Rob M. , Pybus Oliver G. , Dawson Susan , Gaskell Rosalind M. , Radford Alan D.
Published: August 2012

Feline calicivirus (FCV) is an important pathogen of domestic cats and a frequently used model of human caliciviruses. Here we use an epidemiologically rigorous sampling framework to describe for the first time the phylodynamics of a calicivirus at regional and national scales. A large number of FCV strains cocirculated in the United Kingdom at the national and community levels, with no strain comprising more than 5% and 14% of these populations, respectively. The majority of strains exhibited a relatively restricted geographical range, with only two strains (one field virus and one vaccine virus) spreading further than 100 km. None of the field strains were identified outside the United Kingdom. Temporally, while some strains persisted locally for the majority of the study, others may have become locally extinct. Evolutionary analysis revealed a radial phylogeny with little bootstrap support for nodes above the strain level. In most cases, spatially and temporally diverse strains intermingled in the phylogeny. Together, these data suggest that current FCV evolution is not associated with selective competition among strains. Rather, the genetic and antigenic landscape in each geographical location is highly complex, with many strains cocirculating. These variants likely exist at the community level by a combination of
de novo
evolution and occasional gene flow from the wider national population. This complexity provides a benchmark, for the first time, against which vaccine cross-protection at both local and national levels can be judged.
Persistent Infection of Thymic Epithelial Cells with Coxsackievirus B4 Results in Decreased Expression of Type 2 Insulin-Like Growth Factor
Authors: Jaïdane Hela , Caloone Delphine , Lobert Pierre-Emmanuel , Sane Famara , Dardenne Olivier , Naquet Philippe , Gharbi Jawhar , Aouni Mahjoub , Geenen Vincent , Hober Didier
Published: August 2012

It has been hypothesized that a disturbance of central self-tolerance to islet β cells may play a role in the enteroviral pathogenesis of type 1 diabetes. Whether enteroviruses can induce an impaired expression of β-cell self-antigens in thymic epithelial cells has been investigated in a murine thymic epithelial (MTE) cell line. This cell line was permissive to the diabetogenic group B4 coxsackievirus (CV-B4) strain CV-B4 E2 and spontaneously expressed type 2 insulin-like growth factor (Igf2), the dominant self-antigen of the insulin family. In this model, a persistent replication of CV-B4 E2 was obtained, as attested to by the prolonged detection of intracellular positive- and negative-strand viral RNA by reverse transcription-PCR (RT-PCR) and capsid protein VP1 by immunofluorescent staining and by the release of infectious particles in culture supernatants. The chronic stage of the infection was characterized by a low proportion of VP1-positive cells (1 to 2%), whereas many cells harbored enteroviral RNA, as displayed by RT-PCR without extraction applied directly to a few cells.
Igf2
mRNA and IGF-2 protein were dramatically decreased in CV-B4 E2-infected MTE cell cultures compared with mock-infected cultures, whereas housekeeping and interleukin-6 (
Il6
) gene expression was maintained and
Igf1
mRNA was decreased, but to a lower extent. Inoculation of CV-B3, CV-B4 JVB, or echovirus 1 resulted in a low level of IGF-2 in culture supernatants as well, whereas herpes simplex virus 1 stimulated the production of the protein. Thus, a persistent infection of a thymic epithelial cell line with enteroviruses like CV-B4 E2 can result in a disturbed production of IGF-2, a protein involved in central self-tolerance toward islet β cells.
Circumventing Antivector Immunity by Using Adenovirus-Infected Blood Cells for Repeated Application of Adenovirus-Vectored Vaccines: Proof of Concept in Rhesus Macaques
Authors: Sun Caijun , Feng Liqiang , Zhang Yinfeng , Xiao Lijun , Pan Weiqi , Li Chufang , Zhang Linqi , Chen Ling
Published: August 2012

Adenovirus has been extensively exploited as a vector platform for delivering vaccines. However, preexisting antiadenovirus immunity is the major stumbling block for application of adenovirus-vectored vaccines. In this study, we found that freshly isolated peripheral blood mononuclear cells (PBMCs), mostly CD14
+
cells, from adenovirus serotype 5 (Ad5)-seropositive primates (humans and rhesus macaques) can be efficiently infected with Ad5
in vitro
. On the basis of this observation, a novel strategy based on
a
denoviral
v
ector-
i
nfected
P
BMC (AVIP) immunization was explored to circumvent antivector immunity. Autologous infusion of Ad5-SIVgag-infected PBMCs elicited a strong Gag-specific cellular immune response but induced weaker Ad5-neutralizing antibody (NAb) in Ad5-seronegative macaques than in macaques intramuscularly injected with Ad5-SIVgag. Moreover, Ad5-seropositive macaques receiving multiple AVIP immunizations with Ad5-SIVenv, Ad5-SIVgag, and Ad5-SIVpol vaccines elicited escalated Env-, Gag-, and Pol-specific immune responses after each immunization that were significantly greater than those in macaques intramuscularly injected with these Ad5-SIV vaccines. After challenged intravenously with a highly pathogenic SIVmac239 virus, macaques receiving AVIP immunization demonstrated a significant reduction in viral load at both the peak time and set-point period compared with macaques without Ad5-SIV vaccines. Our study warranted further research and development of the AVIP immunization as a platform for repeated applications of adenovirus-vectored vaccines.
Analysis of Epstein-Barr Virus-Regulated Host Gene Expression Changes through Primary B-Cell Outgrowth Reveals Delayed Kinetics of Latent Membrane Protein 1-Mediated NF-κB Activation
Authors: Price Alexander M. , Tourigny Jason P. , Forte Eleonora , Salinas Raul E. , Dave Sandeep S. , Luftig Micah A.
Published: August 2012

Epstein-Barr virus (EBV) is an oncogenic human herpesvirus that dramatically reorganizes host gene expression to immortalize primary B cells. In this study, we analyzed EBV-regulated host gene expression changes following primary B-cell infection, both during initial proliferation and through transformation into lymphoblastoid cell lines (LCLs). While most EBV-regulated mRNAs were changed during the transition from resting, uninfected B cells through initial B-cell proliferation, a substantial number of mRNAs changed uniquely from early proliferation through LCL outgrowth. We identified constitutively and dynamically EBV-regulated biological processes, protein classes, and targets of specific transcription factors. Early after infection, genes associated with proliferation, stress responses, and the p53 pathway were highly enriched. However, the transition from early to long-term outgrowth was characterized by genes involved in the inhibition of apoptosis, the actin cytoskeleton, and NF-κB activity. It was previously thought that the major viral protein responsible for NF-κB activation, latent membrane protein 1 (LMP1), is expressed within 2 days after infection. Our data indicate that while this is true, LCL-level LMP1 expression and NF-κB activity are not evident until 3 weeks after primary B-cell infection. Furthermore, heterologous NF-κB activation during the first week after infection increased the transformation efficiency, while early NF-κB inhibition had no effect on transformation. Rather, inhibition of NF-κB was not toxic to EBV-infected cells until LMP1 levels and NF-κB activity were high. These data collectively highlight the dynamic nature of EBV-regulated host gene expression and support the notion that early EBV-infected proliferating B cells have a fundamentally distinct growth and survival phenotype from that of LCLs.
Virome Analysis for Identification of Novel Mammalian Viruses in Bat Species from Chinese Provinces
Authors: Wu Zhiqiang , Ren Xianwen , Yang Li , Hu Yongfeng , Yang Jian , He Guimei , Zhang Junpeng , Dong Jie , Sun Lilian , Du Jiang , Liu Liguo , Xue Ying , Wang Jianmin , Yang Fan , Zhang Shuyi , Jin Qi
Published: August 2012

Bats are natural hosts for a large variety of zoonotic viruses. This study aimed to describe the range of bat viromes, including viruses from mammals, insects, fungi, plants, and phages, in 11 insectivorous bat species (216 bats in total) common in six provinces of China. To analyze viromes, we used sequence-independent PCR amplification and next-generation sequencing technology (Solexa Genome Analyzer II; Illumina). The viromes were identified by sequence similarity comparisons to known viruses. The mammalian viruses included those of the
Adenoviridae
,
Herpesviridae
,
Papillomaviridae
,
Retroviridae
,
Circoviridae
,
Rhabdoviridae
,
Astroviridae
,
Flaviridae
,
Coronaviridae
,
Picornaviridae
, and
Parvovirinae
; insect viruses included those of the
Baculoviridae
,
Iflaviridae
,
Dicistroviridae
,
Tetraviridae
, and
Densovirinae
; fungal viruses included those of the
Chrysoviridae
,
Hypoviridae
,
Partitiviridae
, and
Totiviridae
; and phages included those of the
Caudovirales
,
Inoviridae
, and
Microviridae
and unclassified phages. In addition to the viruses and phages associated with the insects, plants, and bacterial flora related to the diet and habitation of bats, we identified the complete or partial genome sequences of 13 novel mammalian viruses. These included herpesviruses, papillomaviruses, a circovirus, a bocavirus, picornaviruses, a pestivirus, and a foamy virus. Pairwise alignments and phylogenetic analyses indicated that these novel viruses showed little genetic similarity with previously reported viruses. This study also revealed a high prevalence and diversity of bat astroviruses and coronaviruses in some provinces. These findings have expanded our understanding of the viromes of bats in China and hinted at the presence of a large variety of unknown mammalian viruses in many common bat species of mainland China.
Increased Viral Loads and Exacerbated Innate Host Responses in Aged Macaques Infected with the 2009 Pandemic H1N1 Influenza A Virus
Authors: Josset Laurence , Engelmann Flora , Haberthur Kristen , Kelly Sara , Park Byung , Kawoaka Yoshi , García-Sastre Adolfo , Katze Michael G. , Messaoudi Ilhem
Published: August 2012

In contrast to seasonal influenza virus infections, which typically cause significant morbidity and mortality in the elderly, the 2009 H1N1 virus caused severe infection in young adults. This phenomenon was attributed to the presence of cross-protective antibodies acquired by older individuals during previous exposures to H1N1 viruses. However, this hypothesis could not be empirically tested. To address this question, we compared viral replication and the development of the immune response in naïve young adult and aged female rhesus macaques infected with A/California/04/2009 H1N1 (CA04) virus. We show higher viral loads in the bronchoalveolar lavage (BAL) fluid and nasal and ocular swabs in aged animals, suggesting increased viral replication in both the lower and upper respiratory tracts. T cell proliferation was higher in the BAL fluid but delayed and reduced in peripheral blood in aged animals. This delay in proliferation correlated with a reduced frequency of effector CD4 T cells in old animals. Aged animals also mobilized inflammatory cytokines to higher levels in the BAL fluid. Finally, we compared changes in gene expression using microarray analysis of BAL fluid samples. Our analyses revealed that the largest difference in host response between aged and young adult animals was detected at day 4 postinfection, with a significantly higher induction of genes associated with inflammation and the innate immune response in aged animals. Overall, our data suggest that, in the absence of preexisting antibodies, CA04 infection in aged macaques is associated with changes in innate and adaptive immune responses that were shown to correlate with increased disease severity in other respiratory disease models.
Severe Acute Respiratory Syndrome Coronavirus nsp1 Facilitates Efficient Propagation in Cells through a Specific Translational Shutoff of Host mRNA
Authors: Tanaka Tomohisa , Kamitani Wataru , DeDiego Marta L. , Enjuanes Luis , Matsuura Yoshiharu
Published: August 2012

Severe acute respiratory syndrome (SARS) coronavirus (SCoV) is an enveloped virus containing a single-stranded, positive-sense RNA genome. Nine mRNAs carrying a set of common 5′ and 3′ untranslated regions (UTR) are synthesized from the incoming viral genomic RNA in cells infected with SCoV. A nonstructural SCoV nsp1 protein causes a severe translational shutoff by binding to the 40S ribosomal subunits. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5′UTR of host mRNA. However, the mechanism by which SCoV viral proteins are efficiently produced in infected cells in which host protein synthesis is impaired by nsp1 is unknown. In this study, we investigated the role of the viral UTRs in evasion of the nsp1-mediated shutoff. Luciferase activities were significantly suppressed in cells expressing nsp1 together with the mRNA carrying a luciferase gene, while nsp1 failed to suppress luciferase activities of the mRNA flanked by the 5′UTR of SCoV. An RNA-protein binding assay and RNA decay assay revealed that nsp1 bound to stem-loop 1 (SL1) in the 5′UTR of SCoV RNA and that the specific interaction with nsp1 stabilized the mRNA carrying SL1. Furthermore, experiments using an SCoV replicon system showed that the specific interaction enhanced the SCoV replication. The specific interaction of nsp1 with SL1 is an important strategy to facilitate efficient viral gene expression in infected cells, in which nsp1 suppresses host gene expression. Our data indicate a novel mechanism of viral gene expression control by nsp1 and give new insight into understanding the pathogenesis of SARS.
Topiramate-induced refractive change and angle closure glaucoma and its ultrasound bimicroscopy findings
Authors: Saffra Norman , Smith Sanjay N , Seidman Carly Jane
Published: August 2012

Topiramate, a sulpha-based medication used in the treatment of migraine, has been documented as causing choroidal effusions, transient myopia and acute secondary angle closure glaucoma. We would like to report a case demonstrating these adverse effects and underscore the utility of ultrasound biomicroscopy in diagnosis and management.
Giant cell phlebitis: a potentially lethal clinical entity
Authors: Kunieda Takeshige , Murayama Masanori , Ikeda Tsuneko , Yamakita Noriyoshi
Published: August 2012

An 83-year-old woman presented to us with a 4-week history of general malaise, subjective fever and lower abdominal pain. Despite the intravenous infusion of antibiotics, her blood results and physical condition worsened, resulting in her sudden death. Autopsy study revealed that the medium-sized veins of the mesentery were infiltrated by eosinophil granulocytes, lymphocytes, macrophages and multinucleated giant cells; however, the arteries were not involved. Microscopically, venous giant cell infiltration was observed in the gastrointestinal tract, bladder, retroperitoneal tissues and myocardium. The final diagnosis was giant cell phlebitis, a rare disease of unknown aetiology. This case demonstrates for the first time that giant cell phlebitis involving extra-abdominal organs, including hearts, can cause serious morbidity.
A chemical analysis examining the pharmacology of novel psychoactive substances freely available over the internet and their impact on public (ill)health. Legal highs or illegal highs?
Authors: Ayres Tammy C , Bond John W
Published: August 2012

Objectives

Public Health England aims to improve the nation's health and acknowledges that unhealthy lifestyles, which include drug use, undermine society's health and well-being. Recreational drug use has changed to include a range of substances sold as ‘research chemicals’ but known by users as ‘legal highs’ (legal alternatives to the most popular illicit recreational drugs), which are of an unknown toxicity to humans and often include prohibited substances controlled under the Misuse of Drugs Act (1971). Consequently, the long-term effects on users' health and inconsistent, often illegal ingredients, mean that this group of drugs presents a serious risk to public health both now and in the future. Therefore, the aim of this study was to ascertain what is in legal highs, their legality and safety, while considering the potential impact, these synthetic substances might be having on public health.

Design

A total of 22 products were purchased from five different internet sites, 18 months after the UK ban on substituted cathinones, like mephedrone, was introduced in April 2010. Each substance was screened to determine its active ingredients using accepted analytical techniques.

Setting

The research was conducted in Leicestershire but has implications for the provision of primary and secondary healthcare throughout the UK.

Results

Two products, both sold as NRG-2 from different internet suppliers, were found to contain the banned substituted cathinones 4-methylethcathinone (4-MEC) and 4-methylmethcathinone (4-MMC), the latter being present in much smaller quantities. Although sold as research chemicals and labelled ‘not for human consumption’, they are thinly disguised ‘legal highs’, available online in quantities that vary from 1 g to 1 kg.

Conclusions

Despite amendments to legislation, prohibited class B substances are still readily available in large quantities over the internet. The findings suggest that these prohibited substances are being manufactured or imported into the UK on a large scale, which has serious implications for public health and clinicians who are ill equipped to deal with this newly emerging problem.
Prevalence and audiological features in carriers of GJB2 mutations, c.35delG and c.101T>C (p.M34T), in a UK population study
Authors: Hall Amanda , Pembrey Marcus , Lutman Mark , Steer Colin , Bitner-Glindzicz Maria
Published: August 2012

Objectives

To determine the carrier rate of the GJB2 mutation c.35delG and c.101T>C in a UK population study; to determine whether carriers of the mutation had worse hearing or otoacoustic emissions compared to non-carriers.

Design

Prospective cohort study.

Setting

University of Bristol, UK.

Participants

Children in the Avon Longitudinal Study of Parents and Children. 9202 were successfully genotyped for the c.35delG mutation and c.101>T and classified as either carriers or non-carriers.

Outcome measures

Hearing thresholds at age 7, 9 and 11 years and otoacoustic emissions at age 9 and 11.

Results

The carrier frequency of the c.35delG mutation was 1.36% (95% CI 1.13 to 1.62) and c.101T>C was 2.69% (95% CI 2.37 to 3.05). Carriers of c.35delG and c.101T>C had worse hearing than non-carriers at the extra-high frequency of 16 kHz. The mean difference in hearing at age 7 for the c.35delG mutation was 8.53 dB (95% CI 2.99, 14.07) and 12.57 dB at age 9 (95% CI 8.10, 17.04). The mean difference for c.101T>C at age 7 was 3.25 dB (95% CI −0.25 to 6.75) and 7.61 dB (95% CI 4.26 to 10.96) at age 9. Otoacoustic emissions were smaller in the c.35delG mutation carrier group: at 4 kHz the mean difference was −4.95 dB (95% CI −6.70 to −3.21) at age 9 and −3.94 dB (95% CI −5.78 to −2.10) at age 11. There was weak evidence for differences in otoacoustic emissions amplitude for c.101T>C carriers.

Conclusion

Carriers of the c.35delG mutation and c.101T>C have worse extra-high-frequency hearing than non-carriers. This may be a predictor for changes in lower-frequency hearing in adulthood. The milder effects observed in carriers of c.101T>C are in keeping with its classification as a mutation causing mild/moderate hearing loss in homozygosity or compound heterozygosity.
Inter-rater and test–retest reliability of quality assessments by novice student raters using the Jadad and Newcastle–Ottawa Scales
Authors: Oremus Mark , Oremus Carolina , Hall Geoffrey B C , McKinnon Margaret C ,   ECT & Cognition Systematic Review Team
Published: August 2012

Introduction

Quality assessment of included studies is an important component of systematic reviews.

Objective

The authors investigated inter-rater and test–retest reliability for quality assessments conducted by inexperienced student raters.

Design

Student raters received a training session on quality assessment using the Jadad Scale for randomised controlled trials and the Newcastle–Ottawa Scale (NOS) for observational studies. Raters were randomly assigned into five pairs and they each independently rated the quality of 13–20 articles. These articles were drawn from a pool of 78 papers examining cognitive impairment following electroconvulsive therapy to treat major depressive disorder. The articles were randomly distributed to the raters. Two months later, each rater re-assessed the quality of half of their assigned articles.

Setting

McMaster Integrative Neuroscience Discovery and Study Program.

Participants

10 students taking McMaster Integrative Neuroscience Discovery and Study Program courses.

Main outcome measures

The authors measured inter-rater reliability using κ and the intraclass correlation coefficient type 2,1 or ICC(2,1). The authors measured test–retest reliability using ICC(2,1).

Results

Inter-rater reliability varied by scale question. For the six-item Jadad Scale, question-specific κs ranged from 0.13 (95% CI −0.11 to 0.37) to 0.56 (95% CI 0.29 to 0.83). The ranges were −0.14 (95% CI −0.28 to 0.00) to 0.39 (95% CI −0.02 to 0.81) for the NOS cohort and −0.20 (95% CI −0.49 to 0.09) to 1.00 (95% CI 1.00 to 1.00) for the NOS case–control. For overall scores on the six-item Jadad Scale, ICC(2,1)s for inter-rater and test–retest reliability (accounting for systematic differences between raters) were 0.32 (95% CI 0.08 to 0.52) and 0.55 (95% CI 0.41 to 0.67), respectively. Corresponding ICC(2,1)s for the NOS cohort were −0.19 (95% CI −0.67 to 0.35) and 0.62 (95% CI 0.25 to 0.83), and for the NOS case–control, the ICC(2,1)s were 0.46 (95% CI −0.13 to 0.92) and 0.83 (95% CI 0.48 to 0.95).

Conclusions

Inter-rater reliability was generally poor to fair and test–retest reliability was fair to excellent. A pilot rating phase following rater training may be one way to improve agreement.
Measured natural periods of concrete shear wall buildings: insights for the design of Canadian buildings
Authors: Gilles Damien , McClure Ghyslaine
Published: August 2012

Structural engineers routinely use rational dynamic analysis methods for the seismic analysis of buildings. In linear analysis based on modal superposition or response spectrum approaches, the overall response of a structure (for instance, base shear or inter-storey drift) is obtained by combining the responses in several vibration modes. These modal responses depend on the input load, but also on the dynamic characteristics of the building, such as its natural periods, mode shapes, and damping. At the design stage, engineers can only predict the natural periods using eigenvalue analysis of structural models or empirical equations provided in building codes. However, once a building is constructed, it is possible to measure more precisely its dynamic properties using a variety of in situ dynamic tests. In this paper, we use ambient motions recorded in 27 reinforced concrete shear wall (RCSW) buildings in Montréal to examine how various empirical models to predict the natural periods of RCSW buildings compare to the periods measured in actual buildings under ambient loading conditions. We show that a model in which the fundamental period of RCSW buildings varies linearly with building height would be a significant improvement over the period equation proposed in the 2010 National Building Code of Canada. Models to predict the natural periods of the first two torsion modes and second sway modes are also presented, along with their uncertainty.
Pavement noise investigation on North Carolina highways: an on-board sound intensity approach
Authors: Wang George , Smith Gregory , Shores Richard
Published: August 2012

This paper presents the findings on tire–pavement noise on various types of pavements by using an on-board sound intensity (OBSI) method. Mitigation of traffic noise has become an increasingly important consideration for highway agencies when constructing new highways or improving the existing systems. As a competitive alternative for noise mitigation, quieter pavement may provide advantages that noise barriers do not have, or to where sound barriers are not suited. The first step in developing quieter pavement is identifying the noise levels of different types of highway pavements. To reach the ultimate goals of quieter pavement development, this research has focused on the most imperative task, i.e., to measure the noise levels of different types of pavements in North Carolina (NC). Pavement noise levels of 61 highway sites including 153 test sections around 30 counties for nine types of pavements across North Carolina have been investigated. A thorough literature review was conducted and OBSI testing equipment with sound intensity measuring process was established during this study. The results of OBSI data indicate that the tire–pavement noise levels of the six dense graded surface courses in NC are in a lower range, from 98.2 to 99.6 dBA, comparing with other dense graded surface friction courses in other states. The overall findings indicate that relatively quieter pavements have been used in North Carolina. The OBSI data collected will provide valuable information in future research for quieter pavement development and traffic noise management.
Comparative study of plastic property test methods for self-consolidating concrete
Authors: Shindman B. , Panesar D.K.
Published: August 2012

Currently, there are a variety of test methods to evaluate the plastic properties of self-consolidating concrete (SCC) specified in provincial, national, and international guidelines. There is, however, a dearth of knowledge on how the results of the various test methods compare with each other. Some of the tests are direct measures, others are indirect; some of the tests are qualitative and others are quantitative; and some tests have specified acceptance limits while others do not. The purpose of this study, initiated by the Ontario Ministry of Transportation (MTO), is to compare the plastic properties (filling ability, passing ability, and segregation resistance) of SCC and identify any correlations between them to determine the most appropriate test methods for evaluating the plastic properties of SCC. The filling ability (slump flow, L-box (t20 and t40), and V-funnel), passing ability (J-ring and L-box blocking ratio), and segregation resistance (visual stability index, column method, V-funnel (t5-t0)) tests are conducted on eight SCC mix designs. The results are compared to the acceptance criteria specified by the MTO for SCC. Based on the results, and their relationships, the plastic property tests most suitable for laboratory, prequalification, and field-testing are recommended.
ENDPOINT OF rp PROCESS USING RELATIVISTIC MEAN FIELD APPROACH AND A NEW MASS FORMULA
Authors: LAHIRI CHIRASHREE , GANGOPADHYAY G.
Published: August 2012

Densities from relativistic mean field calculations are applied to construct the optical potential and, hence calculate the endpoint of the rapid proton capture (rp) process. Mass values are taken from a new phenomenological mass formula. Endpoints are calculated for different temperature-density profiles of various X-ray bursters. We find that the rp process can produce significant quantities of nuclei upto around mass 95. Our results differ from existing works to some extent.
EMPIRICAL COMPARISON OF METHODS FOR THE HIERARCHICAL PROPAGATION OF HYBRID UNCERTAINTY IN RISK ASSESSMENT, IN PRESENCE OF DEPENDENCES
Authors: PEDRONI NICOLA , ZIO ENRICO
Published: August 2012

Risk analysis models describing aleatory (i.e., random) events contain parameters (e.g., probabilities, failure rates, …) that are epistemically-uncertain, i.e., known with poor precision. Whereas aleatory uncertainty is always described by probability distributions, epistemic uncertainty may be represented in different ways (e.g., probabilistic or possibilistic), depending on the information and data available.

The work presented in this paper addresses the issue of accounting for (in)dependence relationships between epistemically-uncertain parameters. When a probabilistic representation of epistemic uncertainty is considered, uncertainty propagation is carried out by a two-dimensional (or double) Monte Carlo (MC) simulation approach; instead, when possibility distributions are used, two approaches are undertaken: the hybrid MC and Fuzzy Interval Analysis (FIA) method and the MC-based Dempster-Shafer (DS) approach employing Independent Random Sets (IRSs). The objectives are: i) studying the effects of (in)dependence between the epistemically-uncertain parameters of the aleatory probability distributions (when a probabilistic/possibilistic representation of epistemic uncertainty is adopted) and ii) studying the effect of the probabilistic/possibilistic representation of epistemic uncertainty (when the state of dependence between the epistemic parameters is defined).

The Dependency Bound Convolution (DBC) approach is then undertaken within a hierarchical setting of hybrid (probabilistic and possibilistic) uncertainty propagation, in order to account for all kinds of (possibly unknown) dependences between the random variables.

The analyses are carried out with reference to two toy examples, built in such a way to allow performing a fair quantitative comparison between the methods, and evaluating their rationale and appropriateness in relation to risk analysis.
A GENETIC PROGRAMMING-BASED LEARNING ALGORITHMS FOR PRUNING COST-SENSITIVE CLASSIFIERS
Authors: NIKDEL ZAHRA , BEIGY HAMID
Published: August 2012

In this paper, we introduce a new hybrid learning algorithm, called DTGP, to construct cost-sensitive classifiers. This algorithm uses a decision tree as its basic classifier and the constructed decision tree will be pruned by a genetic programming algorithm using a fitness function that is sensitive to misclassification costs. The proposed learning algorithm has been examined through six cost-sensitive problems. The experimental results show that the proposed learning algorithm outperforms in comparison to some other known learning algorithms like C4.5 or naïve Bayesian.
A MULTI-COLONY ANT SYSTEM FOR COMBINATORIAL OPTIMIZATION PROBLEM
Authors: WANG RONG-LONG , ZHOU XIAO-FAN , ZHAO LI-QING , XIA ZE-WEI
Published: August 2012

A multi-colony ant system (MAS) is proposed for the combinatorial optimization problems. The proposed MAS is inspired by the knowledge that there are many colonies of ants in the natural world and organized with multiple colonies of ants. At first, ants perform solution search procedure by cooperating with each other in the same colony until no better solution is found after a certain time period. Then, communication between different colonies is performed to build new pheromone distributions for each colony, and ants start their search procedure again in each separate colony, based on the new pheromone distribution. The proposed algorithm is tested by simulating the traveling salesman problem (TSP). Simulation results show that the proposed method performs better than the traditional ACO.
A COMPARISON OF MATHEMATICAL AND ARTIFICIAL NEURAL NETWORK MODELING FOR ROSA PETALS USING HOT AIR DRYING METHOD
Authors: BANAKAR AHMAD , KARIMI AKANDI S. R.
Published: August 2012

Damask rose (scientific name: Rosa damascene) belongs to the Rosaceae family and is valuable in medicine. In this study, the influence of air temperature and velocity are investigated on hot air dryer of the rose petals. Artificial drying of the agricultural products is one of the most common maintenance procedures. Suitable drying methods reduce the waste and damage during the storage and save the quality of the products. Optimization and control of the drying process is also based on the precise modeling. Here, moisture ratio was estimated at any temperature and air velocity by mathematical models. Later, artificial networks including feed-forward and recurrent network were applied to predict the moisture ratio via temperature, air velocity and time. The obtained results show that neural network is the best for modeling; nevertheless, the recurrent network has the best performance in predicting the moisture ratio.
Hormonal Interactions in the Regulation of Plant Development
Authors: Vanstraelen Marleen , Benková Eva
Published: August 2012

Plants exhibit a unique developmental flexibility to ever-changing environmental conditions. To achieve their profound adaptability, plants are able to maintain permanent stem cell populations and form new organs during the entire plant life cycle. Signaling substances, called plant hormones, such as auxin, cytokinin, abscisic acid, brassinosteroid, ethylene, gibberellin, jasmonic acid, and strigolactone, govern and coordinate these developmental processes. Physiological and genetic studies have dissected the molecular components of signal perception and transduction of the individual hormonal pathways. However, over recent years it has become evident that hormones do not act only in a linear pathway. Hormonal pathways are interconnected by a complex network of interactions and feedback circuits that determines the final outcome of the individual hormone actions. This raises questions about the molecular mechanisms underlying hormonal cross talk and about how these hormonal networks are established, maintained, and modulated throughout plant development.
Climate and Water: Knowledge of Impacts to Action on Adaptation
Authors: Kiparsky Michael , Milman Anita , Vicuña Sebastian
Published: August 2012

As adaptation becomes more tightly integrated into the range of responses to climate change, understanding how knowledge of climate change impacts and vulnerabilities can be effectively used is essential both to direct research and to support action. This article reviews literature along an intellectual transect from knowledge of climate impacts on water systems to the influence of that knowledge on adaptation responses. We discuss scientific evidence for changing hydroclimatic regimes, methods for translating climatic information into results relevant to adaptation, uncertainties in these results, methods for addressing uncertainty via adaptation processes, challenges and opportunities for knowledge development and transfer, and sociopolitical factors that enable or hinder the use of knowledge. Challenges remain in developing and applying methods for identifying and reducing underlying vulnerabilities and reliably connecting technical knowledge of climate impacts with local needs remains an unsolved problem. But new decision-making methods and the potential to learn from analogous water management situations provide hope for near-term progress.